Total Synthesis of Swinholide A, Preswinholide A, and Hemiswinholide A

The total synthesis of synthesis of swinholide A ( 1 ) has been accomplished via key intermediate aldehyde 12 (Fig. 3), whose construction started from L‐rhamnose ( 18 ), epoxide 21 , and phenylsulfone orthoester 22 , and proceeded through an Enders asymmetric alkylation ( 16 + 17 → 15 ), a Ghosez cyclization ( 21 + 22 → 20 ), and a Corey‐Sharpless coupling reaction ( 13 + 14 → 12 ). Elaboration of compound 12 along slightly different pathways culminated in the synthesis of carboxylic acid 10 and hydroxy compound 11 , whose union by an esterification reaction, followed by ring closure of the subsequently derived hydroxy acid under Yamaguchi conditions, led to swinholide A ( 1 ) upon deprotection. The chemistry developed also allowed the total synthesis of preswinholide A methyl ester ( 7 ), preswinholide A ( 8 ), and hemiswinholide A ( 78 ).