SYNTHESIS OF THE STAUROSPORINE AGLYCON

被引:72
作者
MOODY, CJ
RAHIMTOOLA, KF
PORTER, B
ROSS, BC
机构
[1] IMPERIAL COLL SCI TECHNOL & MED, DEPT CHEM, LONDON SW7 2AY, ENGLAND
[2] GLAXO GRP RES LTD, WARE SG12 0DP, HERTS, ENGLAND
关键词
D O I
10.1021/jo00033a036
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
A short synthesis of the staurosporine aglycon (6) is reported, the indolocarbazole skeleton being constructed by an intramolecular Diels-Alder reaction followed by a nitrene-mediated ring closure. The synthesis starts by acylation of ethyl indole-2-acetate with oxalyl chloride. The resulting indole-3-glyoxalyl chloride is quenched with 2-nitrocinnamylamine (29) to give the amide (31). Hydrolysis of the ester group and cyclodehydration then gives the pyranoindolone (35). On heating in bromobenzene, the pyranoindolone 35 undergoes intramolecular Diels-Alder reaction to give, after loss of carbon dioxide and air oxidation, the carbazole 36, which on treatment with triethyl phosphite cyclizes to the staurosporine aglycon. The overall yield from ethyl indole-2-acetate is 22.6%.
引用
收藏
页码:2105 / 2114
页数:10
相关论文
共 62 条
[1]   COUPLING OF INDOLEACETIC-ACID TRIANION OR METHYL INDOLEACETIC-ACID DIANION - A BIOMIMETIC APPROACH TO INDOLOCARBAZOLE ALKALOIDS [J].
BERGMAN, J ;
PELCMAN, B .
TETRAHEDRON LETTERS, 1987, 28 (38) :4441-4444
[2]   SYNTHESIS OF INDOLO[2,3-A]PYRROLO[3,4-C]CARBAZOLES BY DOUBLE FISCHER INDOLIZATIONS [J].
BERGMAN, J ;
PELCMAN, B .
JOURNAL OF ORGANIC CHEMISTRY, 1989, 54 (04) :824-828
[3]  
Bergman J., 1988, STUDIES NATURAL PR A, V1, P3
[4]   The rearrangement of thiocyanates into isothiocyanates. [J].
Bergmann, E .
JOURNAL OF THE CHEMICAL SOCIETY, 1935, :1361-1362
[5]  
BUMAGIN NA, 1985, DOKL AKAD NAUK SSSR+, V283, P630
[6]   PRODUCTION AND BIOLOGICAL-ACTIVITY OF REBECCAMYCIN, A NOVEL ANTITUMOR AGENT [J].
BUSH, JA ;
LONG, BH ;
CATINO, JJ ;
BRADNER, WT .
JOURNAL OF ANTIBIOTICS, 1987, 40 (05) :668-678
[7]  
Cadogan J. I. G., 1979, ORGANOPHOSPHORUS REA, P269
[8]  
DAVIS PD, 1990, TETRAHEDRON LETT, V31, P2353
[9]  
DAVIS PD, Patent No. 328026
[10]   X-RAY CRYSTAL-STRUCTURE OF STAUROSPORINE - NEW ALKALOID FROM A STREPTOMYCES STRAIN [J].
FURUSAKI, A ;
HASHIBA, N ;
MATSUMOTO, T ;
HIRANO, A ;
IWAI, Y ;
OMURA, S .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1978, (18) :800-801