Asymmetric total synthesis of (20R)-homocamptothecin, substituted homocamptothecins and homosilatecans

被引：29

作者：

Gabarda, AE ^{[1
]}

Du, W ^{[1
]}

Isarno, T ^{[1
]}

Tangirala, RS ^{[1
]}

Curran, DP ^{[1
]}

机构：

[1] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA

来源：

TETRAHEDRON | 2002年 / 58卷 / 32期

基金：

美国国家卫生研究院;

关键词：

homosilatecans; topoisomerase; antitumor;

D O I：

10.1016/S0040-4020(02)00632-4

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

An efficient asymmetric synthesis of a key DE lactone pyridone intermediate in the synthesis of homocamptothecin is reported. The synthesis is scalable and features a Stille coupling and a Sharpless asymmetric epoxidation as the key steps. The key intermediate has been parleyed into homocamptothecin and an assortment of fluorinated homocamptothecins and homosilatecans (7-silylhomocamptothecins), thereby providing the first asymmetric entry to this important new class of antitumor agents. (C) 2002 Published by Elsevier Science Ltd.

引用

收藏

页码：6329 / 6341

页数：13

相关论文

共 40 条

[1] Homocamptothecin, an E-ring-modified camptothecin analogue, generates new topoisomerase I-mediated DNA breaks [J].

Bailly, C ;

Lansiaux, A ;

Dassonneville, L ;

Demarquay, D ;

Coulomb, H ;

Huchet, M ;

Lavergne, O ;

Bigg, DCH .

BIOCHEMISTRY, 1999, 38 (47) :15556-15563

[2]

Bérillon L, 1998, SYNLETT, P1359

[3] Novel A,B,E-ring-modified camptothecins displaying high lipophilicity and markedly improved human blood stabilities [J].

Bom, D ;

Curran, DP ;

Chavan, AJ ;

Kruszewski, S ;

Zimmer, SG ;

Fraley, KA ;

Burke, TG .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (16) :3018-3022

[4] The novel silatecan 7-tert-butyldimethylsilyl-10-hydroxycamptothecin displays high lipophilicity, improved human blood stability, and potent anticancer activity [J].

Bom, D ;

Curran, DP ;

Kruszewski, S ;

Zimmer, SG ;

Strode, JT ;

Kohlhagen, G ;

Du, W ;

Chavan, AJ ;

Fraley, KA ;

Bingcang, AL ;

Latus, LJ ;

Pommier, Y ;

Burke, TG .

JOURNAL OF MEDICINAL CHEMISTRY, 2000, 43 (21) :3970-3980

[5]

Boymond L, 1998, ANGEW CHEM INT EDIT, V37, P1701, DOI 10.1002/(SICI)1521-3773(19980703)37:12<1701::AID-ANIE1701>3.0.CO

[6]

2-U

[7] Chemistry of the camptothecins in the bloodstream - Drug stabilization and optimization of activity [J].

Burke, TG .

CAMPTOTHECINS: FROM DISCOVERY TO THE PATIENT, 1996, 803 :29-31

[8] A practical six-step synthesis of (S)-camptothecin [J].

Comins, DL ;

Nolan, JM .

ORGANIC LETTERS, 2001, 3 (26) :4255-4257

[9] A 6-STEP SYNTHESIS OF (+/-)-CAMPTOTHECIN [J].

COMINS, DL ;

HONG, H ;

SAHA, JK ;

GAO, JH .

JOURNAL OF ORGANIC CHEMISTRY, 1994, 59 (18) :5120-5121

[10] ASYMMETRIC-SYNTHESIS OF CAMPTOTHECIN ALKALOIDS - A 9-STEP SYNTHESIS OF (S)-CAMPTOTHECIN [J].

COMINS, DL ;

HONG, H ;

JIANHUA, G .

TETRAHEDRON LETTERS, 1994, 35 (30) :5331-5334

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