Absolute stereochemistries and total synthesis of (+)/(−)-macrosphelides, potent, orally bioavailable inhibitors of cell–cell adhesion

In the current studies, we used the single-crystal X-ray analysis and Kakisawa–Kashman modification of the Mosher NMR method to determine the complete relative and absolute stereochemistries of the (+)-macrosphelides A (+)-1 and B (+)-2 . The stereostructure of (+)-2 was determined by chemical comparison with artificial (+)-2 from (+)-1 . We also report the convergent total synthesis of (+)-1 and (+)-3 , as well as their antipodes, utilizing an asymmetric dihydroxylation for introduction of chirality and Yamaguchi macrocyclization to form the 16-membered trilactone macrolides.