Synthesis of Diterpenoids

The synthesis of tricyclic compounds based on the cyclisation of methyl geranyl-geranoate was described eighteen years ago. However, the discovery of expoxy-squalene as an intermediate in steroid biosynthesis, and the corresponding in vitro cyclisation experiments, have re-awoken interest in this area of diterpene synthesis. The structural and stereochemical course of the in vitro cyclisation of the epoxy-trans-olefin (138) has been studied. Two A/B-trans-fused tricyclic compounds (139) and (140) have been isolated. The levantenolides (142) and (143) have been obtained by two closely related routes. In the first, the butenolide (141), derived from monocyclofamesyl bromide, afforded the a- and P levantenolides (142) and (143) on cyclisation with stannic chloride. In the second, the corresponding acyclic butenolide derived from famesyl bromide was cyclised. 

The stereospecific synthesis of the C-4 epimeric diterpenoid resin acids has attracted considerable attention. Methylation of the keto-nitrile (144) gives a product possessing an equatorial methyl group, in contrast to methylations of 

Tanemura, T. Suzuki, and Y. Kitahara, Chem. Comm., 1970, 28. 

3-steric interactions should be diminished. Finally, the peri interactions with C-6 exist in the esters, but not in the nitriles. 

The synthesis of several aromatic tricyclic 20-norditerpenoids has been described. The key acid (146) was prepared by cyclisation of (145). The various a/b stereoisomers were prepared from this by catalytic or dissolving metal 

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Surveys of recent developments in the chemistry of C2o diterpenoid alkaloids,4 of the alkaloids of Consolida ambigua,5 and of the synthesis of diterpenoid alkaloids by thermolysis6 have appeared. 

Synthesis of diterpenoids containing O-heterocyclic fragments 91MI41. 

In addition to several newly reported diterpenoid alkaloids, the structures of some forty alkaloids have been revised on the basis of recent work. The structures presented in this Report have been revised from those reported in the literature to reflect these recent corrections. The level of efforts directed toward the synthesis of diterpenoid alkaloids was substantially reduced this year, with only a description of the synthesis of napelline by Professor Wiesner s group appearing. No reports of new work on the Daphniphyllum diterpenoid alkaloids were available to our laboratories. 

P. Quayle and co-workers utilized the Dotz benzannulation reaction for the synthesis of diterpenoid quinones." The authors developed a novel synthetic approach to 12-O-methyl royleanone using a simple vinyl chromium carbene complex along with a disubstituted oxygenated acetylene. The bicyclic hydrazone was converted to the corresponding vinyllithium derivative by the Shapiro reaction and then functionalized to give the desired crude Fischer chromium carbene complex. The benzannulation took place in refluxing THF with excellent regioselectivity, and the natural product was obtained in 37% overall yield from the hydrazone. 

Synthetic applications of the elimination of allylic carbonates have been reported by other groups,including steps in the synthesis of diterpenoid forskolint ° and triterpenoid azadirachtinP Asymmetric eliminations have been exploredP ... 

Allenes have been added to many cyclic a,/8-unsaturated ketones to give methylenecyclobutane derivatives. The stereochemistry of such additions has been rationalized by Wiesner, who has used the method extensively in the synthesis of diterpenoid alkaloids. For example, the synthesis (Scheme 10) of talatisamine (39) involved the cycloaddition of allene to the enone (35) to give the photoadduct (36) which was converted into the masked aldol (37). Retro-aldol reaction followed by another aldol cyclization gave (38) which was converted into talatisamine (39). Intramolecular photocyclizations of appropriate allenic enones can also be expected to be synthetically useful. The formation of (41) from (40) in high yield is a promising reaction. A closely related process is the cyclization of (42) to (43) (Scheme 11). ... 

A straightforward synthesis of seven-membered carbo-cycles, based on titanocene(III)-catalyzed radical cycliza-tions, was used for the inter alia synthesis of diterpenoid valparane." The titanocene (Ill)-mediated radical cascade of 165 involves consecutive 6-endo, 6-endo, and 1-endo cyclizations to give 166 (Scheme 25.76). 

Total Synthesis of Diterpenoid Pyrones, Nalanthalide, Sesquicillin, Candelalides A-C, and Subglutinols A, B... 

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