A facile, practical synthesis of 2,6-dideoxy-2,6-imino-7-O-.beta.-D-glucopyranosyl-D-glycero-L-gulo-heptitol (MDL 25,637)

Anzeveno, Peter B.; Creemer, Laura J.; Daniel, John K.; King, Chi Hsin R.; Liu, Paul S.

doi:10.1021/jo00272a015

Cited by 146 publications

(28 citation statements)

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“…Carefully planned extraction procedures have recently uncovered more examples of glycosyl iminosugars isolated from natural sources, thus indicating that their occurrence in Nature is not uncommon. [14] In contrast, few syntheses of glycosyl iminosugars are reported in the literature, [15,16] and they all reflect some difficulties in targeting the final compounds with good yields and selectivities, particularly in the glucosylation step. Interestingly, their inhibitory properties differ substantially from those of the parent iminosugar, with the linked carbohydrate moiety usually generating higher selectivity.…”

Section: Introductionmentioning

confidence: 99%

Total Syntheses of Casuarine and Its 6‐O‐α‐Glucoside: Complementary Inhibition towards Glycoside Hydrolases of the GH31 and GH37 Families

Cardona

Parmeggiani

Faggi

et al. 2009

Chemistry A European J

100

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Total synthesis of naturally occurring casuarine (1) and the first total synthesis of casuarine 6-O-alpha-glucoside (2) were achieved through complete stereoselective nitrone cycloaddition, Tamao-Fleming oxidation and selective alpha-glucosylation as key steps. Biological assays of the two compounds proved their strong and selective inhibitory properties towards glucoamylase NtMGAM and trehalase Tre37A, respectively, which place them among the most powerful inhibitors of these enzymes. The structural determination of the complexes of NtMGAM with 1 and of Tre37A with 2 revealed interesting similarities in the catalytic sites of these two enzymes which belong to different families and clans.

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Section: Introductionmentioning

confidence: 99%

Total Syntheses of Casuarine and Its 6‐O‐α‐Glucoside: Complementary Inhibition towards Glycoside Hydrolases of the GH31 and GH37 Families

Cardona

Parmeggiani

Faggi

et al. 2009

Chemistry A European J

100

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“…The sulfonate/cyanide exchange reaction was also applied to synthesize a-homoiminosugars. [67][68][69] The latter method involving the bisulfite adduct of nojirimicin has the advantage of being applicable to unprotected piperidinose derivatives.…”

Section: Nucleophilic Substitutionmentioning

confidence: 99%

Tactics and strategies for the synthesis of iminosugar C-glycosides: a review

Compain

Chagnault

Martin

2009

Tetrahedron: Asymmetry

160

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“…HOLT et al 1994) (Fig. 43) Other synthetic routes to a-homonojirimycin (156) have been described (Lru 1987;ANZEVENO et al 1989;AOYAGI et al 1990). 156 is also contained in the foliage of Omphalea diandra (KITE et al 1988).…”

Section: Branched and Chain-extended Deoxynojirimycin Derivativesmentioning

confidence: 99%

“…Glycosylation of the aglycon 156 at the 1-hydroxymethyl group leads to MDL 25637 (161) (Lw 1987;ANzEvENo et al 1989) with a clearly lower efficacy in vitro, but a surprisingly good efficacy in vivo (ED50 = 4 mg/kg; sucrose load) (RHINEHART et al 1987a). This may be due to the disaccharidelike structure of 161, which might lead to reduced absorption from the intestine.…”

Section: Ho~sohmentioning

confidence: 99%

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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A facile, practical synthesis of 2,6-dideoxy-2,6-imino-7-O-.beta.-D-glucopyranosyl-D-glycero-L-gulo-heptitol (MDL 25,637)

Cited by 146 publications

References 0 publications

Total Syntheses of Casuarine and Its 6‐O‐α‐Glucoside: Complementary Inhibition towards Glycoside Hydrolases of the GH31 and GH37 Families

Total Syntheses of Casuarine and Its 6‐O‐α‐Glucoside: Complementary Inhibition towards Glycoside Hydrolases of the GH31 and GH37 Families

Tactics and strategies for the synthesis of iminosugar C-glycosides: a review

Chemistry and Structure-Activity Relationships of Glucosidase Inhibitors

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