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Article type: Cover
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Cover1-
Published: September 10, 1980
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Article type: Appendix
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App1-
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Article type: Appendix
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App2-
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Article type: Index
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A1-A10
Published: September 10, 1980
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Article type: Index
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A11-A21
Published: September 10, 1980
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Article type: Appendix
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Yasuhiro Kojima, Natsuki Kato, Yukimasa Terada
Article type: Article
Session ID: 1
Published: September 10, 1980
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I. 1.1-t-Butyl-7-hydroxy perhydrofuro [2,3-b] furan 1 which was selected asamodel compound about the antifeeding active center of the neo-clerodane diterpenes and that was synthesized via a furan-alcohol which was derived by a coupling reaction with an epoxide and Li di(3-furyl)cuprate. Although 1 of diastereomeric mixture could not separated on TLC etc., its lactone derivative gave lactone a and b as a fine crystal. Configurations of their H^1 protons could not determined from the nmr spectra, since their coupling constants had approximately the same values to each others. Then we decided successfully the configuration of the protons and the conformation of the compounds by the combination of the LIS experiments (LIS) and the empirical force-field calculation (EFF). I. 2. We reported that the synthesis of the clerodin homologue 3 for investigation of the structure-activity relationship. However, it was very difficult to determine the C^<11> configuration on the epoxy-acetonide 8 of the synthetic intermediate. Thus, we synthesized the diastereomeric hydroxy-acetonide A (9) and B (10) via an epoxidation reaction by mCPBA or NBS. Each C^<11> configuration of the derivatives was determined by the EFF-LIS combination method, as well as lactone a and b, as shown in Fig. 2. II. Mono and disubstituted benzene derivatives were synthesized for clarifing the stabilization of the perhydrofuro[2,3-b]furan ring by steric effect. It is noteworthy that the furo-furan derivative from sym-m-xylenol detected as a 1: 1 mixture of 4 and 11+12 on NMR, whereas ca. 90% amounts of dimethyl benzene derivative 18 existed in the perhydrofuro[2,3-b]furan ring form.
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T. Sato, T. Kawara, M. Kawashima, A. Noda, K. Naruse, T. Fujisawa
Article type: Article
Session ID: 2
Published: September 10, 1980
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The regioselective ring cleavage of β-propiolactone was established by the use of diorganocuprates or Grignard reagents in the presence of a copper(I) catalyst to afford β-substituted propionic acids in high yields. The reaction provides a useful method for three carbon homologation terminating with a carboxyl function, and can be used for the synthesis of several natural products. For the synthesis of a macrolide, a copper catalyzed reaction of β-propiolactone with 12-methoxydodecanylmagnesium bromide (2), which was derived from available 1,12-dodecanediol, was used to construct 15-methoxypentadecanoic acid (3), which was easily converted into exaltolide (5). One-pot synthesis of cis-4-alkenoic acids, which are known as a component of perfumes and flavors, was achieved by the reaction of β-propiolactone with cis-1-alkenylcuprates prepared form Grignard reagents, copper(I) iodide and acetylene. Among them, cis-4-heptenoic acid was easily transformed into cis-jasmone (11) via cis-8-undecen-2,5-dione (10). β-Methyl-β-propiolactone was used as an important component for the terpene synthesis. Homoprenyl Grignard reagent reacted with the lactone in the presence of a copper(I) catalyst to afford citronellic acid (12), which was converted into various monoterpenes, such as citronellol, geraniol (14) and nerol (15). Further, by utilizing the SN2 type of ring-opening reaction of (R)-β-methyl-β-propiolactone, which was easily obtained from (S)-(+)-3-bromobutyric acid resolved by an optically active amine, (S)-ar-turmerone (18) was synthesized in high enantiomeric excess.
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Yukio Masaki, Kazuhiko Sakuma, Kinji Hashimoto, Kenji Kaji
Article type: Article
Session ID: 3
Published: September 10, 1980
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Biologically active linear degraded terpenoids, a diol component (1a) of the pheromonal secretion of the queen butterfly and ω-quinoid hexenoic acid (2a), a final metabolite of ubiquinones were synthesized from easily accessible isoprenoids (7) by a new regio- and stereo-selective method in which facile functionalizations of the isopropylidene terminus of isoprenoids and a novel anionic [2,3]-sigmatropic rearrangement accomponied by sulfur extrusion are involved. By the method the degraded β-farnesene (4) was also synthesized. The synthetic sequence is featured by two stages. At first the acetic acid moiety was introduced as the substituent on sulfur into the isoprenoid skeleton to give regiospecifically the terminal allylic sulfides (9) by the following methods, one involves addition of the sulfenyl chloride (6) derived from methyl thioglycolate to isoprenoids (7) followed by mild dehydrochlorination and the other involves treatment of (7) with SO_2Cl_2 providing the allylic chlorides (10) which was then treated with methyl thioglycolate in the presence of base. Secondly treatment of (9) with strong base such as t-BuOK or NaH in DMSO resulted in an unique one-pot desulfurizative [2,3]-sigmatropic rearrangement to transfer stereoselectively the acetic acid moiety onto the terminal allylic position of the isoprenoid skeleton yielding the sulfur-free ester (13).
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M. Ito, A. Kodama, K. Tsukida, H. Matsumoto, S. Kawamura, O. Muto, T. ...
Article type: Article
Session ID: 4
Published: September 10, 1980
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Retro-γ-retinal, possessing the dissected diene and trienal groups, has been investigated as a new chromophore in rhodopsin analogues. The syntheses and spectral properties of the three retro-γ-retinal isomers [all-trans(VIIa), 11-cis(VIIa') and 9-cis(VIIb)] have been described. Of these three isomers, (VIIb) has given a new artificial visual pigment, 9-cis-retro-γ-rhodopsin (VIIIb)[λ_<max>=420 nm]. From the results of the photochemical reaction of (VIIIb) at a liquid nitrogen temperature, it has been infered that the formation of bathorhodopsin is due to the photoisomerization of the chromophore in the rhodopsin molecule and is not attributed to the translocation of a proton from C-4〜C-8 to the Schiff-base nitrogen in the retinylidene chromophore.
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Hiroyuki Akita, Koji Nakanishi
Article type: Article
Session ID: 5
Published: September 10, 1980
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The crucial primary step in visual transduction is known to be the 11-cis to trans isomerization of the rhodopsin chromophore, which is the protonated Schiff base of 11-cis retinal. Four retinoids 1-4 in which the 11-ene bond is locked into 11-cis geometry by virtue of their cycloheptatrienylidene moieties have been synthesized; these four molecules correspond to 11-cis, 11,13-dicis, 9,11-dicis, and 9,11,13-tricis retinals. All four have been found to bind to cattle opsin to form the corresponding rhodopsin analogs. These pigments, while retaining the full chromophore, are nonbleachable when exposed to light corresponding to their absorption maxima. These studies show that retinals locked into the 11-cis geometry by 7-membered rings undergo no photoisomerization and block the bleaching of visual pigments; namely an 11-cis to trans isomerization is a prerequisite for visual transduction.
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K. MORI, T. SUGURO, S. MASUDA, H. UEDA, T. NUKADA, T. EBATA
Article type: Article
Session ID: 6
Published: September 10, 1980
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Our recent syntheses of chiral insect pheromones have enabled us to recognize the importance of absolute stereochemistry in determining pheromone activity. In order to carry out accurate bioassays, we must synthesize optically pure pheromones in sufficient quantities. Herein we give three examples of such chiral syntheses. 1) (3S, 11S)-29-Hydroxy-3,11-dimethylnonacosan-2-one 1. This is the pheromone of the German cockroach, Blattella germanica. (R)-(+)-Citronellic acid was the starting material. 2) Methyl (R, E)-tetradeca-2,4,5-trienoate 27. This is the pheromone of the dried bean beetle, Acanthoscelides obtectus. The synthesis started from (R)-undec-1-yn-3-ol which was obtained by conventional resolution. 3) (S)-Sulcatol 35a. This is the pheromone of Gnathotrichus retusus. The crucial step was the yeast reduction of ethyl acetoacetate.
