Total synthesis of aspergillide B and structural discrepancy of aspergillide A

Fourteen-membered cytotoxic macrolides 1 and 2 were synthesized from alcohol 10 in 15 steps utilizing stereospecific Pd(II)-catalyzed cyclization of ζ-hydroxy chiral allylic alcohol 7. Aspergillides A and B were isolated from marine fungus, and their structures were proposed as 1 and 2, respectively. The synthetic 1 was not matched with aspergillide A but matched with aspergillide B. The chiral center at C-13 position of aspergillide B was revised to be (S)-configuration. The key steps of the stereoselective synthesis include the Sharpless asymmetric dihydroxylation, cross-metathesis, stereospecific construction of tetrahydropyran ring of 16 using PdII catalyst, and the Yamaguchi macrolactonization.

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