SYNTHESIS OF TREHAZOLIN ANALOGS CONTAINING MODIFIED AMINOCYCLITOL MOIETIES

被引:25
作者
UCHIDA, C [1 ]
KITAHASHI, H [1 ]
YAMAGISHI, T [1 ]
IWAISAKI, Y [1 ]
OGAWA, S [1 ]
机构
[1] KEIO UNIV,FAC SCI & TECHNOL,DEPT APPL CHEM,KOHOKU KU,YOKOHAMA,KANAGAWA 223,JAPAN
来源
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1 | 1994年 / 19期
关键词
D O I
10.1039/p19940002775
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
In order to elucidate structure-activity relationships of the trehalase inhibitor trehazolin 1, three analogues: deoxytrehazolin D-2, and de(hydroxymethyl)trehazolin D-3 and its diastereoisomer L-3 were synthesized by coupling of the sugar isothiocyanate 18 with the newly prepared aminocyclopentanetrataols D-10, D-26 and L-26, followed by cyclisation to give the isourea, and deprotection. In addition, an attempt was made to synthesize the analogue 4, the aminocyclitol moiety being replaced with the 5a-carba sugar, validamine. A biological assay showed that enantiomers D-3 and L-3 are strong inhibitors of trehalase, and, interestingly, the latter isomer, having the unnatural-type structure, is similar to 50 times more potent.
引用
收藏
页码:2775 / 2785
页数:11
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