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K. Kon, S. Isoe
Article type: Article
Session ID: 7
Published: September 10, 1980
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I. Tricyclo[3,3,0,0^<2,8>]octanones as Building Blocks in Natural Products Synthesis: Synthesis of Chrysomelidial and Dehydrologanin Aglycone. Tricyclo[3,3,0,0^<2,8>]octanone was transformed with formic acid or p-toluenesulfonic acid into functionalized bicyclo[3,3,0]octanone, which has a distinguishable functional group in each five membered ring and can be led into cyclopentanoid natural products via the selective conversion of the functional group. We have applied this versatile intermediate towards some of the cyclopentanoid monoterpens. II. Synthetic Study of Optical Active Quadrone In 1978 R. L. Ranieri and G. J. calton described the isolation and characterization of an antineoplastic agent, quadrone; a substance which possesses a highly compacted tetracyclic structure and exhibits cytotoxic activity. Herein, we described synthetic approach to quadrone from optical active monoterpen, fenchone.
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A. Murai, S. Sato, H. Taketsuru, K. Takahashi, T. Masamune
Article type: Article
Session ID: 8
Published: September 10, 1980
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The title compounds are representative members of sesquiterpenoid phytoalexins isolated from diseased Solanceae plants. These compounds are characterized structurally by the presence of five or six asymmetric centers in two ten-carbon skeletons, spiro[4,5]decane and perhydronaphthalene, as well as by different stereochemistry at C-4 and C-5 from natural usual sesquiterpenes. We describe herein stereoselective syntheses of these compounds. The process leading to the synthesis of oxygenated spirovetivanes (2〜5) consists of two major steps; (i) synthesis of norsolavetivone (8) starting from orcinol dimethyl ether (9) (Scheme 1) and (ii) regio- and stereoselective introduction of nucleophile(s) into C-10 followed by conversion into lubimin (2) and related compounds and (3 and 21) (Scheme 3). Transformation into oxylubimin (3) from 8 essentially in the same manner is under investigation. On the other hand, the process aimed at the synthesis of capsidiol (6) is summarized in Scheme 6, resulting in preparation of epoxy diene (24). Transformation of 24 into 2 by π-cyclization is also under investigation.
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Haruhisa Shirahama, Kazuya Sakai, Toshikazu Ohtsuka, Shyunziro Misumi, ...
Article type: Article
Session ID: 9
Published: September 10, 1980
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Two pentalenanoids, pentalenene (4) and pentalenic acid (5) were synthesized from humulene via biosynthetic pathway. Humulene on treatment with Hg(NO_3)_2 followed by KBr gave 10-bromomercuri-3,6-secoprotoilludane derivatives 12 and 13 and these on demercuration or under Whitesides's reaction conditions (O_2, NaBH_4, DMF) furnished the ethers, 9 and 10, or hydroxy ethers, 14, 15, 17 and 18, respectively. Cleavage of ether linkage in these compounds resulted in the formation of 3,6-secoprotoilluden-3-ol (11) or 3,10-diol (16) depending upon the starting ethers. These two compounds, 11 and 16, which are equivalent to cation 3 and the corresponding cation with hydroxyl group at C-10, are the key intermediates not only in the chemical synthesis but also in the biosynthesis of pentalenanoids. Pentalenene (4) was obtained by the formolysis of 11 while a corresponding compound with hydroxyl group at C-10, 24, was furnished by the treatment of 16 with BF_3-OEt_2. The allylic oxidation of 13-Me of 24 yielded methyl pentalenate (29). The compound 11 was converted to methoxy ketone 31 which was expected to serve as the intermediate for the synthesis of pentalenanoids with a lactone moiety in ring C through the enone 33 as shown in Fig 5. We have already obtained 39 and 41 from which the syntheses of pentalenolactone E, G and H are in progress.
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T. Satoh, S. Takita, N. Tamura, K. Yamakawa
Article type: Article
Session ID: 10
Published: September 10, 1980
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Stereochemical study on the angular hydroxylation of polycyclic ketones using benzeneseleninic anhydride and its application to the total synthesis of furanoeremophilanes are described. Introduction of a hydroxyl group to the tertiary carbon of simple ketones (8-10), furanoeremophilane-type ketones (16-20) was accomplished by the use of benzeneseleninic anhydride. 10β-Hydroxy compounds were obtained in the case of 16-18. 10α-Hydroxy compounds were obtained in the case of 19 and 20. In the hydroxylation reaction of polycyclic ketones using benzeneseleninic anhydride, the results suggest that the thermodynamically more stable product was usually produced as the major products. Deketalization of 10α-hydroxy compound 22b followed by acetylation gave triketo-acetate (37). Thioketalization of 37 followed by treatment with K_2CO_3 afforded 39b. Desulfurization of 39b gave a mixture of 40 and dehydro product (41) in 90% yield. The mixture was reduced with Pd-C to give 40 quantitatively. Dehydration of 40 with SOCl_2 followed by reduction with NaBH_4 gave (±)-43a. (±)-Adenostylone (43b), (±)-decompositin (4), and (±)-tetrahydro-decompositin (44) were synthesized from (±)-43a in a good yield, respectively. 3β-Propionyloxy compound (45b), which was derived from 29, was treated with benzeneseleninic anhydride to give 10β-hydroxy compound (46a) and 10α-hydroxy compound (46b). (±)-3β,6β-Dipropionyloxy-euryopsin-9-one (48b) was synthesized from the hydroxy compound (46b) in three steps.
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S. Inayama, H. Hori, T. Ohsaka, N. Shimizu, T. Shibata, T. Kawamata, Y ...
Article type: Article
Session ID: 11
Published: September 10, 1980
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Eudesmanolides (1, 17) was subjected to a novel skeletal-cyclization rearrangement to trimethylethanoadamantanone (2) using hot phosphoryl chloride. When the reaction product was treated with hot aqueous sodium hydroxide, new epoxytricycloeudesmanone (5) and tricycloeudesmendiones (6, 7) were isolated in addition to the epoxy ketone (4). The absolute stereostructures of 5, 6 and 7 were determined by spectrometric and X-ray crystallographic methods. Tricycloeudesmenones (8, 9) as the main product in the aforementioned reaction were neatly separated through the reoxidation of their alcohol derivatives (10, 11), and well characterized by correlating 8 and 9 with 4, 5, 6, and 7. A unique structure of the byproduct (12) obtained besides 10 and 11 on LiAlH_4 reduction of 8 and 9 was also elucidated. The proposed reaction pathway from 1 to 2 through carboxyeudesmene intermediates and the key intermediate tricycloeudesmenones (8, 9) was rationalized on the basis of acid catalized rearrangement experiments and the force field calculation for possible candidate intermediates (8, 9 to 2) created by using a computer technique.
