107537-94-0Relevant articles and documents
Total Synthesis of (+)-Galactostatin. An Illustration of the Utility of the Thiazole-Aldehyde Synthesis
Dondoni, Alessandro,Perrone, Daniela
, p. 4749 - 4754 (2007/10/02)
The natural aza sugar (+)-galactostatin (+)-1 has been prepared from D-serine by sequential installation of chiral 1C and 2C units employing thiazole-based reagents.Thus, the D-serine-derived methyl ester 3 was transformed by 2-thiazolyllithium (4) into t
Synthesis of (+)-Galactostatin and (+)-1-Deoxygalactostatin utilizing L-Quebrachitol as a Chiral Building Block
Chida, Noritaka,Tanikawa, Tetsuya,Tobe, Takahiko,Ogawa, Seiichiro
, p. 1247 - 1248 (2007/10/02)
The stereoselective conversion of the naturally occurring optically active cyclitol, L-quebrachitol 1, into galactosidase inhibitors, (+)-galactostatin 2 and (+)-1-deoxygalactostatin 3 is described; the key steps in this synthesis are (i) stereoselective
Amidine, amidrazone, and amidoxime derivatives of monosaccharide aldonolactams: Synthesis and evaluation as glycosidase inhibitors
Papandreou,Tong,Ganem
, p. 11682 - 11690 (2007/10/02)
The synthesis of amidine, amidrazone, and amidoxime derivatives of D-glucono, D-mannono, and D-galactonolactams, which are potent glycosidase inhibitors, is described. With their sugar-like structures and resonance-stabilized, partially positively charged anomeric carbons, these monosaccharide analogs mimic key conformational and electrostatic features of the corresponding glycopyranosyl cations. In the D-gluco series, all three derivatives are potent inhibitors of sweet almond β-glucosidase. Levels of inhibition remain nearly constant despite a 105 change in basicity, indicating that conformational flattening of the hydrolysis intermediate is more important for transition-state binding by the enzyme than charge development. The same D-gluco derivatives also interact with mannose- and galactose-processing enzymes. Considerably weaker inhibition is observed with 1β-amino-1-deoxynojirimycin, which embodies similar endocyclic and exocyclic nitrogens in an undistorted chair conformation. In the D-manno series, the amidrazone and amidoxime are potent inhibitors of jackbean α-mannosidase, mung bean α-mannosidase, fungal β-mannosidase, Golgi α-mannosidase I, α-mannosidase II, and soluble (or endoplasmic reticulum) α-mannosidase. The mannoamidrazone also inhibits Golgi α-mannosidase I and the endoplasmic reticulum mannosidase in vivo. In the D-galacto series, significant inhibition of almond β-glucosidase, bovine liver β-galactosidase, and green coffee bean α-galactosidase is observed, but little or no inhibition of amyloglucosidase.
Stereocontrolled Total Synthesis of Galactostasin from Serine
Dondoni, Alessandro,Merino, Pedro,Perrone, Daniela
, p. 1576 - 1578 (2007/10/02)
An efficient stereoselective total synthesis of (-)-galactostasin (-)-1 from N-tert-butoxycarbonyl-2,3-isopropylidene L-serine methyl ester (21percent overall yield) is described via thiazole intermediates serving as protected aldehydes; the parallel synt
SYNTHESIS OF (+)-GALACTOSTATIN
Aoyagi, Sakae,Fujimaki, Satoshi,Yamazaki, Naoki,Kibayashi, Chihiro
, p. 783 - 787 (2007/10/02)
The chiral synthesis of (+)-galactostatin (3), a new β-galactosidase inhibitor, has been achieved, in which the key step involved a diastereoselective epoxidation of the allylic alcohol (4) derived from L-tartaric acid.
Synthesis of 5-amino-5-deoxy-D-galactopyranose and 1,5-dideoxy-1,5-imino-D-galactitol, and their inhibition of alpha- and beta-D-galactosidases.
Legler,Pohl
, p. 119 - 129 (2007/10/02)
A 12-step route is presented starting from 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose for the preparation of the title compounds and their L-altro analogues. Their synthesis is based on the reduction with Raney nickel of a protected 5-hydroxyimino derivative of L-arabino-hexofuranos-5-ulose, with the following improvements for the preparation of a D-galactofuranose derivative: oxidation at C-3 with pyridinium dichromate-acetic anhydride, stereospecific reduction of a 3-O-acetyl-hex-3-enofuranose intermediate to the D-gulo derivative, and inversion at C-3 of its 3-tosylate with tetrabutylammonium acetate in chlorobenzene. alpha-D-Galactosidase from coffee beans and from Escherichia coli and beta-D-galactosidase from E. coli and Aspergillus wentii were inhibited with Ki values that ranged from 0.0007 to 8.2 microM. Formation of the enzyme-inhibitor complexes with the D-galactose analogue was on the time-scale of minutes, whereas the D-galactitol analogue showed a slow approach to the inhibition only with alpha-D-galactosidase from coffee beans and beta-D-galactosidase from A. wentii. N-Alkylation of the D-galactitol analogue was detrimental to the inhibition except for beta-D-galactosidase from E. coli and beta-D-glucosidase from almonds, but, even with these enzymes, the observed affinity enhancements were 10(2) to 10(3)-times smaller than those of N-alkylated D-galactosylamine and D-glucosylamine.
