EFFICIENT DEGRADATION OF FK-506 TO A VERSATILE SYNTHETIC INTERMEDIATE

被引：16

作者：

ASKIN, D

JOE, D

REAMER, RA

VOLANTE, RP

SHINKAI, I

机构：

[1] Department of Process Research, Merck Sharp & Dohme Research Laboratories, Rahway, New Jersey 07065

来源：

JOURNAL OF ORGANIC CHEMISTRY | 1990年 / 55卷 / 20期

关键词：

D O I：

10.1021/jo00307a014

中图分类号：

O62 [有机化学];

学科分类号：

070303 ; 081704 ;

摘要：

An 11-step degradation of natural FK-506 (1) to selectively protected C10-C34 synthetic intermediate 2 has been accomplished in 14% overall yield. The key steps include: (a) lead tetraacetate mediated C9-C10 bond cleavage of 24,32-bis(triisopropylsilyl)-FK-506 (3), (b) simultaneous C10 ester, C22 ketone reduction/C26 oxygen deacylation, and (c) selective bis(triethylsilylation) of the resulting triols 7a, b. The degradate 2 is ready for reacylation at the C26 hydroxyl terminus; hydrolysis of the dimethyl acetal moiety then provides an aldehyde ready for homologation at the C10 terminus. © 1990, American Chemical Society. All rights reserved.

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页码：5451 / 5454

页数：4

相关论文

共 15 条

[1] A MECHANISTIC STUDY OF THE FK-506 TRICARBONYL SYSTEM REARRANGEMENT - SYNTHESIS OF C.9 LABELED FK-506 [J].

ASKIN, D ;

REAMER, RA ;

JOE, D ;

VOLANTE, RP ;

SHINKAI, I .

TETRAHEDRON LETTERS, 1989, 30 (45) :6121-6124

[2] CHEMISTRY OF FK-506 - BENZILIC ACID REARRANGEMENT OF THE TRICARBONYL SYSTEM [J].

ASKIN, D ;

REAMER, RA ;

JONES, TK ;

VOLANTE, RP ;

SHINKAI, I .

TETRAHEDRON LETTERS, 1989, 30 (06) :671-674

[3]

ASKIN D, J ORG CHEM

[4]

COLEMAN RS, 1989, HETEROCYCLES, V28, P157

[5] SYNTHETIC ROUTE TO THE TRICARBONYL REGION OF FK-506 [J].

EGBERTSON, M ;

DANISHEFSKY, SJ .

JOURNAL OF ORGANIC CHEMISTRY, 1989, 54 (01) :11-12

[6] TOTAL SYNTHESIS OF (+/-)-PROSTAGLANDIN D1 - USE OF TRIETHYLSILYL PROTECTING GROUPS [J].

HART, TW ;

METCALFE, DA ;

SCHEINMANN, F .

JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1979, (04) :156-157

[7] A FORMAL SYNTHESIS OF FK-506 - EXPLORATION OF SOME ALTERNATIVES TO MACROLACTAMIZATION [J].

JONES, AB ;

VILLALOBOS, A ;

LINDE, RG ;

DANISHEFSKY, SJ .

JOURNAL OF ORGANIC CHEMISTRY, 1990, 55 (09) :2786-2797

[8] CHEMISTRY OF TRICARBONYL HEMIKETALS AND APPLICATION OF EVANS TECHNOLOGY TO THE TOTAL SYNTHESIS OF THE IMMUNOSUPPRESSANT (-)-FK-506 [J].

JONES, TK ;

REAMER, RA ;

DESMOND, R ;

MILLS, SG .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1990, 112 (08) :2998-3017

[9] TOTAL SYNTHESIS OF THE IMMUNOSUPPRESSANT (-)-FK-506 [J].

JONES, TK ;

MILLS, SG ;

REAMER, RA ;

ASKIN, D ;

DESMOND, R ;

VOLANTE, RP ;

SHINKAI, I .

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1989, 111 (03) :1157-1159

[10] FK-506, A NOVEL IMMUNOSUPPRESSANT ISOLATED FROM A STREPTOMYCES .1. FERMENTATION, ISOLATION, AND PHYSICOCHEMICAL AND BIOLOGICAL CHARACTERISTICS [J].

KINO, T ;

HATANAKA, H ;

HASHIMOTO, M ;

NISHIYAMA, M ;

GOTO, T ;

OKUHARA, M ;

KOHSAKA, M ;

AOKI, H ;

IMANAKA, H .

JOURNAL OF ANTIBIOTICS, 1987, 40 (09) :1249-1255