Synthesis of 1,3-dideoxy-3-fluoronojirimycin

Lee, C.-Kuan; Jiang, Huixin; Koh, Lip Lin; Xu, Yan

doi:10.1016/0008-6215(93)84229-y

Cited by 12 publications

(1 citation statement)

References 10 publications

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“…Fluoro (OAX et al 1990b;LEE et al 1993;01 et al 1992), acylamino KAPPES and LEGLER 1989), and deoxy derivatives of 1-deoxynojirimycin FLEET et al 1987;JUNGE et al 1989;FLEET and WITTY 1990) can be obtained by such a procedure. Some more recent chemoenzymatic syntheses consist, in principle, of a combination of an enzyme-catalyzed aldol-condensation and a palladium-catalyzed reductive alkylation and lead to deoxynojirimycin derivatives in relatively few steps (ZIEGLER et al 1988;PEDERSON et al 1988; ; KAJlMOTO et al 1991a,b;EFFENBERGER and NULL 1992;LOOK et al 1993;EFFENBERGER et al 1993) (cf.…”

Section: Deoxy Amino and Halogen Derivativesmentioning

confidence: 97%

Chemistry and Structure-Activity Relationships of Glucosidase Inhibitors

Junge¹,

Matzke²,

Stoltefuß³

1996

Oral Antidiabetics

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A. IntroductionWhen intestinal sucrase and pancreatic a-amylase were identified at Bayer as new targets for improved diabetes therapy (PULS et al. 1973), the problem remained of the best way to find a potent and selective inhibitor of these enzymes. The medicinal chemist today has two alternatives in the search for a first lead compound, firstly the screening of thousands of compounds with maximum structural diversity in a random screening approach, or secondly the rational design of a lead compound, when the biochemical mechanism and the structure of the enzyme are weIl known. In the late 1960s, when we started to look for such potent and selective inhibitors, we had to choose the random screening approach, relying mainly on testing of extracts of the culture broths of microorganisms.Today the mechanism of enzymatic splitting of sucrose by intestinal sucrase is fairly weIl understood. First the glucosidic oxygen atom of sucrose is protonated via a carboxyl group of the enzyme. The splitting of the glucosidic C-O bond is further facilitated by the glucosyl cation being stabilized by a second carboxylate group of the enzyme (COGOLI and SEMENZA 1975). FinaIly, the glucosyl cation reacts with water to give the products 0-glucose and o-fructose. The protonated sucrose molecule land the glucosyl cation 11 are two high-energy intermediates of the enzymatic reaction. Today we know that mimics of such high-energy intermediates are often potent inhibitors of the enzyme. Accordingly, compounds similar in structure to o-glucose but with an easily protonated basic N-atom either in the position of the anomeric oxygen atom (inhibitor type I) or in the position of the ring oxygen atom (inhibitor type 11) should be potent inhibitors of sucrase (Fig. 1). Interestingly, both types of inhibitors represented by either acarbose or I-deoxynojirimycin were found in our random screening. In the foIlowing sections these two types of inhibitors are not discussed in a historical order but under structural criteria. Not included in this discussion are the a-amylase inhibitors of protein nature because there is no evidence that they will find any therapeutic application.

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Section: Deoxy Amino and Halogen Derivativesmentioning

confidence: 97%

Chemistry and Structure-Activity Relationships of Glucosidase Inhibitors

Junge¹,

Matzke²,

Stoltefuß³

1996

Oral Antidiabetics

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Synthesis of 5-Azacastanospermine, a Conformationally Restricted Azafagomine Analogue

2001

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The 5-aza-6-deoxy analogue of castanospermine (+/-)-5a and its 1-epimer (+/-)-5b was synthesized. The synthesis started from the known compound 5-benzyloxy-7-hydroxyhepta-1,3-diene, which was protected and subjected to Diels-Alder reaction with 4-phenyl-1,2,4-triazoline-3,5-dione to give two epimeric adducts. One of these was transformed through epoxidation, acetolysis, a series of side-chain transformations that converted it into a terminally protected aldehyde, deprotection, and hydrogenolysis/reductive amination into 5a. By a similar set of reactions the other adduct epimer was converted into 5b. The castanospermine analogue 5a was a weaker inhibitor of almond beta-glucosidase and rice alpha-glucosidase than castanospermine (2) or 1-azafagomine (4), but was considerably more potent than its epimer 5b. This suggests that these enzymes have a strong preference for binding substrates or azasugars with the 6-OH in an axial conformation.

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Imino sugars and glycosyl hydrolases

Stütz

Wrodnigg

2011

Advances in Carbohydrate Chemistry and Biochemistry

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Synthesis of 1,3-dideoxy-3-fluoronojirimycin

Cited by 12 publications

References 10 publications

Chemistry and Structure-Activity Relationships of Glucosidase Inhibitors

Chemistry and Structure-Activity Relationships of Glucosidase Inhibitors

Synthesis of 5-Azacastanospermine, a Conformationally Restricted Azafagomine Analogue

Imino sugars and glycosyl hydrolases

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