AN EFFICIENT SYNTHESIS OF LTD4 ANTAGONIST L-699,392

被引：108

作者：

KING, AO ^{[1
]}

CORLEY, EG ^{[1
]}

ANDERSON, RK ^{[1
]}

LARSEN, RD ^{[1
]}

VERHOEVEN, TR ^{[1
]}

REIDER, PJ ^{[1
]}

XIANG, YB ^{[1
]}

BELLEY, M ^{[1
]}

LEBLANC, Y ^{[1
]}

LABELLE, M ^{[1
]}

PRASIT, P ^{[1
]}

ZAMBONI, RJ ^{[1
]}

机构：

[1] MERCK & CO INC,MERCK FROSST CTR,POINTE CLAIRE H9R 4P8,PQ,CANADA

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1993年 / 58卷 / 14期

关键词：

D O I：

10.1021/jo00066a027

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The asymmetric synthesis of L-699,392 (1) [3-[[(1S)-[3(E)-[2-(7-chloroquinolinyl)ethenyl]phenyl]-3-(acetylphenyl)propyl]thiol-2(S)-methylpropanoic acid], a leukotriene antagonist, is accomplished in six steps starting from the monoaldehyde 2. The main framework of the molecule is formed via a Pd-catalyzed Heck reaction. The asymmetric center is introduced via the chiral reduction of the ketone 4 using optically active B-chlorodiisopinocampheylborane (10) derived directly from chloroborane and (-)-alpha-pinene. A very high asymmetric amplification is observed in which 95 % ee product can be obtained from 70% optically pure a-pinene. Reagent 17, which is prepared in situ from methylmagnesium chloride and 2 equiv of lithium hexamethyldisilazide, is used to convert the methyl ester 5 to the methyl ketone 6 in one step with essentially no impurities formed under the reaction conditions. The thio side chain is finally incorporated by the displacement of the chiral mesylate 7 with complete inversion at the chiral center. The overall yield for the sequence is 42%.

引用

页码：3731 / 3735

页数：5

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