3,4-dihydroxy-2-hydroxymethylpyrrolidine from Arachniodes standishii

Furukawa, Yoshihiro; Okuda, S.; Saito, Koshi; Hatanaka, Shin–ichi

doi:10.1016/s0031-9422(00)80773-6

Cited by 71 publications

(31 citation statements)

References 7 publications

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“…[19] Analogously, d-xylose-derived 8,o btained in a few steps from d-xylose, [14d,e] allowed the straightforward synthesis of 1,4-dideoxy-1,4-imino-d-xylitol (9;S cheme 2B), [20,21] an atural product recently found in marine sponges. [22][23][24] The same procedure was applied to 10,r eadily derived from d-ribose, [14e, 25] therebya ffording quantitatively1 ,4-dideoxy-1,4-imino-d-ribitol (11,S cheme2C), [26] an atural compound previously reported to inhibit a-glucosidase and b-mannosidase, [17b, 18, 23] by catalytic hydrogenation. The synthesis of deprotected nitrone 12 in 42 %y ield by BCl 3 debenzylation of the dribo configured 10 was also accomplished (Scheme 2C).…”

Section: Synthesismentioning

confidence: 99%

“…However,t he data do not allow ac lear-cut conclusion concerning the role of the alkyl chain. Indeed,t he best inhibitor (21,I C 50 = 720 nm)h as aC 12 chain at the a-position, whereas the same chain at the nitrogen atom (22)r esulted in an in-crease in IC 50 (4.3 mm). However,i ntroductiono fj ust am ethyl group on the latter resulted in much better inhibition (23, IC 50 = 940 nm).…”

Section: For Pyrrolizidinei Minosugars (Figures 3a Nd 4) Those In Scmentioning

confidence: 99%

“…Gaucher disease (GD)i so ne of the most commona utosomal recessivel ysosomal storage diseases (LSDs) of glycosphingolipids. GD is caused by mutations in GBA (chromosome:1 q21- 22), whiche ncodes the lysosomal enzyme acid b-glucosidase, also knowna sg lucocerebrosidase (GCase;E C3 .2.1.45, MIM*606463). [1] This enzyme hydrolyses the fatty acid glucosylceramide (GlcCer) to ceramide and glucose.…”

Section: Introductionmentioning

confidence: 99%

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Human Acid β‐Glucosidase Inhibition by Carbohydrate Derived Iminosugars: Towards New Pharmacological Chaperones for Gaucher Disease

et al. 2015

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A collection of carbohydrate-derived iminosugars belonging to three structurally diversified sub-classes (polyhydroxylated pyrrolidines, piperidines, and pyrrolizidines) was evaluated for inhibition of human acid β-glucosidase (glucocerebrosidase, GCase), the deficient enzyme in Gaucher disease. The synthesis of several new pyrrolidine analogues substituted at the nitrogen or α-carbon atom with alkyl chains of different lengths suggested an interpretation of the inhibition data and led to the discovery of two new GCase inhibitors at sub-micromolar concentration. In the piperidine iminosugar series, two N-alkylated derivatives were found to rescue the residual GCase activity in N370S/RecNcil mutated human fibroblasts (among which one up to 1.5-fold). This study provides the starting point for the identification of new compounds in the treatment of Gaucher disease.

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Section: Synthesismentioning

confidence: 99%

Section: For Pyrrolizidinei Minosugars (Figures 3a Nd 4) Those In Scmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Human Acid β‐Glucosidase Inhibition by Carbohydrate Derived Iminosugars: Towards New Pharmacological Chaperones for Gaucher Disease

et al. 2015

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“…Polyhydroxylated alkaloids in plants such as castanospermine, DMDP, swainsonine (Colegate et al, 1979), deoxynojirimycin (Yagi et al, 1976), deoxymannojirimycin (Evans et al, 1985a), 2-hydroxymethyl-3,4-dihydroxypyrrolidine (Nash et al, 1985a, Furukawa et al, 1985 and 2-hydroxymethyl-3-hydroxypyrrolidine (Nash et al, 1985b) may be a widespread group of defensive compounds acting as 'digestibility reducing' (Rhoades, 1979) agents. These 'quantitative defences' affect very basic animal functions and therefore are active against an array of herbivores (Fox, 1981).…”

Section: Maculatusmentioning

confidence: 99%

Effects of the plant alkaloid castanospermine as an antimetabolite of storage pests

Nash

Fenton

Gatehouse

et al. 1986

Entomologia Exp Applicata

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The secondary plant compound castanospermine is toxic to the larvae of the bruchid beetle Callosobruchus maculatus E and the flour beetle Tribolium confusum J. & V. when incorporated into the diet. The larval alimentary tract c~-D-glucosidase and i3-D-glucosidase activities of C. maculatus were strongly inhibited by castanospermine in a non-competitive and competitive manner respectively. The larval alimentary tract t3-D-glucosidase activity of T. confusum was strongly inhibited in a competitive manner, but the c~-Dglucosidase activity was not markedly inhibited; however, the 13-D-galactosidase activity exhibited strong uncompetitive inhibition.

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“…Formal removal of one hydroxymethyl group from 246 leads to 1,4-dideoxy-1,4-imino-D-arabinitol (250), which has been found in Arachniodes standishii (FURUKAWA et al 1985) and Angylocalyx botiqueanus . The D-enantiomer 250 was prepared for the first time by FLEET et al from Dxylose (FLEET et al 1985;).…”

Section: C) 14-dideoxy-14-iminopentitolsmentioning

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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3,4-dihydroxy-2-hydroxymethylpyrrolidine from Arachniodes standishii

Cited by 71 publications

References 7 publications

Human Acid β‐Glucosidase Inhibition by Carbohydrate Derived Iminosugars: Towards New Pharmacological Chaperones for Gaucher Disease

Human Acid β‐Glucosidase Inhibition by Carbohydrate Derived Iminosugars: Towards New Pharmacological Chaperones for Gaucher Disease

Effects of the plant alkaloid castanospermine as an antimetabolite of storage pests

Chemistry and Structure-Activity Relationships of Glucosidase Inhibitors

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