Semisynthesis of DB-67 and other silatecans from camptothecin by thiol-promoted addition of silyl radicals

被引:41
作者
Du, W
Kaskar, B
Blumbergs, P
Subramanian, PK
Curran, DP [1 ]
机构
[1] Univ Pittsburgh, Dept Chem, Pittsburgh, PA 15260 USA
[2] Ash Stevens Inc, Detroit, MI 48202 USA
关键词
D O I
10.1016/S0968-0896(02)00437-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Thiol- or acid-promoted additions of silyl radicals to camptothecin are reported. At 105 degreesC, mixtures of 7-silyl (favored) and 12-silyl camptothecins are formed alongside substantial amounts of recovered camptothecin. At 160degreesC, 12-silyl isomers are formed preferentially, but the total mass balance is substantially reduced. The silyl radical addition is featured in short semisyntheses of DB-67 (7-tert-butyldimethylsilyl-10-hydroxy camptothecin) from both camptothecin and 10-hydroxycamptothecin. (C) 2002 Elsevier Science Ltd. All rights reserved.
引用
收藏
页码:451 / 458
页数:8
相关论文
共 40 条
[11]   ABSOLUTE RATE CONSTANTS FOR THE ADDITION OF TRIETHYLSILYL RADICALS TO VARIOUS UNSATURATED-COMPOUNDS [J].
CHATGILIALOGLU, C ;
INGOLD, KU ;
SCAIANO, JC .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1983, 105 (10) :3292-3296
[12]  
Curran DP, 2000, ANN NY ACAD SCI, V922, P112
[13]  
Curran DP, 1995, ANGEW CHEM INT EDIT, V34, P2683
[14]   Radical-chain reductive carboxyalkylation of electron-rich alkenes: carbon-carbon bond formation mediated by silanes in the presence of thiols as polarity-reversal catalysts [J].
Dang, HS ;
Kim, KM ;
Roberts, BP .
CHEMICAL COMMUNICATIONS, 1998, (13) :1413-1414
[15]   Conversion of camptothecins to mappicine ketones using silica gel supported sodium hydrogen sulfate catalyst [J].
Das, B ;
Madhusudhan, P .
SYNTHETIC COMMUNICATIONS, 2000, 30 (18) :3321-3325
[16]  
EABORN C, 1967, CHEM COMMUN, P920
[17]   PREPARATION OF MAPPICINE KETONES FROM CAMPTOTHECINS - CHEMISTRY OF THE CAMPTOTHECIN E-RING [J].
FORTUNAK, JMD ;
MASTROCOLA, AR ;
MELLINGER, M ;
WOOD, JL .
TETRAHEDRON LETTERS, 1994, 35 (32) :5763-5764
[18]   Asymmetric total synthesis of (20R)-homocamptothecin, substituted homocamptothecins and homosilatecans [J].
Gabarda, AE ;
Du, W ;
Isarno, T ;
Tangirala, RS ;
Curran, DP .
TETRAHEDRON, 2002, 58 (32) :6329-6341
[19]  
GABARDA AE, 2001, THESIS U PITTSBURGH
[20]   Enantioselective radical-chain hydrosilylation of alkenes using homochiral thiols as polarity-reversal catalysts [J].
Haque, MB ;
Roberts, BP ;
Tocher, DA .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1998, (17) :2881-2889