Synthesis of CC-1065 and duocarmycin analogs via intramolecular aryl radical cyclization of a tethered vinyl chloride

被引：50

作者：

Boger, DL

Boyce, CW

Garbaccio, RM

Searcey, M

机构：

[1] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA

[2] Scripps Res Inst, Skaggs Inst Chem Biol, La Jolla, CA 92037 USA

来源：

TETRAHEDRON LETTERS | 1998年 / 39卷 / 16期

关键词：

D O I：

10.1016/S0040-4039(98)00232-9

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

The 5-ero-trig radical cyclization of an aryl halide onto a tethered vinyl chloride produces the 3-chloromethyl dihydroindole precursors for CC-1065 and duocarmycin analogs with chlorine installed as a suitable leaving group for subsequent cyclopropane spirocyclization. The generality of this approach was examined in the context of six CC-1065 and duocarmycin analogs previously synthesized in this laboratory. (C) 1998 Elsevier Science Ltd. All rights reserved.

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页码：2227 / 2230

页数：4

相关论文

共 20 条

[1] AN EFFICIENT SYNTHESIS OF 1,2,9,9A-TETRAHYDROCYCLOPROPA[C]BENZ[E]INDOL-4-ONE (CBI) - AN ENHANCED AND SIMPLIFIED ANALOG OF THE CC-1065 AND DUOCARMYCIN ALKYLATION SUBUNITS [J].

BOGER, DL ;

MCKIE, JA .

JOURNAL OF ORGANIC CHEMISTRY, 1995, 60 (05) :1271-1275

[2] CC-1065 and the duocarmycins: Synthetic studies [J].

Boger, DL ;

Boyce, CW ;

Garbaccio, RM ;

Goldberg, JA .

CHEMICAL REVIEWS, 1997, 97 (03) :787-828

[3] SYNTHESIS OF N-(TERT-BUTYLOXYCARBONYL)-CBI, CBI, CBI-CDPI1, AND CBI-CDPI2 - ENHANCED FUNCTIONAL ANALOGS OF CC-1065 INCORPORATING THE 1,2,9,9A-TETRAHYDROCYCLOPROPA[C]BENZ[E]INDOL-4-ONE (CBI) LEFT-HAND SUBUNIT [J].

BOGER, DL ;

ISHIZAKI, T ;

KITOS, PA ;

SUNTORNWAT, O .

JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (23) :5823-5832

[4]

Boger DL, 1997, ISR J CHEM, V37, P119

[5] SYNTHESIS OF N-(PHENYLSULFONYL)-CI, N-((TERT-BUTYLOXY)CARBONYL)-CI, CI-CDPI1, AND CI-CDPI2 - CC-1065 FUNCTIONAL ANALOGS INCORPORATING THE PARENT 1,2,7,7A-TETRAHYDROCYCLOPROP[1,2-C]INDOL-4-ONE (CI) LEFT-HAND SUBUNIT [J].

BOGER, DL ;

WYSOCKI, RJ ;

ISHIZAKI, T .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1990, 112 (13) :5230-5240

[6] Catalysis of the CC-1065 and duocarmycin DNA alkylation reaction: DNA binding induced conformational change in the agent results in activation [J].

Boger, DL ;

Garbaccio, RM .

BIOORGANIC & MEDICINAL CHEMISTRY, 1997, 5 (02) :263-276

[7] Synthesis, chemical properties, and preliminary evaluation of substituted CBI analogs of CC-1065 and the duocarmycins incorporating the 7-cyano-1,2,9,9a-tetrahydrocyclopropa[c]benz[e]indol-4-one alkylation subunit: Hammett quantitation of the magnitude of electronic effects on functional reactivity [J].

Boger, DL ;

Han, NH ;

Tarby, CM ;

Boyce, CW ;

Cai, H ;

Jin, Q ;

Kitos, PA .

JOURNAL OF ORGANIC CHEMISTRY, 1996, 61 (15) :4894-4912

[8] Synthesis and evaluation of CC-1065 and duocarmycin analogues incorporating the iso-CI and iso-CBI alkylation subunits: Impact of relocation of the C-4 carbonyl [J].

Boger, DL ;

Garbaccio, RM ;

Jin, Q .

JOURNAL OF ORGANIC CHEMISTRY, 1997, 62 (25) :8875-8891

[9] Duocarmycin SA shortened, simplified, and extended agents: A systematic examination of the role of the DNA binding subunit [J].

Boger, DL ;

Hertzog, DL ;

Bollinger, B ;

Johnson, DS ;

Cai, H ;

Goldberg, J ;

Turnbull, P .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1997, 119 (21) :4977-4986

[10] AN IMPROVED SYNTHESIS OF 1,2,9,9A-TETRAHYDROCYCLOPROPA[C]BENZ[E]INDOL-4-ONE (CBI) - A SIMPLIFIED ANALOG OF THE CC-1065 ALKYLATION SUBUNIT [J].

BOGER, DL ;

YUN, WY ;

TEEGARDEN, BR .

JOURNAL OF ORGANIC CHEMISTRY, 1992, 57 (10) :2873-2876