Synthetic Studies on Cembranolides. Stereoselective Synthesis of a Crassin Acetate Synthon

Article abstract of DOI:10.1021/jo00343a018

A stereoselective synthesis of the lactone tetrol derivative 21, a possible synthetic precursor of the cembranolide crassin acetate (1), is described.The cycloheptenone 5 provides the requisite seven-carbon chain of tetrol 21.The acetic acid moiety was introduced via alkylation with ethyl iodoacetate followed by saponification.Selenolactonization of the resulting keto acid afforded lactone 8, which was reduced to hydroxy lactone 9.Protection as the silyl ether 10 and oxidation with m-chloroperoxybenzoic acid and then treatment with acetic anhydride yielded the rearranged acetate 13.Selenoxide elimination gave enol acetate 14, which was brominated and dehydrobrominated to the enone 18.Addition of lithium tetramethylalanate gave the alcohol 19 as the sole stereoisomer.Protection as the (methoxyethoxy)methyl ether 20 followed by ozonolysis and borohydride reduction afforded the desired diol 21 as a crystalline substance.The structure of this intermediate was confirmed by single-crystal X-ray analysis.