Enantioselective Synthesis of Xanthatin

The enantioselective synthesis of cytostatic and antibiotic xanthatin (1a) is reported. As a key intermediate, a bicyclic compound 2 was identified, which can be readily synthesized from methyl-2-furoic acid in diastereo- and enantiomerically pure form. Compound 2 can be functionalized regio- and stereoselectively at C-6 and C-7, allowing the facile introduction of the functionalities found in xanthatin, as well as the synthesis of derivatives thereof. Moreover, a robust strategy for the introduction of the exo-methylene group at C-3, commonly found in many sesquiterpenes, was developed that makes use of masking the alkene in the alpha,beta-unsaturated carbonyl system by O-pivaoyl, which is stable under acidic and mild basic conditions but eliminated upon treatment with strong bases.