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M. Tada, Y. Sugimoto, M. Nomura, T. Takahashi
Article type: Article
Session ID: 12
Published: September 10, 1980
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Some sesquiterpene lactones and furans with a perhydronaphtho-furan ring system, furanoeremophilanes and eudesmanolides, have been synthesized by a route involving alkylation of 2,4-dimethyl-3-furoic acid and 2-methyl-3-furoic acid. 1) Reaction of a dianion (D) generated from 2,4-dimethyl-3-furoic acid with 2-methyl-3-methoxy-2-cyclohexenone gave an acid (11). Acid-catatyzed cyclization of dihydro acid (12), obtained by hydrogenation of 11, yielded a diketone (13) stereoselectively. Furanoeremophilane-3,6-dione (3) and furanoeremophilan-14,6α-olide (4) were synthesized in 5 steps from the diketone (13), respectively. 2) Similar alkylation reaction of 2-methyl-3-furoic acid with 3-methoxy-2-cyclohexenone gave an acid (23). A diketone (25) was obtained by reaction of methyl ester (24) of 23 with LiMe_2Cu. Oxidation of furans with peracid to create γ-lactones was investigated. 13-Nordihydrocallitrisin (5a) was synthesized from 27.
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M. Niwa, Y. Terada, M. Iguchi, S. Yamamura
Article type: Article
Session ID: 13
Published: September 10, 1980
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From a biogenetic point of view, many sesquiterpenes are considered to be derived from germacrenes or germacrones as an important precurser, and their conformations have been discussed in connection with their transannular reactions as well as with thermal isomeizations. Thus, molecular mechanics calculations were successfully carried out to evaluate relative stabilities of each conformation of several germacrenes in their ground states and transition states. Particularly, molecular mechanics calculation was carried out successfully in the case of thermal reaction of acoragermacrone, and also attempted for the acid-catalyzed reaction of preisocalamendiol leading to the formation of isocalamendiol, although the result so far obtained was not necessarily satisfied. On the basis of the above results, acid and base-catalyzed reactions of epoxygermacrene-D were carried out to give many interesting compounds similar to oppositol, axisonitrile-1, periplanone-A, junenol and so on. Reaction process of these compounds is also presented.
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Michiharu Kato, Kiyoshi Heima, Yukio Matsumura, Akira Yoshikoshi
Article type: Article
Session ID: 14
Published: September 10, 1980
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Starting from the known keto ester (3), the total synthesis of siccanin (1), a strongly antigerminative mold metabolite produced by Helminthosporium siccans, as well as siccanochromene-E (2), one of biogenetic congeners of the former, has been achieved. The keto ester (3) was submitted to the Robinson annulation with butenone to yield octalone (5), which was then converted into the octaline (8) through the 5-step conventional sequence shown in Scheme 1. After deacetalization of (8), the resultant octalone (10) was isomerized to conjugated enone (11) by treatment with p-toluene-sulfonic acid in methanol, and the latter enone was proven cis-fused by physical and chemical means (Scheme 2). Regioselective hydroxymethylation of the kinetic enolate of 11, followed by methylation with methyl lithium afforded carbinol (25), which was then converted to aldehyde (27) in moderate overall yield (Scheme 3). Diol (28) obtained from 27 in the reaction with lithiated orcinol dimethyl ether yielded, on treatment with pyridinium hydrochloride, tetrahydrofuran derivative (29) in high yield, and the product was then demethylated to monomethyl ether (30) (Scheme 4). While sulfuric acid-induced cyclization of 30 afforded siccanochromene-E methyl ether (31), Lewis acid-catalyzed reaction of 30 gave siccanin methyl ether (32) along with other unidentified products. Demethylation of 32 and 31 were achieved by treatment with sodium ethylthiolate to give 1 and 2 in good yield, respectively (Scheme 5).
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Isao Kitagawa, Hirotaka Shibuya, Hiromichi Fujioka, Shinji Tsujii, Aki ...
Article type: Article
Session ID: 15
Published: September 10, 1980
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In the course of synthetic studies on the taxane-type diterpenes, we have been working on the synthesis of optically active taxa-4(16),11-diene deriv.(2). In this paper, our effort for construction of the target structure via combination of segments A (22) and B [(-)-30] is presented. I. Structure Elucidation of 1,1,3-Trimethylcyclohexane Deriv. (5) The structure of 5, the staring material for segment A (22), which was prepared from 1,2,2-trimethylcyclopentane deriv. (4) by use of TBCO via the ring-enlargement reaction, has been elucidated by converting to the ketone (10) via 7, 8, and 9. II. Synthesis of Segment A (22) The allyl alcohol (14), prepared from 5 via 11, 12, and 13, was converted to sec. alcohol (15) by acetylation and SeO_2 oxidation. 15 was then converted via 16 and 17 to 18, which, under basic conditions, was converted to two diastereomers (19, 20). 20, having the C-6 configuration same as the natural taxanes, was converted smoothly to opt. active allyl chloride (22). III. Synthesis of Segment B [(-)-30] Optical resolution of the cyclopropane deriv. (24) was accomplished via HPLC separation of the (+)-(2S,3S)-2,3-butanediol deriv. (25) to furnish (-)-26 and (+)-26. (-)-26 was then converted to the opt. active sulfone [(-)-30] via 27, 28, and 29. IV. Synthesis of Taxa-4(16),11-diene Deriv. (2) Coupling of 22 with (-)-30 was effected by use of t-BuLi to give 31. 31 was then converted to 36 via 32, 33, and bissulfides (34, 35). Derivation of 36 and its deriv. leading to 2 is under study and the results will be discussed.
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M. Ohmori, K. Nakayama, S. Yamada, H. Takayama
Article type: Article
Session ID: 16
Published: September 10, 1980
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A convenient and stereoselective synthetic method of vitamin D_3 metabolites having a chiral center on the side chain, has been deviced using chirality transfer method. In this method, the target molecule is constructed from two parts, namely, steroid skeleton and the side chain. The C-22 steroid alcohol(6a), which was conveniently obtained from ergosterol by Barton's method, was chosen as a common precursor of steroid skeleton and was used after being converted to the phenylsulfonyl derivative(6d). As a precursor of the side chain, the appropriate natural chiral molecule with desired stereochemistry was chosen. Applying this method, (24R)-24,25-dihydroxyvitamin D_3(1) was synthesized stereoselectively and efficiently (in 17% overall yield from 6d) using D-glyceric acid as a chiral synthon to construct the side chain. Synthesis of (25R)-25,26-dihydroxyvitamin D_3(2) was also examined and was partially achieved employing the same steroid precursor(6d) as used in the synthesis of 1 and citramalic acid as a precursor of the side chain.
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N. Ikekawa, M. Ishiguro, M. Morisaki, Y. Hirano, J. Oshida, S. Takatsu ...
Article type: Article
Session ID: 17
Published: September 10, 1980
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Stereoselective syntheses of some biological active steroids having functional groups in their side chain have been investigated. Brassinolide (A), a new plant growth promoter isolated from rape pollen, was synthesized from bisnorcholenic aicd. The 22R-hydroxy-23R, 24R-epoxide (6) was obtained by Sharpless oxidation of cis-allylic alcohol (5). A nitrile group, which was subsequently transformed to methyl group via aldehyde, was introduced at C-24 position by hydrocyanation. The side chain having same stereochemical configuration was thus obtained. After introduction of 6-ketone and 2α, 3α-diol groups, Baeyer-Villiger oxidation gave the lactone 16, which was converted to A, mp 273-278 (decomp). The IR, MS and ^<13>C-n.m.r spectra are in good agreement with those of the natural one. Calcidiol lactone (B), a new metabolite of vitamin D_3, has also synthesized from the 22-aldehyde 2. Reaction with vinylmagnesium bromide afforded the (22R)-22-alcohol 17 predominantly. By the Claisen rearrangement of 17 with orthopropionate gave the 26-ester 18. Iodolactonization of 18 yielded regio- and stereoselctively a single product 19, which was led to the lactone 20. The C-23 configuration of the lactone was determined as R by transformation into 22- and 23-hydroxycholesterols. Introduction of a hydroxyl at C-25 was achieved by oxidation with MoOPH. The hydroxylactone 25 was converted to (23R)-calcidiol lactone. The UV and MS spectra of the synthetic compound were identical with those of the metabolite. The iodolactonization was applied to the stereoselective synthesis of antheridiol (C). The 24-isopropyl-26-ester (32) was transformed to 22,23-epoxy-26-ester (32) via iodolactone 31. The epoxide 32 was converted to the 22-hydroxy-γ-lactone 34, possessing the same stereochemical configuration as that of natural antheridiol.
