Stereodivergent syntheses of diospongins A and B

Syntheses of the tetrahydropyranol natural products (+/-)-diospongin A and (+/-)-diospongin B, in four steps (37 % overall) and seven (14 % overall) or nine steps (25 % overall) respectively, are reported. A common homoallylic alcohol serves as a key intermediate for stereodivergent, one-pot olefin metathesis/deprotection/oxa-Michael cyclization steps that establish the requisite 2,6-stereochemical relationships of the diastereomeric targets. Cross metathesis results in formation of an acyclic, unsaturated ketone that undergoes conjugate addition to give diospongin A directly. Ring-closing metathesis/conjugate addition provides a diastereomerically pure bicyclic lactone, possessing the contra-thermodynamic 2,6-trans stereochemistry, that can be converted to diospongin B in either two or four steps.