N - 4909及其非对映异构体的首次全合成；一种人类肝癌Hep G2细胞中载脂蛋白E分泌的刺激剂。

First total synthesis of N-4909 and its diastereomer; a stimulant of apolipoprotein E secretion in human hepatoma Hep G2 cells.

作者信息

Yanai M, Hiramoto S

机构信息

1st Pharmaceutical Laboratory, Pharmaceutical Research Laboratories, Nisshin Flour Milling Co., Ltd., Saitama, Japan.

出版信息

J Antibiot (Tokyo). 1999 Feb;52(2):150-9. doi: 10.7164/antibiotics.52.150.

DOI:10.7164/antibiotics.52.150

PMID:10344569

Abstract

Both (R)- and (S)-3-hydroxy-13-methyltetradecanoic acids were prepared via a lipase-catalyzed enantioselective acylation. The total synthesis of N-4909 and its diastereomer were achieved by a coupling of either (R)- or (S)-3-hydroxy-13-methyltetradecanoic acid moiety with a hexapeptide moiety and by a cyclization with HATU (O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate) and HOAt (1-hydroxy-7-azabenzotriazole) in a high dilution condition. The R configuration of 3-hydroxy-13-methyltetradecanoic acid was found to be important for stimulating the activity of apolipoprotein E secretion in human hepatoma Hep G2 cells.

摘要

(R)-和(S)-3-羟基-13-甲基十四烷酸均通过脂肪酶催化的对映选择性酰化反应制备。通过将(R)-或(S)-3-羟基-13-甲基十四烷酸部分与六肽部分偶联，并在高稀释条件下用HATU（O-(7-氮杂苯并三唑-1-基)-1,1,3,3-四甲基脲六氟磷酸盐）和HOAt（1-羟基-7-氮杂苯并三唑）进行环化反应，实现了N-4909及其非对映异构体的全合成。发现3-羟基-13-甲基十四烷酸的R构型对于刺激人肝癌Hep G2细胞中载脂蛋白E的分泌活性很重要。