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T. Takahashi, T. Nagashima, H. Ikeda, I. Minami, J. Tsuji
Article type: Article
Session ID: 18
Published: September 10, 1980
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We report here a simple synthetic method for macrocyclic ketones based on intramolecular alkylation of carbanion, generated from protected cyanohydrin. Subsequent mild treatment with acid and base of the cyclized products leads to macrocyclic ketones in high yields. The present method of alkylation can generate mono-carbanion easily and the reaction is rapid and irreversible, and hence requires short reaction time. This method was successfully applied to the synthesis of trans-2-cyclopentadecenenone 15 as a precursor of (±)-Muscone and Exaltone. As synthetic targets of keto lactones, we synthesized the naturally occurring Zearalenone and trans-Resorcilide. Zearalenone was also prepared in high yield by intramolecular alkylation of dianione of the ester 33.
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Y. Kamano, M. Inoue, G. R. Pettit, M. Tozawa
Article type: Article
Session ID: 19
Published: September 10, 1980
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Epoxidation reactions of bufadienolides with hydrogen peroxide and tris (acetyl acetonate) Iron (III) were studied, since the peracids such as m-chloroperbenzoic acid do not attack the 2-pyrone ring double bonds but hydrogen peroxide-tris (acetyl acetonate) Iron (III) was found to give a 20,21ξ-epoxyderivative. With 14-dehydrobufalin (1), the reaction gave 2-pyrone epoxide 3 as an intermediate that was transformed into 14,15α;20,21ξ-diepoxide 4. The diepoxide (4) was also obtained in the same manner from 14,-15α-epoxybufalin(2). Epoxidation of the 2-pyrone ring system was more smooth than that of steroidal 14-olefin. The similar reaction provided the bufadienolide 2-pyrone epoxides, 6, 8, 13 and 14, respectively. Although bufalin (9) gave 20,21-epoxide 10 by the same method, 2-pyrone epoxide 10 was found to isomerize slowly with contact on silica gel to give cyclic ethers, 11 and 12. The isomerization reaction suggests that the 14β-hydroxy group is located near the 21- and 22-carbon position. As another reaction, epoxidation of the 14,21-epoxy-20(21),22-dienoate(15) provided the two compounds, 16 and 17, respectively.
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M. Suzuki, S. Sugiura, T. Kawagishi, T. Suzuki, R. Noyori
Article type: Article
Session ID: 20
Published: September 10, 1980
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Newly developed tools for prostaglandin synthesis are described. (1) Transition metal catalyzed reactions of strained oxygen ring systems provide useful methods for site-specific oxygenation of unsaturated carbon skeletons. The reaction pathway of the palladium(0) catalyzed reaction of 1,3-diene 1,2-epoxides is highly dependent on the structure and substitution pattern of the substrates; epoxides derived from flexible dienes isomerize to dienol isomers, whereas cyclic diene epoxides are transformed to β,γ-unsaturated ketones selectively. 1,3-Diene 1,4-epiperoxides give 4-hydroxy-2-alkenones or syn diepoxides depending on the nature of the catalysts. (2) New procedures for vicinal carbon group introduction to α,β-unsaturated ketones have been elaborated on the basis of stoichiometric use of organocopper reagents. Utility of such methodologies is illustrated by the straightforward synthesis of certain prostaglandin derivatives.
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A. Tanaka, K. Yamashita
Article type: Article
Session ID: 21
Published: September 10, 1980
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The total synthesis of (-)-dihydromahubanolide B (1a) and (-)-isodihydromahubanolide B (1b), two components of the amazonian Lauraceae, Licaria mahuba (Samp.) Kosterm. has been accomplished starting from natural L-(+)-tartaric acid. Synthetic efforts directed toward the synthesis of obtusilactone A (2a) and iso-obtusilactone A (2b), structurally related compounds isolated from the Japanese Lauraceae, Lindera obtusiloba Blume. have been also described. Thus, natural L-(+)-tartaric acid was converted to the known hydroxy ester 3 which gave in several steps the keto benzoate 6, a key intermediate of the route. Keto benzoate 6 was transformed into (-)-dihydromahubanolide B (1a) and (-)-isodihydro-mahubanolide B (1b) by the reaction sequence involving the Wittig reaction, oxidation and acid treatment. The hydroxy ester 3 afforded the lactones 4a and 4b according to the sequence similar to that described above. Conversion of these lactones into 2a and 2b is now under investigation.
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Kanzo Sakata, Rodney W. Rickards
Article type: Article
Session ID: 22
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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The fungus Trichoderma koningii Oud. agg. produces volatile metabolites which stimulate sexual reproduction in one of the two mating types of phytopathogenic fungus Phytophthora cinnamomi Rands. The compounds responsible for this phenomenon have been identified as the novel isocyanides, homothallins I (1) and II (2). A model compound (3) was synthesized from 5 by formylation followed by dehydration with phosgene/triethylamine to examine the chemical properties of the vinylogous acyl-isocyano group. The product is very unstable and easily polymerizes, clarifying the extreme instability of 2. Homothallin II (2) was synthesized from 1,2,4-cyclopentantrione in six steps. Selective hydrolysis of 8 was not successful, but the amino compound (11) gave an enaminoketone (13) in a good yield. Vinylation of 13 gave 15 in a very low yield. An alternative synthesis of 15 was achieved as follows. Alkylation of 4 with acetaldehyde followed by dehydration yielded 19 as a main product. Compound 19 was not oxidized with H_2O_2 but with m-chloroperbenzoic acid to the epoxide (21). Opening of the epoxide with a selenolate anion gave a selenide (22) as well as a considerable amount of a diastereoisomeric mixture of 16. Amination followed by formylation gave 24. Oxidative elimination reaction of 24 followed by dehydration by the phosgene method yielded, though in a very low yield because of polimerization, (±)-homothallin II (2).
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Shinji Fushiya, Yoshikazu Sato, Shuichi Nakatsuyama, Shigeo Nozoe
Article type: Article
Session ID: 23
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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Several amino acid derivatives possessing an iron chelating activity have been isolated from the excreta of root of oats cultured under iron deficient conditions. During the course of studies to isolate such amino acid derivatives, avenic acid B 1 was isolated from an ethanol extract from the root of Avena sativa. The structure of this compound was confirmed as 2(S),3'(S)-N-(3-hydroxy-3-carboxypropyl)-homoserine on the basis of nmr analysis and by chemical synthesis. Synthesis of 1 was achieved through reductive coupling of L-malic half-aldehyde derivative 17 to L-homoserine lactone hydrobromide 18 by using of NaBH_3CN, a selective reducing agent, followed by hydrolysis. Avenic acid A, 2(S),3'(S),3"(S)-N-[3-(3-hydroxy-3-carboxypropylamino)-3-carboxypropyl]-homoserine 2, a chelating amino acid isolated from the root washings of Avena sativa was also synthesized in the same way. Reaction of homoserine lactone hydrobromide 18 with L-aspartic-β-semialdehyde 9c gave 20c. Reductive coupling of 22, the decarbobenzoxylation product of 20c and L-malic half-aldehyde derivative 17 yielded avenic acid A after deprotection. Nicotianamine, 2(S),3'(S),3"(S)-N-[N-(3-amino-3-carboxypropyl)-3-amino-3-carboxypropyl]-azetidine-2-carboxylic acid 3, an amino acid derivative being widely distributed in Solanumplants and 2(S),3'(S)-N-(3-amino-3-carboxypropyl)-azetidine-2-carboxylic acid 4, isolated from Fagus silvatica L. were also synthesized from L-azetidine-2-carboxylic acid 24 and L-aspartic-β-semialdehyde derivatives (9a, 9c).
