Synthesis of ultra-short-acting neuromuscular blocker GW 0430: A remarkably stereo- and regioselective synthesis of mixed tetrahydroisoquinolinium chlorofumarates

被引：39

作者：

Samano, V ^{[1
]}

Ray, JA ^{[1
]}

Thompson, JB ^{[1
]}

Mook, RA ^{[1
]}

Jung, DK ^{[1
]}

Koble, CS ^{[1
]}

Martin, MT ^{[1
]}

Bigham, EC ^{[1
]}

Regitz, CS ^{[1
]}

Feldman, PL ^{[1
]}

Boros, EE ^{[1
]}

机构：

[1] Glaxo Wellcome, Res & Dev, Dept Chem, Res Triangle Pk, NC 27709 USA

来源：

ORGANIC LETTERS | 1999年 / 1卷 / 12期

关键词：

D O I：

10.1021/ol9911573

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

[GRAPHICS] The stereo- and regioselective synthesis of ultra-short-acting nondepolarizing neuromuscular blocker GW 0430 (5a) is described. Key steps involved the enantioselective transfer hydrogenation of imine 8 employing Noyori's catalyst, the stereoselective crystallization and methanolysis of trans-betaines 11 and 12, and the stereo- and regioselective trans elimination of hydrogen chloride from 14, The latter transformation allowed complete control of the position of the chloro substituent and stereochemistry at the double bond of the linker in 15.

引用

页码：1993 / 1996

页数：4

共 22 条

[1] ENANTIOSPECIFIC SYNTHESIS OF 3-SUBSTITUTED ASPARTIC ACIDS VIA ENZYMIC AMINATION OF SUBSTITUTED FUMARIC ACIDS [J].

AKHTAR, M ;

BOTTING, NP ;

COHEN, MA ;

GANI, D .

TETRAHEDRON, 1987, 43 (24) :5899-5908

[2] NEWER NEUROMUSCULAR BLOCKING-AGENTS [J].

BEVAN, DR .

PHARMACOLOGY & TOXICOLOGY, 1994, 74 (01) :3-9

[3] Bis- and mixed-tetrahydroisoquinolinium chlorofumarates: New ultra-short-acting nondepolarizing neuromuscular blockers [J].

Boros, EE ;

Bigham, EC ;

Boswell, GE ;

Mook, RA ;

Patel, SS ;

Savarese, JJ ;

Ray, JA ;

Thompson, JB ;

Hashim, MA ;

Wisowaty, JC ;

Feldman, PL ;

Samano, V .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (02) :206-209

[4] SYNTHESIS AND ABSOLUTE CONFIGURATION OF CRYPTOSTYLINES I, II, AND III [J].

BROSSI, A ;

TEITEL, S .

HELVETICA CHIMICA ACTA, 1971, 54 (06) :1564-&

[5]

COX A, 1979, COMPREHENSIVE ORGANI, P685

[6] NUCLEAR MAGNETIC-RESONANCE AND X-RAY STEREOCHEMICAL STUDIES ON 1-BENZYLTETRAHYDROISOQUINOLINIUM SALTS [J].

ELSAYAD, HA ;

SWARINGEN, RA ;

YEOWELL, DA ;

CROUCH, RC ;

HURLBERT, S ;

MILLER, RW ;

MCPHAIL, AT .

JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1982, (09) :2067-2077

[7] PROTON NUCLEAR MAGNETIC RESONANCE SPECTRA OF SUBSTITUTED SUCCINIC ANHYDRIDES ACIDS SALTS AND ESTERS [J].

ERICKSON, LE .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1965, 87 (09) :1867-&

[8] PREPARATION OF 1-(3',1'H,6'-PYRIDAZINONE)-3,6-PYRIDAZINEDIONE - ATTEMPTS TO PREPARE BICYCLIC DIMALEIC HYDRAZIDE [J].

FEUER, H ;

RUBINSTEIN, H .

JOURNAL OF ORGANIC CHEMISTRY, 1959, 24 (06) :811-813

[9] VICINAL DIOL CYCLIC SULFATES - LIKE EPOXIDES ONLY MORE REACTIVE [J].

GAO, Y ;

SHARPLESS, KB .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1988, 110 (22) :7538-7539

[10] DIRECT TRANSFORMATION OF DIALKYL SULFATES INTO ALKYLLITHIUM REAGENTS BY A NAPHTHALENE-CATALYZED LITHIATION [J].

GUIJARRO, D ;

GUILLENA, G ;

MANCHENO, B ;

YUS, M .

TETRAHEDRON, 1994, 50 (11) :3427-3436

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