Enantioselective total synthesis of octalactin a using asymmetric aldol reactions and a rapid lactonization to form a medium-sized ring.
Octalactin A, an antitumor agent containing an eight-membered lactone moiety, has been stereoselectively prepared by means of enantioselective aldol reactions of selected silyl enolates with achiral aldehydes, promoted by a chiral Sn(II) complex. The medium-sized lactone part was effectively constructed by way of a new and rapid mixed-anhydride lactonization using 2-methyl-6-nitrobenzoic anhydride (MNBA) with a catalytic amount of 4-(dimethylamino)pyridine (DMAP) or 4-(dimethylamino)pyridine 1-oxide (DMAPO). The use of only 5 mol % of DMAP or 2 mol % of DMAPO rapidly promoted formation of the medium-sized ring of the octalactin, demonstrating the remarkable efficiency of the new lactonization protocol.
Shiina
Isamu
I
Department of Applied Chemistry, Faculty of Science, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan. shiina@ch.kagu.tus.ac.jp
Hashizume
Minako
M
Yamai
Yu-suke
YS
Oshiumi
Hiromi
H
Shimazaki
Takahisa
T
Takasuna
Yu-ji
YJ
Ibuka
Ryoutarou
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D007783:Lactones; C509477:cephalosporolide D; C509476:octalactin A; C509475:octalactin B