From the medicinal plants Gelsemium, various skeletal type of indole alkaloids were isolated. Along the biogenetic speculation of these alkaloids, some of the structurally complex compounds, involving sarpagine-, humantenine-, koumine-, and gelsedine-type, were prepared from ajmaline and the Gardneria alkaloids. In the second half of this article, recent synthetic studies on the sarpagine type alkaloids and on a principal Gelsemium alkaloid, gelsemine, are reviewed.

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We have recently investigated the alkaloidal constituents of Gelsemium elegans, a toxic medicinal plant from Thailand and proposed the biogenetic route of these alkaloids having novel polycyclic systems. In order to support the biogenetic speculation and to develop the efficient synthetic method of these alkaloids including the minor constituents, we designed the biomimetic partial synthesis of some gelsemium alkaloids from easily obtainable compounds. Koumidine (4) is a plausible biogenetic precursor of the new alkaloid, 19-(Z)-taberpsychine (5) and its structure was revised. Both to provide support for the spectroscopic analysis and to determine the absolute configuration of these compounds, we have synthesized them from ajmaline (16). Koumidine (4) was also prepared from gardnerine (22) by the demethoxylation from indole nucleus and the inverting the configuration of the ethylidene side chain with palladium catalyst. Along the biogenetic speculation, a principal gelsemium alkaloid, koumine (6) was synthesized from 18-hydroxygardnutine (28) by the demethoxylation from indole ring and palladium-catalyzed cyclization between C_7 and C_<20> of biogenetic intermediate (27). A synthetic intermediate (45), which was corresponding to the biogenetic intermediate (12) for gelsedine (13), was prepared from ajmaline (16) in 21 steps via the deformylation (C_<21>) and the construction of five-membered D-ring having an α-ethyl group on C_<20>. Talcarpine (49), one of the macroline-type pleiocarpa alkaloid, was synthesized from (16) in 10 steps and the configuration at C_<19> was determined to be (R) by the analysis of 2D-NMR spectra.

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Up to now, more than two thousands indole alkaloids having structural variety have been found from the three families of Gentianales : Loganiaceae, Apocynaceae, and Rubiaceae plants. These compounds generally possess characteristic biological activities and many of them are utilized for the medicinal purpose and for the lead-compounds to develop new synthetic drugs. The author of this review has been investigated the alkaloidal constituents of the above mentioned plants native to Japan and overseas countries. Especially, a cooperative work with Thai researchers concerning the plants in Thailand was developed. On the basis of biogenetic consideration of the structures of monoterpenoid indole alkaloids, chemical bond cleavage between the C3-N4 linkage in the C/D ring of indole alkaloids was discovered. It was speculated that, either in biogenesis, the flexibility of the ring-opening compounds having ten membered ring enabled the construction of indole alkaloids having highly strained polycyclic structures. Along with this conception, the syntheses of structurally complex indole alkaloids utilizing a biomimetic procedure have been investigated. In this review, recent results on the chemical synthesis of many skeletally varied Gelsemium alkaloids (Loganiaceae plant) are mainly described.

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To discover new antitumor natural products, we carried out investigation of the alkdloids in Gelsemium elegans and G. rankinii (Loganiaceae), resulting in teh isolation and structure elucidation of twenty one new alkaloids. Ten new gelsedine-type alkaloids (1-10) were isolated from G. elegans. Gelsevanillidine (1) is the first example of a monoterpenoid indole alkaloid having a vanillin residue on the side chain. Gelsoeoxazolidinine (7) consists of a hexacyclic skelton with an unprecedented oxazoliding ring. To confirm their unique structures, the chemical transformation of a known humantenine-type alkaloid 7 was performed. Ten new humantenine-type alkaloids were isolated from G. elegans and G. rankinii. Rankiniridine (24) and humantenrirdine (21) are new type of alkaloids having a nitrogen-carbon linkage between a humantenine-type monoterpenoid indole alkaloid and a monoterpene unit having an iridoid skeleton. 6-Hydroxyhumantenine (25) is the first example of a Gelsemium alkaloid with an oxygen function at C-6 position. From a biogenetic point of view, 25 seems to be a plausible biogenetic precursor of gelsemine-type alkaloids which is characterized by the ring closure between C-6 and C-20. One new koumine-type alkaloid, kounaminal (32) was isolated from G. elegans. Kounaminal (32) has and acetamide residue at C-21, and is the first instance of a koumine-type alkaloid that has a residue at C-21. This kind of natural product having an aminal moiety in its molecule is quite unusual.

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To discover new antitumor natural products, we carried out the chemical investigation of the alkaloids in Gelsemium elegans and G. sempervirens (Loganiaceae), and the evaluation of the cytotoxic effects of Gelsemium alkaloids on some tumor cells. Four new gelsenicine-related alkaloids (7-10) were isolated from G. elegans. Gelsedilam (7) and 14-acetoxygelsedilam (8) are unprecedented 18,19-nor-type monoterpenoid indole alkaloids. Gelsefuranidine (9) is the first example of a monoterpenoid indole alkaloid having a furan residue on the side chain. Gelseiridone (10) is a new type of alkaloid having a nitrogen-carbon linkage between a gelsenicine-type monoterpenoid indole alkaloid that possesses an α,β-unsaturated ketone residue as well as the N_b-C20 seco-form and a monoterpene unit having an iridoid skeleton. Five new sarpagine-type alkaloids, gelsempervine-A (23), -B (24), -C (25), and -D (26), and 19Z-16-epi-voacarpine (27), and one yohimbane-type alkaloid, sempervilam (29) were isolated from G. sempervirens. Spectroscopic data suggest that 23 existed as a C/D ring-opening structure with the keto-amine form (A) in such aprotic solvents as CH_3CN, and as a transannular structure with the zwitterionic form (B) in such protic solvents as CH_3OH. The structure of sempervilam (29) was confirmed by the total synthesis. The gelsedine-type alkaloids, 14-acetoxygelsenicine (18, EC_<50>=250nM), 14,15-dihydroxygelsenicine (19), gelsedine (34), and gelsemicine (35) showed relatively strong cytotoxic effects on the A431 human epidermoid carcinoma cell line (positive control, cisplatin: EC_<50>=3.5μM).