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A. Dobashi, K. Oka, S. Hara
Article type: Article
Session ID: 24
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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The optical resolution of amino acid derivatives by the normal phase HPLC was performed using chemically bonded chiral silica and binary solvent systems. It is our aim to inquire the driving force based on hydrogen bonding association between the stationary surface and solutes concerning with the resolution of the enantiomers. Five grafted silicas were obtained by bonding of N-acyl-L-valines Me_2CHCH(COOH)NHCOR (R=H, Me, Et, n-Pr, n-Bu) onto 3-aminopropylsilanized (APS) silica. The most effective separation was obtained by the column which contains N-formyl-L-valylaminopropylsilanized (FVA) silica. Derivatization of amino acids was carried out by the acylation of amino group and esterification of carboxyl group. Effects of bulkiness of the alkyl moieties on each functional group on the chromatographic separation were examined carefully using several binary solvents consisted of n-hexane as the nonpolar component and 2-propanol, diethyl ether, dichloromethane, or chloroform as the stronger component. Highest values of the separation factor a were obtained with N-acetyl-O-t-butyl derivatives of seventeen pairs of enantiomers of natural and synthetic amino acid family and aprotic solvent systems. The peak tailing was minimized with protic solvent system such as n-hexane and 2-propanol mixture affording base-line separations. Enantiomers and diastereomers of di- and tripeptides containing benzyloxycarbonyl substituent as protecting group were also resolved by the FVA-column so that the method will be applied to the peptide synthesis with high optical purities of target molecules.
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Masakatsu Shibasaki, Katsuhiko Iseki, Shiro Ikegami
Article type: Article
Session ID: 25
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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A total synthesis of (±)-coriolin, an antibacterial and antitumor sesquiterpenoid, has been accomplished starting from 1,3-cyclooctadiene. (1) Synthesis of the enone (1), a versatile intermediate The enone (1) was successfully contructed from the simple alcohol (2) by two routes. One of the routes involving regio and stereo-controlled bromohydrin formation (7) was found to be applicable to practical scale synthesis of 1. (2) Introduction of functional groups to the enone (1) A conjugate addition of dimethylcopperlithium to the enone (1) afforded the methyl ketone (11) in high yield, which was followed by regiospecific alkylation and reduction of a carbonyl group to provide the alcohol (13) efficiently. (3) Synthesis of (±)-coriolin The alcohol (13) was converted to (±)-coriolin in 13 steps. Introduction of an acetonyl group (18) and a hydroxy group (27) in the regio and stereocontrolled manner is a characteristic point. The present total synthesis would be easily applicable to synthesis of various coriolin analogs. (4) Synthesis of the prostacyclin analog (29) In order to point out versatility of the key intermediate (1), application to synthesis of the prostacyclin analog (29) is briefly presented. Application of the present synthesis to asymmetric synthesis including asymmetric epoxidation of 1,3-cyclooctadiene is currently under investigation.
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G. Stork, E. Nakamura
Article type: Article
Session ID: 26
Published: September 10, 1980
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Two approaches directed toward the synthesis of the macrocyclic moiety of the title compounds, i.e. internal Emmons-Horner and internal Diels-Alder reaction, have been studied. An internal Diels Alder reaction of 24, derived from the trienic ester 23 and the ketolactam 12, followed by a regio- and stereoselective epoxidation reaction provided cycochlasin F. Conversion of cytochalasin F to cytochalasin A and B has been effected by a highly regioselective epoxide rearrangement.
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Y. Sato, T. Oda, H. Saito
Article type: Article
Session ID: 27
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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The microbial transformation of (-)-dehydrogriseofulvin (1a) to (+)-griseofulvin (2a) was initially investigated by Andres et al. using Streptomyces cinereocrocatus NRRL 3443. Since then, by means of ^2H NMR we showed the stereo-chemical course of the microbial hydrogenation of natural (-)-[5'-^2H]dehydrogriseofulvin (1b) into natural (+)-[5'α-^2H]griseofulvin (2b) by the same microorganism. We now proved that in the microbial transformation by S. cinereocrocatus (+)-[5'-^2H]dehydrogriseofulvin (3b) is transformed to (+)-[5'α-^2H]griseofulvin (2d). Further, (-)- and (+)-dehydrogriseofulvin (1a and 3a) were subjected to the microbial transformation by seven Streptomyces species (S. roseocromogenus, S. bikiniensis, S. griseinus, S. durhamensis, S. californicus, S. fimbriatus, and S. cinereoruber), respectively, as in the case of S. cinereocrocatus and it was found that the recovered dehydrogriseofulvin is a mixture of (-)- and (+)-enantiomer as a result of isomerization and the product, griseofulvin, is mainly compose of (+)-enantiomer, except for (-)-enantiomer in the case of the fermentation of (+)-dehydrogriseofulvin by S. cinereoruber. Our results also showed that the microbial systems are effective to produce natural (+)-griseofulvin from racemic (±)-dehydrogriseofulvin, which would be a candidate as intermediates in a practical synthesis.
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Akitami Ichihara, Hideaki Oikawa, Kazuo Murakami, Makoto Ubukata, Sada ...
Article type: Article
Session ID: 28
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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Eleutherins (2a,2b), caryopteron (3) and dideoxycryptosporin (22) have been synthesized by regiospecific manner. I) Synthesis of eleutherins (2a,2b). The starting material (5) derived from a Diels-Alder adduct was treated with CH_3MgI to give the hemiacetal 6, which was converted to the diol 8 by the Wittig reaction. Oxidation of 8 with manganese dioxide, and oxymercuration yielded 10. DDQ oxidation of 10 and methylation afforded eleutherin (2a) and isoeleutherin (2b). II) Synthesis of caryopteron (3). The Diels-Alder adduct 13 derived from 1 and dihydroanisol was alkylated with prenyl bromide to give 14a.The retro-Diels-Alder reaction, and epoxidation with NaBO_3 afforded 16a, which was converted to dihydrocaryopteron 17c with BF_3-DDQ. By acetylation, bromination and dehydrobromination, 17c was converted to 3. III) Synthesis of cryptosporin (4). The Diels-Alder adduct 19 was alkylated with crotyl bromide to give 20a, which was transformed to 21 by the retro-diene reaction and epoxidation with NaBO_3. Acid treatment of 21 yielded dideoxycryptosporin 22. Conversion of 22 to 4 is in progress.
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Fatima Z. Basha, Satoshi Hibino, Deukjoon Kim, Walter E. Pye, Tei-Teh ...
