The preparation of novel homoazasugars and homoazaglycosides and the evaluation of their activity as...

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" The preparation of novel homoazasugars and homoazaglycosides and the evaluation of their activity as glycosidase inhibitors "
O. M. Saavedra Ramallo O. R. Martin

Document Type	:	Latin Dissertation
Language of Document	:	English
Record Number	:	1113372
Doc. No	:	TLpq304481789
Main Entry	:	O. M. Saavedra Ramallo
	:	O. R. Martin
Title & Author	:	The preparation of novel homoazasugars and homoazaglycosides and the evaluation of their activity as glycosidase inhibitors\ O. M. Saavedra RamalloO. R. Martin
College	:	State University of New York at Binghamton
Date	:	1998
student score	:	1998
Degree	:	Ph.D.
Page No	:	180
Abstract	:	vskip225ptusd\betausd-Homonojirimycin 17 and usd\betausd-homogalactostatin 46 were prepared by the highly stereoselective double reductive amination of a 2,6-heptodiulose derivative using amonium formate and usd\rm NaBH\sb3CN.usd The process was unsuccessful with primary amines. Although usd\betausd-Homonojirimycin 17 is a weak inhibitor of usd\alphausd and usd\betausd-glucosidases, it is a good inhibitor of A. Niger amyloglucosidase. usd\betausd-Homogalactostatin 46 inhibits the usd\alphausd-galactosidase present in coffee beans but does not inhibit usd\betausd-galactosidases. The synthesis of N-butyl-usd\betausd-homonojirimycin 70 was achieved by the N-butanoylation of a derivative of 17 followed by reduction to the corresponding tertiary amide. Compound 70 was completely devoid of anti-HIV activity in marked contrast to N-butyl-1-deoxynojirimycin, but it was found however to inhibit the growth of several lines of cancer cells. The coupling of the 1-O-p-toluenesulfonyl derivative of 17, with methyl 2,3,6-tri-O-benzyl-usd\alphausd-D-glucopyranoside, followed by a deprotection step, provided pseudodisaccharide 73, the "homoaza" analog of methyl usd\alphausd-cellobioside and a potential inhibitor of usd\betausd-glucan-processing enzymes. The 1-O-p-toluenesulfonyl derivative 71 provided also access to the 1,N-anhydro derivative of 17, compound 77. Aziridines of this type are potential deactivators of glycosidases. The biological evaluation of compounds 73 and 77 is in progress. 1-Deoxyazaseptanoses 117 and 118 were prepared by internal reductive amination of 7-amino-7-deoxy-2-heptuloses. The outcome of the reductive amination was pH dependent: in the presence of HCl compounds 117 and 118 were the only products of the reaction; in the presence of CH3COOH a third product, the N,O-acetal 116 was also isolated. The ratio of the two azaseptanose derivatives was in both cases near to (117:118) = 1:5. Compound 117 inhibits usdA.\ Niger\ \alphausd-galactosidases and is a weak inhibitor of yeast usd\alphausd-glucosidases. Compound 118 inhibits E. coli usd\betausd-galactosidase and the usd\alphausd-galactosidase present in coffee beans.
Subject	:	Deoxyazaseptanoses
	:	Glycosidase inhibitors
	:	Homoazasugars
	:	Organic chemistry
	:	Pure sciences