Synthesis and biological testings as inhibitors of HMGCoA reductase of theseco-acid of tuckolide and its C-7 epimer

The seco-acid of the natural macrolactone, tuckolide (decarestrictin D) and the C-7 epimer have been prepared in enantiomerically pure form from D-glu conolactone and poly(3-hydroxy butyric acid). The key steps are Horner-Emmo ns olefination and stereoselective reduction of the resulting enone to prov ide both epimers at C-7. None of the seco-acids inhibit microsomal HMGCoA r eductase of pea or rat liver. It may be concluded that the cholesterol bios ynthesis inhibiting effect of tuckolide is unlikely to proceed via HMGCoA r eductase inhibition. (C) 1999 Elsevier Science Ltd. All rights reserved.