Article type: Article
Session ID: 29
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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Streptonigrin (1), an antitumor antibiotic natural product isolated from a few species of Streptmyces, was shown by chemical studies, CMR and X-ray analysis to have sturucture (1). We report here the first total synthesis of streptonigrin. Epoxydation of aldehyde (4), followed by Grignard reaction with vinylmagnesium bromide gave alcohol (6). Oxidation of (6) yielded the α,β-unsaturated aldehyde (7), which was converted to diene (8). Diels-Alder reaction of (8) with methoxyhydantoin (9) gave the desired adduct (10) along with regioisomer (11). Hydrolysis of adducts (10) and (11), followed by esterification afforded (13), and then aromatization of (13) gave the desired pyridine (14). Rearrangement of N-oxide (15) with acetic anhydride afforded acetate (16), followed by hydrolysis and chlorination gave chloride (18), which was alkylated with N-cyanomethylpyrrolidine to form quaternary salt (19). Treatment of (19) with t-BuOK and then oxalic acid yielded aldehyde (20). Oxidation of (20) with PTFA gave N-oxide (21) which was further oxidized to carboxylic acid (22). Curtius rearrangement of (22) afforded amine (23) which was converted to aldehyde (26) with three steps. This aldehyde (26) was led to hydroxyphosphonate (27) and oxidation of (27) provided ketophosphonate (28). Condensation of (28) with nitroaldehyde (29) gave nitrochalchone (30). Reductive cyclization of (30) gave the tetracyclic compound (31) and removal of sulfonate of (31) yielded the A-ring phenol (32). Fremy's salt oxidation of (32) produced quinone (33), which was converted to the aminoquinone (34). Debenzylation of (34), followed by hydrolysis of the ester group of (35) afforded synthetic streptonigrin (1) indistinguishable from the natural product.
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Shiro Terashima, Norihiko Tanno, Sang-sup Jew, Kenji Koga
Article type: Article
Session ID: 30
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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Preparation of optically active anthracyclinones(2), the aglycones of anthracycline antibiotics(1) showing promising anticancer activities, was attempted by employing two different types of asymmetric syntheses. Thus, the asymmetric bromolactonization of (S)-N-(α,β-unsaturated) acylprolines ((S)-13) was found to give the bromolactones(14) in which one diastereomer(14A) was highly predominant. Further chemical elaborations of 14 including debromination and hydrolytic cleavage of the (S)-proline moiety afforded (R)-α-hydroxy acids((R)-16). (R)-16a,b were converted to (R)-α-hydroxy ketone((R)-9a), 92%ee, a model compound of the AB ring system of 2, and (R)-9b, 100%ee, one of the most versatile synthetic intermediates for 2, respectively. On the other hand, the chiral hydride prepared by partially decomposing lithium aluminum hydride with (-)-N-methylephedrine(1eq) and N-ethylaniline(2eq) was found to reduce the methyl ketone (24) highly stereoselectively, giving (S)-allyl alcohol((S)-25), 92%ee, in a quantitative yield. Optically pure (S)-25 obtained in 87% yield based on 24 by recrystallization, was elaborated to (R)-9b, 100%ee, by successive epoxidation, reduction, and oxidation. (R)-α-Hydroxy ketone((R)-9b) was further transformed to (R)-9c, the synthetic intermediate of 2e, the aglycone of 1e having improved therapeutic properties. Based on the above studies, it became possible to prepare various types of 2 by asymmetric synthesis.
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K. Tatsuta, Y. Amemiya, S. Maniwa, M. Kinoshita
Article type: Article
Session ID: 31
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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Medicinally important 16-membered-ring macrolide antibiotics, carbomycin B (1) and josamycin (2, leucomycin A_3), have been stereospecifically synthesized by using D-glucose as a major chiral source. The Michael reaction of the unsaturated ester, which was derived from the furanose 4 by the Wittig reaction, with the lithiated methyl methylthiomethyl sulfoxide gave stereospecifically the adduct 7, which, in turn, was converted into the aldehyde 10. The second Wittig reaction with the ylid 11 followed by reduction afforded a C1-C10 segment. Selective oxidation of the primary alcohol followed by esterification provided the methyl ester 13, which was coupled with an aldehyde segment 15 corresponding to C11-C16 to give the naturally derived unsaturated ketone 16. Alkaline hydrolysis followed by lactonization gave the 16-membered lactone 20, which was converted into the ethylene acetal aglycone 24. Since the key aglycone 24 has already been transformed into carbomycin B (1) and josamycin (2, leucomycin A_3), the total synthesis of 24 constitutes the completion of the task.
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Tadashi Nakata, Takeshi Oishi
Article type: Article
Session ID: 32
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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Erythromycin A (1), produced by the fungus Streptomyces erythreus, is one of the most important compounds among macrolide antibiotics. We now report our recent studies toward the total synthesis of erythronolide A (2), the aglycone of erythromycin A. Stereoselective synthesis of erythro-3-hydroxy-2-alkylpropionates Erythro-3-hydroxy-2-alkylpropionates 13, an important fragment for the synthesis of macrolide antibiotics, were prepared in high stereoselectivity and in high isolated yield by zinc borohydride reduction of the corresponding β-keto esters 10. Stereoselective synthesis of C_8-C_<15> and C_3-C_7 fragments Epoxidation of erythro-hydroxy ester 13e with t-BuOOH-VO(acac)_2 gave the erythro-epoxide 26 exclusively. Subsequent hydrogenation afforded the lactone 28. The ketone 15 corresponding to C_8-C_<15> fragment of erythronolide A (2) was successfully synthesized from the lactone 28, by eight steps: 1) Me_2C(OMe)_2/p-TsOH, 2) LiAlH_4, 3) Ac_2O/Py., 4) DMSO/Ac_2O, 5) K_2CO_3/MeOH, 6) PCC, 7) EtMgBr, 8) PCC. The aldehyde 38 corresponding to C_3-C_7 fragment of 2 was also prepared from β-keto ester 10f in high stereoselectivity.
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S. Masamune, S. Mori, M. Hirama, D. Garvey
Article type: Article
Session ID: 33
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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A stereoselective, directed aldol condensation to construct erythro (2,3-syn)-and threo (2,3-anti)-β-hydroxy-α-methyl carbonyl systems has been achieved via Z- or E- boron enolate. E-enolate of 12 and Z-enolate of 13 generated stereoselectively by a combination of 14 and diisopropylethylamine reacted with aldehydes to afford erythro aldols exclusively. On the other hand, Z-enolate of 15 and E-enolate of 13 prepared by 16 and the same amine gave rise to threo-aldols selectively. Thus, a 2,3-stereochemical problem has been solved, while the complete control of 3,4-stereochemistry regarding Cram rule has not been realized yet. This new methodology was applied to a synthesis of 6-deoxyerythronolide B (2). The four aldol condensations using boron enolates constituted crucial C-C bond forming steps, including simplified synthesis of Prelog-Djerassi lactone (28). The Cu(I)-mediated thiol ester activation brought about lactone ring formation, which completed the synthesis of 2. The total number of steps used to create 10 chiral centers is impressively small as compared with those required in recent syntheses of macrolides of a similar type and complexity.
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Y. Umezawa, S. Saito, H. Morishima, T. Takita, H. Umezawa, S. Kobayash ...
Article type: Article
Session ID: 34
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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Bleomycin (BLM) is an antitumor antibiotic clinically used in the chemotherapy of squamous cell carcinomas and malignant lymphomas. BLM is a glycopeptide and contains many unusual amino acids in its molecule. Recently unique mode of action of BLM has been revealed. For the strategy of the synthesis of BLM, we segmented the aglycon of BLM into three fragments: pyrimidoblamic acid [A], polyfunctional dipeptide [B] and tripeptide S [C]. The key intermediates to synthesize pyrimidoblamic acid are 3-amino-2-t-butoxycarbonyl-aminopropionamide (Boc-DAPA 1) and ethyl 6-chloro-2-formyl-5-methylpyrimidine-4-carboxylate (2). 1 was prepared from Boc-L-asparagine by Hoffmann degradation, protection by benzyloxycarbonyl group, esterification with diazomethane, treatment with ammonia and removal of the benzyloxycarbonyl group by catalytic hydrogenation. 2 was prepared from ethyl α-ethoxalylpropionate and diethoxyacetamidine followed by treatment with POCl_3. The side chain at the C-2 of the pyrimidine ring of [A] was formed by a C-2 unit addition to the Schiff base prepared from (1) and (2) by 1) malonic acid half ester or 2) vinyloxyborane method. Boc^α or Z^α-DNP^<im>-hydroxyhistidine and 4-amino-3-hydroxy-2-methylpentanoic acid methyl ester were coupled with EEDQ to give [B]. Tripeptide S [C] was prepared by DCC and active ester methods without any trouble. We are now preparing the aglycon of BLM from fragments of [A], [B] and [C].
