Aminocyclitol inhibitors

S. Ogawa, C. Uchida, and Y. Yuming, Synthesis of aminocyclitol moieties of trehalase inhibitors, trehalostatin and trehazolin, J. Chem. Soc. Chem. Commun. (1992) 886-888. 

Nakata, M, Akazawa, S, Kitamura, S, Tatsuta, K, Enantiospecific total synthesis of (—)allosazoline, an aminocyclitol moiety of the insect chitinase inhibitor allosamidin. Tetrahedron Lett., 32, 5363-5366, 1991. 

Valiolamine (89), an aminocyclitol produced by Streptomyces hygroscopicus var. limoneus, is a potent inhibitor of pig intestinal maltase and sucrase, with IC50 values of 2.2 and 0.049 pM, respectively [107]. Numerous iV-substituted valiolamine derivatives were synthesized to enhance its a-glucosidase inhibitory activity in vitro and the very simple derivative voglibose (90), which is obtained by reductive amination of valiolamine with dihydroxyacetone, was selected as the potential oral antidiabetic agent [108]. Its IC50 values toward maltase and sucrase were 0.015 and 0.0046 pM, respectively. Voglibose (the brand name Basen) has been commercially available for the treatment of type 2 diabetes in Japan since 1994. 

Asano et al. [205] used a combination of enzymatic and chemical reactions to synthesize eight possible mono-j8-D-glucosides of validoxylamine A. In another synthesis by Ogawa and coworkers [206], treatment of validoxylamine A or its per-O-benzylated derivative with NBS under different conditions resulted in the formation of mixtures of keto- and aminocyclitol derivatives (e.g., 369 and 370). These compounds were used to prepare the dimeric aminocyclitol 371, which is a potent trehalose inhibitor (compounds 369-371). 

An impressive number of papers has appeared in the past few years based on the use of sugar thioureas as intermediates in the synthesis of the naturally occurring potent trehalase inhibitor trehazolin (251) and of several isomers.52 396-404 The key reaction step involved the cyclization of an A,iV-disubstituted a-D-glucopyranosyl-aminocyclitol (a-D-glucopyranosyl-... 

The aminocyclitols allosamizoline (266) and demelhylallosamizoline (267), which are found in the pseudotrisaccharide chitanase inhibitors known as allosamidin and demethylallosamidin, have been prepared from cyclic thiocarbamate411 (264) and /1-hydroxy thiourea412 (265) precursors,... 

The branched aminocyclitol valiolamine (a pseudoamino sugar, C7H15NO5, Mr 193.20) from Streptomyces hygmscopicus subsp. limoneus is also a strong a-glucosidase inhibitor. 

C19H33NO14 499.468 Aminocyclitol antibiotic. Prod, by Strep-tomyces cahus and other Streptomyces spp. Active against gram-positive and -negative bacteria and phytopatho-genic fungi. a-Amylase inhibitor. Powder -i- 2H2O. 

Aminocyclitol antibiotic. Prod, by Strep-tomyces hygroscopicus ssp. limoneus. Also formed by degradn. of Validamy-cins by soil bacteria. a-Glucosidase inhibitor useful for treating hypoglycemia. Active against some Bacillus sp. Powder. Sol. H2O. 

L. El Blidi, M. Ahbala, 1. Bolte, M. Lemaire, Straightforward chemo-enzymatic synthesis of new aminocyclitols, analogues of valiolamine and their evaluation as glycosidase inhibitors. Tetrahedron Asymmetry 17 (2006) 2684-2688. 

The aminocyclitol synthesis mediated by DHAP-dependent aldolases consists of a double aldol reaction, the first one enzymatically controlled by aldolases and the second one a spontaneous intramolecular nitro-aldol reaction (i.e., the Henry reaction) (Scheme 10.18). The latter makes use of the electrophilic carbonyl unit introduced by the first aldol addition on the nucleophilic character of carbon bonded to a nitro group installed from the acceptor (e.g., 62). This twofold C—C bond-forming reaction cascade was shown to deliver, after nitro group reduction, aminocyclitol analogs of valiolamine (63), of interest as inhibitors of intestinal glycosidases [141]. 

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