Drimanes synthesis

Heterocycles in synthesis of drimane sesquiterpenoids from labdane diterpenoids 97IZV896. 

Sesquiterpenoids possessing the drimane skeleton (22) exhibit an impressive series of biological properties. Recently, all aspects relative to occurrence [76], biological activity [76], insect antifeedant properties [77] and synthesis [78] of these terpenoids have been exhaustively reviewed. 

TOTAL SYNTHESIS OF BIOLOGICALLY INTRIGUING DRIMANE-TYPE SESQUITERPENOIDS VIA INTRAMOLECULAR DIELS-ALDER APPROACHES... 

Atdehyde-enolate hydroxylation. Enolate hydroxylation has been extended to, the aldehyde 1 by Tanis and Nakanishi in a total synthesis of the drimanic sesquiterpene ( )-warburganal (3). Thus treatment of 1 with LD A in THF at - 78°C followed by M0O5 -HMPT (1.5 equiv.) affords 2 in 85% yield. 

Acyclic dienamines are relatively unstable, but very reactive towards electron-poor dienophiles as describe in a review article (1984). A more recent example shows the preparation of sterically encumbered 1-amino-1,3-diene (125) and its, nevertheless, efficient and highly stereoselective [4 + 2] cycloaddition to dimethyl fumarate (Scheme 32). Elimination of pyrrolidine, by heating the non-iso-lated cycloadduct with acetic anhydride, afforded hexahydronaphth ene (126), a key intermediate for a synthesis of drimane-type sesquiterpenes. 

Uvidins are attractive chiral starting materials for the synthesis of highly oxidized biologically active drimane-like sesquiterpenes as demonstrated by the syntheses of natural (-)-cinnamodial (115) and (-)-cinnamosmolide (116) from uvidin A (3.14),... 

The total synthesis of the antimicrobial drimane-type sesquiterpene (-)-pereniporin A was achieved by the research team of K. Mori. The advanced intermediate bicyclic primary alcohol was first oxidized to the corresponding aldehyde using the Moffatt oxidation. Interestingly, the sensitive a-hydroxy aldehyde moiety in the product remained unchanged. The final step was a global deprotection followed by a spontaneous lactol formation. 

The diverse biological activity (e.g. insect antifeeding, plant growth regulation, molluscicidal) of a number of drimane sesquiterpenoids has stimulated considerable interest in their synthesis and the year under review has seen many new developments and improvements. Much of the synthetic work has centred around the key bicyclic diester (54) derived from 1-vinyl-2,6,6-trimethylcyclohexene and dimethyl acetylenedicarboxylate. In contrast to earlier results,34 Ley et al.8S... 

Follotving the quite recent discovery of the broad range of biological activities exhibited by members of the sesquiterpene-based drimane family, namely mnio-petals, kuehneromycins, and marasmanes, a solid-phase approach towards a common key intermediate has recently been disclosed [408]. This supported synthesis offers the additional advantage of potential access to libraries of compounds with the same sesquiterpenoid skeleton. 

Jendrzejewski, S., and Ermann, P., Total synthesis of restricticin. Tetrahedron Lett., 34, 615, 1993. Weyerstahl, P., Schwieger, R., Schwope, I., and Hashem, M.A., Synthesis of some naturally occuring drimane and dinorlabdane derivatives, Liebigs Amn. Org. Bioorg. Chem., 1389, 1995. 

Total Synthesis of Biologically Intriguing Drimane-Type Sesquiterpenoids Via Intramolecular Diels-Alder Approaches... 

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