Of valiolamine

Horii and Fukase first succeeded in synthesis of (+)-valiolamine (205) by stereoselective chemical conversion of(+)-203 through the key intermediate... 

Lemaire et al. have developed a efficient fructose-1,6-bisphosphate aldolase (FBPA)-mediated synthesis of aminocyclitol analogs of valiolamine [34], This one-pot route involves the formation of two C—C bonds where four stereocenters are created. The first C—C bond formation reaction is catalyzed by the aldolase, coupling DHAP to nitrobutyraldehydes the other one is the result of a highly stereoselective intramolecular Henry reaction occurring on the intermediate nitroketone under acidic conditions during the aldolase-catalyzed reaction and phytase-catalyzed phosphate hydrolysis coupled step (Scheme 4.13). 

Scheme 4.13 Multi-enzyme route for the synthesis of aminocyclitol analogs of valiolamine...

FIGURE 16.7 The commercially available a-glucosidase inhibitors acarbose 5 and voglibose 8, a derivative of valiolamine 7. 

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. 

Fukase, H., and Horii, S., Synthesis of valiolamine and its A-substituted derivatives AO-128, validox-ylamine G, and validamycin G via branched-chain inosose derivatives, J. Org. Chem., 57, 3651, 1992. Morgan, B.P., Holland, D.R., Matthews, B.W., and Bartlett, P.A., Structure-based design of an inhibitor of the zinc peptidase thermolysin, J. Am. Chem. Soc., 116, 3251, 1994. 

T. K. M. Shing and L. H. Wan, Facile synthesis of valiolamine and its diastereomers from (-)-quinic acid. Nucleophilic substitution reactions of 5-hydroxymethyl-cyclohexane-l,2,3,4,5-pentol, J. Org. Chem., 61 (1996) 8468-8479. 

O. Sellier, P. vande Weghe, D. LeNouen, C. Strehler, and J. Eustache, Ring closing metathesis as an efficient approach to branched cyclitols and aminocyclitols A short synthesis of valiolamine, Tetrahedron Lett, 40 (1999) 853-856. 

Shing and Wan have employed quinic acid as starting material for a synthesis of valiolamine 47 and several analogues, 48-50, of this aminocyclitol analogue. 

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]. 

El Blidi, L., Assaf, Z., Bres, F. C., Veschambre, H., Thery, V., Bolte, J., and Lemaire, M., Fructose-l,6-bisphosphate aldolase-mediated synthesis of aminocycUtols (analogues of valiolamine) and their evaluation as glycosidase inhibitors. GhemGatGhem 2009, 1 (4), 463-471. 

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