(Z)-5-(4-Fluorophenyl)pent-4-enoic Acid: A Precursor for Convenient and Efficient Synthesis of the Antihypercholesterolemia Agent Ezetimibe

被引：12

作者：

Sova, Matej ^{[1
]}

Mravljak, Janez ^{[1
]}

Kovac, Andreja ^{[1
]}

Pecar, Slavko ^{[1
,3
]}

Casar, Zdenko ^{[2
]}

Gobec, Stanislav ^{[1
]}

机构：

[1] Univ Ljubljana, Fac Pharm, Ljubljana 1000, Slovenia

[2] Lek Pharmaceut Dd, Sandoz Dev Ctr Slovenia, API Dev, Dept Organ Synth, Menges 1234, Slovenia

[3] Jozef Stefan Inst, Ljubljana 1000, Slovenia

来源：

SYNTHESIS-STUTTGART | 2010年 / 20期

关键词：

cholesterol absorption inhibitor; (Z)-5-(4-fluorophenyl)pent-4-enoic acid; Wittig reaction; azetidinone; asymmetric synthesis; CHOLESTEROL ABSORPTION INHIBITORS; PRIMARY HYPERCHOLESTEROLEMIA; OXIDATION; OLEFINS;

D O I：

10.1055/s-0030-1258193

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

A convenient and efficient total synthesis of ezetimibe, an intestinal cholesterol absorption inhibitor and useful anticholesteremic agent, is described. Based on (Z)-5-(4-fluorophenyl)pent-4-enoic acid as a starting compound, and taking the synthesis through further Z-configured intermediates, the total yield is remarkably increased, compared with the use of the corresponding E-configured starting substances or intermediates.

引用

页码：3433 / 3438

页数：6

共 38 条

[1]

ALLEGRINI P, 2008, Patent No. 20072013

[2] Effectiveness and tolerability of ezetimibe in patients with primary hypercholesterolemia: Pooled analysis of two phase II studies [J].

Bays, HE ;

Moore, PB ;

Drehobl, MA ;

Rosenblatt, S ;

Toth, PD ;

Dujovne, CA ;

Knopp, RH ;

Lipka, LJ ;

LeBeaut, AP ;

Yang, B ;

Mellars, LE ;

Cuffie-Jackson, C ;

Veltri, EP .

CLINICAL THERAPEUTICS, 2001, 23 (08) :1209-1230

[3]

Bodi J., 2007, [No title captured], Patent No. [WO 2007/072088, 2007072088]

[4] Synthesis of iodinated biochemical tools related to the 2-azetidinone class of cholesterol absorption inhibitors [J].

Burnett, DA ;

Caplen, MA ;

Domalski, MS ;

Browne, ME ;

Davis, HR ;

Clader, JW .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2002, 12 (03) :311-314

[5]

DU H, 2009, Patent No. 101423515

[6]

Escude A., 2007, Process for preparing ezetimibe and intermediate compounds useful for the preparation thereof, Patent No. [WO 2007/144780, 2007144780]

[7]

HUANG Z, 2009, Patent No. 101423511

[8]

Janez M., 2010, [No title captured], Patent No. [WO 2010/012775, 2010012775]

[9]

Kansal KK, 2007, Patent WO, Patent No. [2007/120824 A2, 2007120824]

[10] Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia [J].

Knopp, RH ;

Gitter, H ;

Truitt, T ;

Bays, H ;

Manion, CV ;

Lipka, LJ ;

LeBeaut, AP ;

Suresh, R ;

Yang, B ;

Veltri, EP .

EUROPEAN HEART JOURNAL, 2003, 24 (08) :729-741

← 1 2 3 4 →