Enantioselective syntheses of rigidiusculamides A and B: revision of the relative stereochemistry of rigidiusculamide A.
The first enantioselective synthesis of cytotoxic natural products rigidiusculamides A (ent-21) and B (8) has been achieved by two synthetic routes. The first one is convergent based on the common intermediate 11, obtained through a high yielding SmI(2) -mediated Reformatsky-type reaction. A highly diastereoselective one-pot Dess-Martin periodinane-mediated bis-oxidation allowed the direct conversion of the diastereomeric mixture of 11 into rigidiusculamide B (8). Isolation of minor diastereomer 21, in combination with computational work, allowed us to suggest the structure of the natural rigidiusculamide A to be ent-21, as synthesized by the second route. Four diastereomers (7, ent-7, 22a, and 22b) and an enantiomer (21) of rigidiusculamide A (ent-21) have been synthesized. On the basis of literature precedents and computational work, a biosynthetic pathway for rigidiusculamides A and B was proposed to account for the opposite configuration at C-5 of those two congeners.
Department of Chemistry and Key Laboratory for Chemical Biology of Fujian Province, College of Chemistry and Chemical Engineering, Xiamen University, Xiamen, Fujian 361005, PR China.
Gui-Yang
GY
Chen
Huang
H
Huang
Jian-Liang
JL
Ye
Ai-E
AE
Wang
Hui-Ying
HY
Huang
Hong-Kui
HK
Zhang
Pei-Qiang
PQ
Huang
D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D011789:Quantum Theory; D013237:Stereoisomerism
D001688:Biological Products; D011759:Pyrrolidines; C572786:rigidiusculamide A