Total synthesis of amphidinolide T3 using ring-closing metathesis and asymmetric dihydroxylation strategy

Total synthesis of amphidinolide T3, a 19-membered ring marine macrolide, has been accomplished using a ring-closing metathesis (RCM) and asymmetric dihydroxylation (AD) strategy. A cycloalkene having the C12=C13 double bond was assembled via RCM in 80% yield and in E/Z ratio of 76:24. The (12E)-isomer -underwent AD using 1 mol% K₂OsO₂(OH)₄ and 4 mol% (DHQD)₂AQN as the chiral catalyst at 0 C for 15 hours, furnishing the desired (12R,13R)-diol and its (12S,13S)-diastereomer in 59% and 25% yields, respectively. Selective monosilylation of (12R,13R)-diol followed by DMP oxidation and desilylation afforded amphidinolide T3 in 3.4% overall yield via a 15-step sequence.