Enantiospecific formal total synthesis of homogynolide-A

2001 ARKIVOC  
Formal total synthesis of both enantiomers of homogynolide-A, a sesquiterpene containing an αspiro-β-methylene-γ-butyrolactone moiety fused to a bicyclo[4.3.0]nonane framework, is described. Thus, (R)-carvone was converted into both enantiomers of 3-methylcarvone 14. A reductive allylation, Wacker oxidation and intramolecular aldol condensation sequence transformed 3-methylcarvone into the hydrindanone 18. Regiospecific reduction of the enone followed by a three step degradation of the
more » ... ion of the isopropenyl group converted the hydrindanone 18 into the dione 21, which on regioselective ketalisation furnished the key intermediate ketoketal 13. Methoxymethylene Wittig reaction followed by bromoacetalisation reaction transformed the ketoketal 13 into the bromoacetal 23. The 5-exo-dig radical cyclisation of the bromoacetal 23 followed by the hydrolysis and oxidation of the resultant spiroacetal 24 furnished a 1:4 mixture of the Greene's precursor ketospirolactone 12 and its spiroepimer 26. (Trogoderma granarium, Tribolium confusum). 5 The structures of homogynolides-A 1 and B 2 were established as the angelyl ester of 2-hydroxybakkenolide-A and tiglyl ester of 3-hydroxybakkenolide-A, respectively, via chemical degradation and spectral comparison with other bakkenolides. The unusual structural features of homogynolides coupled with their associated biological activities made them attractive and challenging synthetic targets. Despite their biological properties, homogynolides and bakkenolides have received only a limited attention from synthetic chemists. 6-9 Only one approach by Greene and co-workers was reported in the literature for the total synthesis of homogynolides-A and B prior to the initiation of work in our laboratory, and after the completion of our synthesis, 9 Mori and Matsushima 7c have reported the total synthesis of (-)-homogynolide-A.
doi:10.3998/ark.5550190.0002.802 fatcat:xrhfwhzh2jccvdij56zzgkxrva