عنوان

Chemistry and biology of novel amino sugars and amino-sugar analogs

Number

TLpq304461825

.Language of Text, Soundtrack etc

انگلیسی

Title Proper

Chemistry and biology of novel amino sugars and amino-sugar analogs

General Material Designation

[Thesis]

First Statement of Responsibility

M. A. Szarek

Subsequent Statement of Responsibility

W. A. D. Szarek, W. T.

Name of Publisher, Distributor, etc.

Queen's University (Canada)

Date of Publication, Distribution, etc.

1998

Specific Material Designation and Extent of Item

272

Dissertation or thesis details and type of degree

Ph.D.

Body granting the degree

Queen's University (Canada)

Text preceding or following the note

1998

Text of Note

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.

Acetamidopentoses

Amino sugars

Organic chemistry

Pure sciences

Trideoxyiminopentitol hydrochloride

M. A. Szarek

W. A. D. Szarek, W. T.

Electronic name

p

[Thesis]

276903

a

Y