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" Chemistry and biology of novel amino sugars and amino-sugar analogs "
M. A. Szarek
W. A. D. Szarek, W. T.
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Latin Dissertation
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English
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| Record Number
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1113443
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| Doc. No
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TLpq304461825
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| Main Entry
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M. A. Szarek
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W. A. D. Szarek, W. T.
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| Title & Author
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Chemistry and biology of novel amino sugars and amino-sugar analogs\ M. A. SzarekW. A. D. Szarek, W. T.
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| College
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Queen's University (Canada)
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| Date
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1998
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1998
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| Degree
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Ph.D.
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| Page No
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272
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| Abstract
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A synthesis of a series of 2-acetamidopentoses ("2-acetamido-2,4-dideoxy-xylose" derivatives), namely, methyl 2-acetamido-2,4-dideoxy-usd\alphausd- and usd\betausd- sc L-threo-pentopyranosides, methyl 2-acetamido-3-O-acetyl-2,4-dideoxy-usd\alphausd- and usd\betausd- sc L-threo-pentopyranosides, 2-acetamido-2,4-dideoxy- sc L-threo-pentopyranose, and 2-acetamido-1,3-di-O-acetyl-2,4-dideoxy-usd\alpha,\betausd- sc L-threo-pentopyranoses, was achieved from sc D-xylose. The six 2-acetamidopentoses were evaluated for their inhibition of de novo glycoconjugate biosynthesis in female, Swiss White mouse hepatocytes in culture. The synthesis of 1,5,6-trideoxy-6,6-difluoro-1,5-imino- sc D-glucitol (1,6-dideoxy-6,6-difluoronojirimycin) was achieved from sc L-sorbose. The formation of the C-5 difluoromethyl group was accomplished by difluorination of a carbonyl group by DAST. The results of in vitro enzymic evaluation indicate that 1,5,6-trideoxy-6,6-difluoro-1,5-imino- sc D-glucitol is a competitive inhibitor of yeast usd\alphausd-glucosidase (usdK\sb{\rm i}usd = 7.5 mM) and a noncompetitive inhibitor of almond usd\betausd-glucosidase (usdK\sb{\rm i}usd = 8.7 mM). 1,2,5-Trideoxy-1,5-imino- sc D-erythro-pentitol hydrochloride was synthesized from 2-deoxy-ribose. The results of in vitro enzymic evaluation indicate that 1,2,5-trideoxy-1,5-imino- sc D-erythro-pentitol hydrochloride is a potent competitive inhibitor of almond usd\betausd-glucosidase (usdK\sb{\rm i}usd = 35 muM) and a weak competitive inhibitor of A. niger usd\alphausd-galactosidase (usdK\sb{\rm i}usd = 3.8 mM). 1,2,5-Trideoxy-1,5-imino- sc D-threo-pentitol hydrochloride was synthesized from 1,2,5-trideoxy-1,5-imino- sc D-erythro-pentitol hydrochioride or 1,2,5,6-tetrahydropyridine. The results of in vitro enzymic evaluation indicate that 1,2,5-trideoxy-1,5-imino- sc D-threo-pentitol hydrochloride is a weak noncompetitive inhibitor of yeast usd\alphausd-glucosidase (usdK\sb{\rm i}usd = 1.1 mM), and a weak competitive inhibitor of almond usd\betausd-glucosidase (usdK\sb{\rm i}usd = 1.2 mM) and A. niger usd\alphausd-galactosidase (usdK\sb{\rm i}usd = 19.4 mM). The synthesis of 3- ((3R,4S)-3,4-dihydroxy-1-piperidinyl) -1-propanesulfonic acid, sodium salt was achieved by the treatment of 1,2,5-trideoxy-1,5-imino- sc D-erythro-pentitol with 1,3-propane sultone. (4S,5R)-2-(Nitromethyl)-4,5-piperidinediol was synthesized from 5-amino-2,5-dideoxy- sc D-erythro-pentono-1,5-lactam. The results of in vitro enzymic evaluation indicate that (4S,5R)-2-(nitromethyl)-4,5-piperidinediol is a competitive inhibitor of almond usd\betausd-glucosidase (usdK\sb{\rm i}usd = 0.49 mM). Treatment of sodium methyl 5-deoxy-2,3-O-isopropylidene-5-C-sulfonato-usd\betausd- sc D-ribofuranoside and sodium 5-deoxy-2,3-O-isopropylidene-5-C-sulfonato-usd\alphausd- sc D-xylofuranose with Montmorillonite K10 clay in methanol gave anomeric mixtures of methyl glycosides, namely sodium methyl 5-deoxy-5-C-sulfonato-usd\alpha,\betausd- sc D-ribofuranosides and sodium methyl 5-deoxy-5-C-sulfonato-usd\alpha,\betausd- sc D-xylofuranosides. The results of in vitro evaluation of amyloid usd\betausd-peptide aggregation in the presence of each of these two carbohydrate sulfonates indicate that they may inhibit peptide aggregation.
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Acetamidopentoses
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Amino sugars
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Organic chemistry
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Pure sciences
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Trideoxyiminopentitol hydrochloride
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