This article reviews generally the synthetic studies on limonoids, a large group of natural products with highly oxidized cyclic terpenoid structures, and related compounds. Recent interest on insect antifeedant and growth disrupting activity of limonoid compounds, specially of azadirachtin (17), gave an impetus to the synthetic investigations : Due to the complex structural elements involved, total synthetic works are very limited, the achievement having been reported only one case for the synthesis of an intact-ring limonoid, azadiradione (6). The synthetic studies on 17 are also under way, which represent a formidable challenge because of its utmost structural complexity. As a prelude to the total synthesis or with the aim of biological studies, a number of investigations have been carried out on the syntheses of degraded limonoids, and compounds with partial structure units of limonoids, which are mostly their CDE-ring analogs. These studies in conjunction with the partial syntheses of other ring structures have brought much progress in the methods for the construction of the unique structural units involved in limonoids.
Enantiospecific total syntheses of (+) -eremantholide A (6) and (-) -verrucarol (41) are described. Both total syntheses began with our enantiopure building block 1, which was prepared from D-glucose. The total synthesis of 6 features (1) regio- and stereoselective radical carbocyclization applied to 16, and (2) nine-membered ring formation by the coupling reaction of the A/B ring equivalent 35 with 3 (2H) -furanone 8 followed by a vinylogous aldol reaction applied to 38. The key steps for the total synthesis of 41 are (1) intramolecular Knoevenagel cyclization applied to 48, (2) construction of the consecutive quaternary carbon center by sequential alkylation and aldol reaction applied to γ-lactone 54, and (3) a skeletal rearrangement applied to 68β for the trichothecene ring system construction.
This mini review deals with the synthesis and their properties of a new type of nucleosides, so-called C-azanucleosides, along with the synthetic method for their related compounds, azafuranopentose. The DNA and RNA have been known to play an important role in the protein synthesis and the life processes. The azanucleosides seem very attractive to scientists as a new class of DNA and RNA subunit compounds.
Recently we found that various titanium-carbene complexes were produced by the desulfurization of thioacetals with the low-valent titanium species Cp2Ti [P (OEO)3] 2. This article deals with their application to organic synthesis including some guiding conceptions of the study. Desulfurization of thioacetals prepared from α, β-unsaturated aldehydes or 1, 3-bis (phenylthio) propene derivatives in the presence of 1-olefins afforded alkenylcyclopropanes. The intermediates of this reaction, vinylcarbene complexes, reacted with carbonyl compounds to afford the Wittig-like olefination products in good yields. The similar carbonyl olefination using various types of thioacetals and orththioformates with carbonyl compounds including carboxylic acid derivatives also produced a variety of olefins. Furthermore the alkylidenetitanocenes formed from saturated thioacetals reacted with organic molecules having a carbon-carbon multiple bond. When they were treated with alkynes, conjugated dienes were produced with high stereoselectivity. The reaction with allyltrialkylsilanes afforded (Z) -γ-substituted allylsilanes via the formation of titanacyclobutane intermediates. We also found the first [2+1] carbenoid insertion reaction of titanium-carbene complexes with trialkylsilanes and related group 14 organometallics.
A novel rearrangement of 1- (1-alkynyl) cyclopropanols to 2-cyclopenten-1-ones proceeded on complexation of their alkynyl part with Co2 (CO) 8. In the case of reactions of 1-alkynylcyclopropanols with an alkyl substituent on the cyclopropane ring, either 4-substituted or 5-substituted 2-cyclopenten-1-ones could be selectively obtained by appropriate choice of stereochemistry and protective group of the substrates. This rearrangement was successfully applied to the annulation of cyclopentenones onto cycloalkenes. Furthermore, the rearrangement was found to proceed catalytically on addition of triarylphosphite as a ligand. The same type of rearrangement proceeded when 1- [o- (1-alkynyl) phenyl] cyclopropanols were employed as substrate ; these being converted to 2, 3-dihydro-l-naphthalenone derivatives on heating their Co2 (CO) 6 complexes in 2-propanol. Furthermore, a new type of isomerization-cyclization reaction proceeded to give 3a, 4-dihydro-3 H-cyclopenta [a] inden-2-one derivatives when the same reaction was carried out in the presence of DABCO. Finally a novel transformation of 1-allenylcyclopropanols into substituted 1, 4-hydroquinones was developed utilizing the interaction of 1, 2-propadienes and Co2 (CO) 8. This reaction was applied to the synthesis of vitamin E and K analogs.
(Diene) Fe (CO) 3 complexes enjoy widespread use in organic synthesis, because they are synthetically equivalent to free dienes, yet are more stable and possess markedly different chemical properties. Complexation and decomplexation of diene Fe (CO) 3 compounds is readily accomplished and provides high yields in most cases. In addition, unsymmetrically substituted dienes are prochiral and, therefore, the corresponding Fe (CO) 3 complexes, are chiral. Considerable attention has been directed toward the efficient use of this temporally introduced chirality to construct neighboring stereogenic centers. Indeed, this is the main subject of Fe (CO) 3 complex chemistry, along with research on a practical method for synthesizing chiral (diene) Fe (CO) 3 complexes. Another fascinating aspect of these complexes is the mobility of the Fe (CO) 3 unit, which has received less attention than its stereodirecting ability. The Fe (CO) 3 moiety, which attaches to dienyl compounds by coordination, can move one carbon unit accompanied by isomerization of the diene via a η5 cation intermediate (1, 2-migration). This article presents the recent studies on iron tricarbonyl units to control the regio- and stereochemistry of nucleophilic addition to a neighboring C=X (X=O, N) double bond and η5- (pentadienyl) iron (+1) cation complex.
Current progress on glycobiology and glycotechnology urge the development of various new drugs. As an example of the applicable studies based on the carbohydrate chemistry, there is the drug design of selectin antagonists which block the interaction between the selectin and its natural ligand, sialyl Lewis X (sLeX). The highly effective synthesis of sLeX is one of the important things for the investigation of selectin antagonists, for example, to establish a high-throughput screening (HTS) of active compounds. As a result, we succeeded the highly practical synthesis of sLeX pentasaccharide and discovered a potent selectin antagonist, GSC-150, using the HTS. In addition, in order to establish a large scale synthesis of GSC-150, a one-pot glycosylation characterized by “Armed-Disarmed Coupling” was developed. This glycosylation was an applicable method for the synthesis of various LeX analogs.