Total synthesis of the antitumor acetogenin mosin B: desymmetrization approach to the stereodivergent synthesis of threo/trans/erythro-type acetogenins.
A total synthesis of the threo/trans/erythro-type acetogenin mosin B and one of its diastereomers has been achieved. The carbon skeleton is assembled in a convergent fashion from two segments (a THF ring segment and a gamma-lactone segment) through the Nozaki-Hiyama-Kishi reaction. The THF ring segment was stereoselectively constructed by a stereodivergent synthesis starting from a common intermediate (4-cyclohexene-1,2-diol) based on a desymmetrization strategy. The gamma-lactone segment was synthesized by coupling a triflate and a chiral alpha-sulfenyl gamma-lactone. By virtue of these synthetic results, we suggest that the absolute configuration of natural mosin B is 1 a. Antiproliferative effects of 1 a and 1 b were also investigated.
Maezaki
Naoyoshi
N
Graduate School of Pharmaceutical Sciences Osaka University, 1-6 Yamadaoka, Suita Osaka 565-0871, Japan.
Kojima
Naoto
N
Sakamoto
Atsunobu
A
Tominaga
Hiroaki
H
Iwata
Chuzo
C
Tanaka
Tetsuaki
T
Monden
Morito
M
Damdinsuren
Bazarragchaa
B
Nakamori
Shoji
S
D000972:Antineoplastic Agents, Phytogenic / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015394:Molecular Structure; D010190:Pancreatic Neoplasms / Q000473:pathology; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D000972:Antineoplastic Agents, Phytogenic; D005663:Furans; D007783:Lactones; C107769:mosin B