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M. Aratani, M. Hashimoto
Article type: Article
Session ID: 35
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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A synthetic method for the 3-azacephem and 3-azacepham nuclei 15, 17, and 18,structurally novel analogues of cephalosporin (II), has been established starting from penicillin V. The azide 6 was prepared from the thiazoline 1. More conveniently, 6 was constructed from the 4-mercaptoazetidine 7 via the oxamide 10. Reduction, formylation, and dehydration then yielded the 4-mercaptoisonitrile 16, a key intermediate of the synthesis. Removal of the protecting group in 16 resulted in the direct formation of the Δ^2-3-azacephem 15 via a spontaneous cyclization of the intermediate thiol. The isomerization of the Δ^2 double bond in 15 to the Δ^3-position could be achieved in a regiospecific manner. Thus, reduction of 15 to the 3-azacepham 18, followed by conversion into the triflamide 19 and treatment with DBU, afforded the Δ^3-3-azacephem 17. The β-lactam system of this new cephem nucleus 17 was found to be highly reactive, while its Δ^2-isomer 15 is relatively stable. Some of the new cephem and cepham derivatives showed an antimicrobial activity.
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Miwako Mori, Katsumi Chiba, Minoru Ishikura, Toshihito Ikeda, Yoshio B ...
Article type: Article
Session ID: 36
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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A new facile synthetic method of heterocyclic compounds using palladium catalyzed carbonylation to an aryl or vinyl halide which was developed by us has been extended to the syntheses of the natural compounds. Sendaverine, which was isolated by Manske and possesses a tetrahydroisoquinoline skeltone was synthesized by the insertion of carbon monoxide to 2-bromophenethylamine derivative (10). It was found that the diazepine derivatives were easily prepared from o-bromoaniline and amino acid by use of this carbonylation. Thus, the compound(24) was synthesized from o-bromoaniline and proline. And moreover, the key intermediate(38) of the synthesis of the antibiotics, tomaymycin(19) and SEN-215(20) was also synthesized from 2-bromo-4-methoxy-5-tosyloxy aniline(32) and L-hydroxy proline(33). For the application of the new synthesis of α-methylene-β-lactams, (±)-3-aminonocardicinic acid which is an important starting material for the synthesis of nocardicin A(42) and other biologically active analogues, has been synthesized. Palladium catalyzed carbonylation to the amine(48) which was prepared fron DL-p-hydroxyphenyl glycine (44) was smoothly proceeded under 4 atm pressure of carbon monoxide to afford the desired α-methylene-β-lactam(49b) in a good yield. α-Methylene group was converted to 3-amino group through four stages. The hydrotosylate(54b TsOH)of one isomer of the diastereomers was fully identical to an authentic sample kindly provided by Professor Wasserman.
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Minoru Isobe, Masato Kitamura, Yoshiyasu Ichikawa, Toshio Goto
Article type: Article
Session ID: 37
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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We have recently developed the heteroconjugate addition and acyclic asymmetric induction aiming at total synthesis of maytansine [1]. Here we describe novel stereocontrolled elaboration of carbon-carbon bonds and functional groups of this molecule. Methyllithium was designed to add to such hetero-olefins as 2 that have substituents with alpher asymmetric center with which the lithium cation can coordinate by chelation so as the methyl anion to add pseudo-intramolecularly. The free hydroxyl cases (in Table 1) showed the best asymmetric induction exceeding 99% threo isomer. Pyranosyl hetero-olefin [12] was prepared from acrolein dimer as racemic-sugar model to look at the asymmetric induction. In cases of the methoxyethyl pyranosides, the addition of methyllithium also underwent perfectly. D-Mannose was converted into the optically active synthetic intermediate (Fig. 8, 9) which corresponds to carbon five through carbon eleven of 1. Further synthetic studies toward 1 will be discussed.
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S. Kusumoto, M. Inage, H. Chaki, T. Shiba
Article type: Article
Session ID: 38
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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Liposaccharide component called "Lipid A" is a common structural unit of bacterial endotoxin, possessing most of the biological activities of endotoxin, e.g., lethal toxicity, pyrogenecity, adjuvant activity, antitumor effect and so on. Though the basic sturucture of lipid A has been recently established as 1, it exists in natural state as a mixture of congeners and analogs in fatty acid moieties and has never been obtained as a chemically pure substance. Therefore, synthetic approach to this lyposaccharide has been keenly requested particularly for the purpose of elucidation of the relationship between chemical structure and biological activity. We now describe the preparation of two acylated gulcosamine disaccharides 2 and 3 corresponding to the fundamental sturucture of Salmonella-type lipid A lacking phosphate moiety. While tetradecanoic acid was used for N- and O-acylations in 2, synthetic optically pure (R)-3-hydroxytetra-decanoic acid was employed for N-acylation in 3. Test of these synthetic liposaccharides for various biological activities of lipid A is now in progress.
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H. Ogura, K. Furuhata, Y. Shitori, M. Itoh
Article type: Article
Session ID: 39
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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The N-acetylneuraminic acid (NANA) having the widest biological disribution related sialic acid is α-glycoside linkage to glycoprotein and glycolipid of neuronal and other cell menbranes. We obtaned appreciable amounts of NANA that can be isolated under mild aqueous hydrolytic conditions from edible birds'nest in high yield and without contamination of another acylneuraminic acid by utilizing a modified procedure of Czarniecki and Thornton. CD spectra of NANA and its derivatives show two bands. The main band, centered below 200nm, is attributed to the acetamido groug. Weak band between 225-240nm arise from the n-π^*trasition of the carboxy chromophore, α-glycosides of NANA show a negative band, while β-glycosides give to a positive band. The conformation of NANA and its derivatives were established from the observed Cotton effect of the carboxy chromophore by application of the planar rule. NANA derivatives were prepared by the condensation of 2-chloro-4,7,8,9-penta-O-acetylneuraminic acid methyl ester (9) with 2,3-isopropylidene-D-ribonolactone, 1,2,3,4,-tetra-O-acetyl-β-D-glucopyranose, 2',3'-isopropylideneuridine, 5-fluoro-2',3'-isopropylidine, and Z-serine metyl ester respectively, according to the Koning-Korr technique.