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In the last few years, numerous new indole and oxindole alkaloids were isolated from the Chinese medicinal plant, Gelsemium elegans Benth., by us and other researchers. Our interest in the relationship of various skeletons of Gelsemium alkaloids has led us to consider their biogenetic pathway and to investigate our proposal by chemical transformations. Here, we describe the following three newly developed chemistry on the Gelsemium alkaloids. I: 3,3-Disubstituted oxindole (16) could be converted to the Na-methoxy-oxindole (20) via tungstate-catalyzed oxidation of the indoline derivative (17). This method was applied to the synthesis of the Gelsemium alkaloids, (5), (27), (28) and (56). II: Based on a biogenetic speculation, a humantenine-type Na-methoxyoxindole alkaloid, humantenirine (27), was prepared from a sarpagine-type indole alkaloid, gardnerine (21), via stereoselective rearrangement to the oxindole, olefin inversion, and introduction of a methoxy group onto the Na-function. III: 20-Hydroxydihydrorankinidine (28), a biogenetically hypothetical intermediate to the new skeletal type alkaloid, gelselegine (8) (Fig. 5), was synthesized from ajmaline (33) in 22 steps. Gardnerine (21) was transformed into the gelselegine skeleton (53), which was then converted to the natural gelsedine-type alkaloid, gelsemicine (56) in a highly stereoselective manner. Starting from 21 the first and biomimetic construction of another gelselegine-type alkaloid (60) having a hydroxy group at C-19 was achieved via a biogenetically hypothetical aziridine intermediate (59).

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Chemical investigation of Gelsemium elegans collected in Thailand resulted in the isolation of 6 new indole alkaloids, along with 7 known compounds, i.e. gelsemine(1), gelsevirine(2), koumine (3), gelsenicine(4), 14-hydroxygelsenicine(5), humantenine(6), and 14-hydroxygelsedine(7). The structures of new alkaloids, 16-epi-voacarpine(11), 19-hydroxydihydrogelsevirine(12), 19-(Z)-taberpsychine(15), koumine-N-oxide(16), gelsemine-N-oxide(18), and 19-oxo-gelsenicine(19) were determined by the spectroscopic analysis, chemical reactions, and/or X-ray analysis. Furthermore, structures of two indole alkaloids, "akuammidine" and koumidine, previously isolated from the same plants, were revised to be (8) and (10), respectively. We propose here the biosynthetic route of Gelsemium alkaloids. (Chart2) Intermediate (21) formed from strictosidine (20) will serve as a precursor of sarpagine type alkaloids, such as koumidine (10), which will be further transformed by oxidation and rearrangment into taberpsychine (15), koumine (3), humantenine (25), and gelsemine (1) alkaloids. Intermediate (21) will also be metabolized to C_<21>-norsarpagine type (22), which will be converted to the gelsedine (24) series. In order to support the biogenetic proposal above, we designed the biomimetic synthesis of koumine and humantenine skeletons from gardneria alkaloids. The synthesis of 11-methoxykoumine (30) was accomplished starting from 18-hydroxygardnerine (27) through the intramolecular C-C bond formation between the indole part (C_7) and allylic cation (C_<20>) using Pd catalysis. The biomimetic synthesis of des-N(a)-methoxyhumantenirine (35) was also achieved from gardnerine (16) in a highly stereoselective manner. Thus, OsO_4 oxidation of C/D-ring opening product (31) gave exclusively oxindole (37) which had desired configuration at C_7. (37) was further transformed into (35) via the olefine inversion process and deprotection of N(b) group.

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Highly selective cross-coupling reaction of organosilanes with organic halides and organic triflates promoted by palladium catalyst and fluoride ion is described. Organosilicon compounds like (E) - or (Z) -alkenyl, alkynyl, allyl, and arylsilanes smoothly react with alkenyl, allyl and aryl halides to give coupled products with high chemoselectivity and stereospecificity. Under similar conditions, silylation of alkenyl iodides by hexa-methyldisilane and methylation of aryl iodides by (Et₂N)₃S⁺Me₃SiF₂^- take place. The one-pot double cross-coupling of trimethylstannyl (trimethylsilyl) acetylene with two alkenyl iodides is achieved to afford isomerically pure dienynes. The cross-coupling of chiral 1-phenyl-1-trifluorosilylethane with aryl triflates occurrs stereo-specifically, providing optically active coupled products. The stereochemistry of the products is influenced decisively by reaction temperature and solvent used. A transition state model for the transmetallation step in catalytic cycle is proposed on the basis of substituent effect and stereochemical study of this reaction.

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We measured the thermal environment of green walls in one public cultural facility with large-scale green walls. It was found that the temperature of the frame of the greening unit rise as high as almost 45 degrees and the temperature fluctuated above 40°C in the daytime. This indicates that the temperature exceeds the upper limit at which plants can grow normally. After the measurement, we experimented to confirm the possibility of avoiding poor growth of green plants by adding special specifications to the existing greening frame in order to control excessive incident solar radiation.

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