Stereocontrolled and convergent total synthesis of amphidinolide T3.
Stereocontrolled and convergent total synthesis of amphidinolide T3 has been described. A retrosynthetic scheme was constructed that led to the recognition of readily available and enantiomerically related compounds as starting materials for the total synthesis of amphidinolide T3. Thus, the two key building blocks 6 and 7 were defined as subtargets and synthesized in optically active forms. The C1-C12 fragment 6 was derived from commercially available D-glutamic acid or its synthetically equivalent (R)-5-hydroxymethyltetrahydrofuran-2-one 16 as starting material involving highly diastereoselective asymmetric allylation as a key step. The C13-C21 fragment 7 was efficiently synthesized in high yield through the dithiane coupling of the segment 10 and iodide 11, followed by subsequent deprotection and Petasis olefination. Eventually, assembly of the fragment aldehyde 6 and dithiane 7 along with C-C bond formation, a two-step oxidation-reduction sequence, selective macrolactonization, and functional transformation furnished the convergent total and formal synthesis of amphidinolide T3 and T4, and this approach also provides a flexible and practical synthesis of amphidinolide T macrolides.
Deng
Li-Sheng
LS
Laboratory of Modern Organic Synthetic Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai, 200032, PR China.
Huang
Xiao-Ping
XP
Zhao
Gang
G
D018698:Glutamic Acid / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis*; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D000097442:Amphidinolides
D018698:Glutamic Acid; D018942:Macrolides; C414522:amphidinolide T; D000097442:Amphidinolides