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T. Ogawa, K. Sasajima, K. Katano, M. Matsui
Article type: Article
Session ID: 40
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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Regioselective transformation of carbohydrates through trialkylstannylation of hydroxyl groups and the application of the procedure to the synthesis of cell surface glycan chains are described. For example, tributylstannylation of 30 and subsequent benzoylation with benzoyl chloride gave dibenzoate 32 in 90% yield via 31 as the activated intermediate. Similar regioselective benzoylation of mono- and di-saccharides are achieved in high yields, giving partially benzoylated carbohydrates of synthetic importance such as 15, 22, 35, 38, 40, 42, and 44. Similar regioselective alkylation of the partially stannylated monosaccharides was achieved. For example, 31 was heated in allylbromide to afford diallyl ether 45 in 71% yield. 45 was further transformed into dibenzyl ether 47 of which structure was confirmed by the transformation into dibenzoate 32. Compound 47 could be regarded as the key intermediate for the synthesis of cell surface glycans such as 49 and 50. In fact, 47 was successfully employed for the synthesis of model glycans 51, 52 and 53. Key monosaccharide synthons for these branching mannopentaosides and mannohexaoside are 47, 54 and 55. The glycosyl donors 54 and 55 could readily be prepared from 56 and 57. The reaction of 54 and 47 gave a 78% yield of 58. Deacetylation and subsequent glycosidation of 59 with 54 led to the isolation of 60 in 79% yield which was deprotected to give free mannopentaoside 51. In a similar manner, branching mannopentaoside 52 and hexaoside 53 were synthesized from the same synthons, demonstrating the efficiency of our approach to the synthesis of branching glycan chains.
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T. Kametani, M. Ihara, T. Ohsawa, N. Kanaya, K. Fukumoto
Article type: Article
Session ID: 41
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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Utilizing the reaction of singlet oxygen with enamine systems, an approach to the synthesis of mitomycins and total syntheses of brevianamide E and camptothecins were carried out. (1) An Approach to the Synthesis of Mitomycins: 7-Methoxy-6-methyl-9-oxo-9H-pyrrolo[1,2-a]indole (6) was prepared from 2-(2'-bromo-5'-methoxy-4'-methylbenzoyl)pyrrole with sodium hydride and cuprous bromide. Photo-oxygenation of 6 in methanol in the presence of Rose Bengal yielded the hydroperoxide (9) and the hydroxide (10). (2) The Chiral and Stereoselective Total Synthesis of Brevianamide E: Condensation of 3-dimethylaminomethyl-2-(1',1'-dimethylallyl)indole and (-)-3-methoxycarbonyl-1,3,4,7,8,9-hexahydro-6H-pyrrolo[1,2-a]pyrazine-1,4-dione (16) (derived from L-proline) followed by demethoxycarbonylation gave (-)-deoxybrevianamide E (13) and its epimer (18). Photo-oxygenation of 13 and 18 produced (-)-brevianamide E (19) and its three stereoisomers (20, 21 and 22). The absolute stereochemistry of brevianamide E (19) was determined to be 4aS, 5aR, 10aS, 11aS as a result of this chiral synthesis. (3) Total Synthesis of (±)-Camptothecin and (±)-10-Methoxy-camptothecin: Condensation of 3,4-dihydro-1-methyl-β-carbolines (29 and 30) with a mixture of the tetra-esters (33), followed by reduction and concurrent cyclization (enamine annelation), produced indolo[a]-quinolizin-4-ones (36 and 37). Photo-oxygenation of 36 and 37, followed by recyclization, gave indolizino[1,2-b]quinolones (40 and 41) which were transformed into (±)-camptothecin (26) and (±)-10-methoxycamptothecin (28) according to a modification of Winterfeldt's method.
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H. Muratake, M. Natsume
Article type: Article
Session ID: 42
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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6,7-Secoagroclavine (3), an ergot alkaloid isolated from Claviceps purpurea, strain AA-218, was first synthesized from 1-methoxycarbonylpyrrole (1). Endoperoxide (4) of 1 was reacted with 1-trimethylsilyloxy-1,3-butadiene in the presence of SnCl_2 and 4-(1-methoxycarbonyl-2-pyrrolyl) crotonaldehyde (6) thus obtained was treated with the Grignard reagent derived from 2-methyl-2-bromoethyl-1,3-dioxolane, followed by oxidation with pyridinium chlorochromate to produce 7. SnCl_4 catalyzed cyclization of 7 afforded 1-methoxycarbonyl-4-(3-oxo-1-butyl) indole (2) in 52% yield, accompanied by concomitant hydrolysis of the dioxolane group. 2 was transformed to 21 by way of 19 and 20, and the formylation of 21 with the Vilsmeier-Haack reagent, followed by alkali treatment produced a tricyclic indole derivative 22, which was reduced with LiAlH_4 in THF. Successive treatment of the reduction mixture with i) ClCOOMe, Et_3N in CH_2Cl_2, ii) LiAlH_4 in THF, and iii) ClCOOCH_2Ph, Et_3N in CH_2Cl_2, afforded 23d and 24d in 27% and 33% yields, respectively. After removal of the ethylene ketal group from 23d, 25d=35 was treated with MeMgI, followed by dehydration with p-TsOH in boiling benzene gave 40, whose protecting group on the nitrogen was cleaved with Na in liquid NH_3 to complete the total synthesis of ±-3.
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Seiichi Takano, Susumi Hatakeyama, Mikoto Takahashi, Masahiro Yonaga, ...
Article type: Article
Session ID: 43
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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Stereoselective synthesis of some indole alkaloids has been accomplished. 1) Starting from (±)-norcamphor(1), an alternative synthesis of (±)-corynantheidol(26) and the first synthesis of (±)-antirhine(41) have been accomplished via the dithiane intermediates, (18) and (31), respectively. Using the same methodology, a synthesis of (±)-corynantheine(37) has been also attempted. 2) Starting from a symmetric carboxylic acid(51), a new synthetic route to the aspidosperma type alkaloids, e.g., (±)-quebrachamine(48), and the vincamine-eburnamine type alkaloids, e.g., (±)-eburnamine(46), has been developed using halolactonization reaction as a key reaction. Since the chiral halolactone(52) in both enantiomeric forms has been also obtained using (S)-proline as a chiral template, the present synthesis would imply a chiral synthesis. 3) In relating to the synthesis using a halolactonization reaction, the key intermediate(54) has been prepared in a chiral form using the chiral lactone(63), prepared from (S)-proline(62) by Yamada's method. The chiral lactone(54) obtained has been then converted into (+)-quebrachamine(48) in highly enantioselective manner under the same conditions as the racemate. Employing the same methodology, the chiral lactone(63) has been also transformed into the iboga type alkaloids, (-)-velbanamine(74) and (+)-isovelbanamine(75) through the 2-ethylallyllactone(67).
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T. Imanishi, H. Shin, N. Yagi, M. Hanaoka
Article type: Article
Session ID: 44
Published: September 10, 1980
Released on J-STAGE: August 18, 2017
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Formal syntheses of (±)-catharanthine, one of the Iboga alkaloids, and (±)-tabersonine, one of the Aspidosperma alkaloids, were achieved from N-ethoxycarbonyl-1,6-dihydro-3(2H)-pyridinone (1a) as a common starting material. The key intermediate (7) for the Iboga alkaloids was prepared by two routes. The first route involved haloform reaction of 12, obtained from 2. The second one consisted of the Claisen rearrangement of 17, the precursor of 1a, and the subsequent hydroboration-oxidation. Ketalization of 7c and the subsequent PCC oxidation gave 42, which was converted to 50 via 49. Cyclization of 50 with p-TsOH afforded the pentacyclic ketone (51), which had already been transformed into (±)-catharanthine. On the other hand, 1a was treated with ethylmagnesium bromide to give the 1,2-adduct (54) along with the 1,4-adduct (55). Allylic rearrangement of the former, followed by the Claisen rearrangement, afforded 57, which was acetalized, hydrolyzed, and condensed with β-indolylacetyl chloride to give 60. The aldehyde (60) was smoothly oxidized with Ag_2O to yield 61, which then cyclized with PPA to (±)-5,16-dioxo-14,15-dehydroquebrachamine (53), the key intermediate for (±)-tabersonine. Thus, 1,6-dihydro-3(2H)-pyridinone system has been proved to be a potential synthon to some indole alkaloids.
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