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.

引用

页码：5451 / 5454

页数：4

共 15 条

[1] A MECHANISTIC STUDY OF THE FK-506 TRICARBONYL SYSTEM REARRANGEMENT - SYNTHESIS OF C.9 LABELED FK-506
ASKIN, D
REAMER, RA
JOE, D
VOLANTE, RP
SHINKAI, I
[J]. TETRAHEDRON LETTERS, 1989, 30 (45) : 6121 - 6124
[2] CHEMISTRY OF FK-506 - BENZILIC ACID REARRANGEMENT OF THE TRICARBONYL SYSTEM
ASKIN, D
REAMER, RA
JONES, TK
VOLANTE, RP
SHINKAI, I
[J]. 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
EGBERTSON, M
DANISHEFSKY, SJ
[J]. JOURNAL OF ORGANIC CHEMISTRY, 1989, 54 (01) : 11 - 12
[6] TOTAL SYNTHESIS OF (+/-)-PROSTAGLANDIN D1 - USE OF TRIETHYLSILYL PROTECTING GROUPS
HART, TW
METCALFE, DA
SCHEINMANN, F
[J]. JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1979, (04) : 156 - 157
[7] A FORMAL SYNTHESIS OF FK-506 - EXPLORATION OF SOME ALTERNATIVES TO MACROLACTAMIZATION
JONES, AB
VILLALOBOS, A
LINDE, RG
DANISHEFSKY, SJ
[J]. 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
JONES, TK
REAMER, RA
DESMOND, R
MILLS, SG
[J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1990, 112 (08) : 2998 - 3017
[9] TOTAL SYNTHESIS OF THE IMMUNOSUPPRESSANT (-)-FK-506
JONES, TK
MILLS, SG
REAMER, RA
ASKIN, D
DESMOND, R
VOLANTE, RP
SHINKAI, I
[J]. 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
KINO, T
HATANAKA, H
HASHIMOTO, M
NISHIYAMA, M
GOTO, T
OKUHARA, M
KOHSAKA, M
AOKI, H
IMANAKA, H
[J]. JOURNAL OF ANTIBIOTICS, 1987, 40 (09) : 1249 - 1255

← 1 2 →