Inhibition of plant glycosidases by a D-galacturonic acid analog

Tong, Michael K.; Blumenthal, Edward M.; Ganem, Bruce

doi:10.1016/s0040-4039(00)88853-x

Cited by 24 publications

(8 citation statements)

References 5 publications

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“…19 Herein we present a further extension of our aldol-based methodology for the synthesis of the pyrrolidine homoazasugar DGADP and also introduce its applicability for the synthesis of five-membered imino acids of the homoazasugar family. Thus, in this paper we also report novel routes to 2,5-dideoxy-2,5-imino-L-gulonic acid (5) and the previously unknown 2,5-dideoxy-2,5-imino-L-galactonic acid (6).…”

Section: Introductionmentioning

confidence: 56%

“…The residue was dissolved in HCl 1 M (2 mL) and the mixture was heated to 100 • C for 1 h. The reaction mixture was concentrated in vacuo and the residue was diluted with 1% aqueous NH 3 solution and was evaporated again. The residue was purified by ion-exchange chromatography (Dowex 50W-X8, H + form, eluting with 2% aqueous NH 3 solution) followed by reversedphase flash chromatography (RP-18, using H 2,5-Dideoxy-2,5-imino-L-gulonic acid (5). A solution of gulonate 17 (238 mg, 0.77 mmol) in THF (15 mL) and 0.25 M HCl (15 mL, 3.75 mmol) was stirred with 10% Pd/C (24 mg) under H 2 (1 atm) for 12 h at rt.…”

Section: Targeted Pyrrolidine Derivativesmentioning

confidence: 99%

“…1). 5 Both acids can be also considered as 1,5-dideoxy-1,5-imino analogues of glycuronic acids and have been shown to act as competitive inhibitors of b-D-glucuronidases, a-L-iduronidases or galacturonidases. 5,6,7,8 Pyrrolidine imino sugars have also shown promising biological activity.…”

Section: Introductionmentioning

confidence: 99%

“…5 Both acids can be also considered as 1,5-dideoxy-1,5-imino analogues of glycuronic acids and have been shown to act as competitive inhibitors of b-D-glucuronidases, a-L-iduronidases or galacturonidases. 5,6,7,8 Pyrrolidine imino sugars have also shown promising biological activity. Among them, those having a hydroxymethyl group or a polyhydroxylated carbon chain linked to the carbon adjacent to nitrogen, the so-called homoazasugars (aza-C-glycosides), Departamento de Química Fundamental, Facultade de Ciencias, Universidade da Coruña, Campus da Zapateira s/n, 15071 A Coruña, Spain.…”

Section: Introductionmentioning

confidence: 99%

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Synthesis of pyrrolidine homoazasugars and 3,4-dihydroxy-5-hydroxymethylprolines using aldol additions of metalated bislactim ethers to 2,4-O-ethylidene-d-erythroses

et al. 2009

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A strategy for the synthesis of 2,5-dideoxy-2,5-iminohexitols and 2,5-dideoxy-2,5-iminoglyconic acids is described by using diastereoselective aldol additions of metalated bislactim ethers to 2,4-O-ethylidene-d-erythroses and intramolecular N-alkylation as key steps. The nature of the metal fragment of the azaenolate and the beta-alkoxy protecting group for the erythrose moiety were varied to modulate the level and the direction of the asymmetric induction in the aldol addition. The contrasting stereochemical results of the tin(II)-mediated aldol reactions have been rationalized with the aid of density functional theory calculations (B3LYP/cc-pVDZ-PP). DFT calculations indicate that boat-shaped transition structures that allow the formation of a stabilizing hydrogen bond can account for the unusual anti,syn-stereoselectivity of the aldol addition to beta-protected 2,4-O-ethylidene-erythroses. In the addition to the "unprotected" 2,4-O-ethylidene-erythrose, the preference for chair-shaped transition structures in which the erythrose moiety is involved in a six-membered chelate ring is consistent with the experimentally observed syn,anti-stereochemical outcome. The preparative utility of the aldol-based approach was demonstrated by application in concise routes for the synthesis of glycosidase inhibitors 2,5-dideoxy-2,5-iminogalactitol and 2,5-dideoxy-2,5-imino-d-glucitol (DGADP and DGDP) and 3,4-dihydroxy-5-hydroxymethylprolines (2,5-dideoxy-2,5-imino-l-gulonic acid and 2,5-dideoxy-2,5-imino-l-galactonic acid) that may be useful for glycosidase and glycuronidase inhibition.

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Section: Introductionmentioning

confidence: 56%

Section: Targeted Pyrrolidine Derivativesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Synthesis of pyrrolidine homoazasugars and 3,4-dihydroxy-5-hydroxymethylprolines using aldol additions of metalated bislactim ethers to 2,4-O-ethylidene-d-erythroses

et al. 2009

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“…13 This iminoacid has not been isolated from Nature and no biological activity has been assigned to this compound in the literature thus far. Likewise, the D-galacto iminoacid analogue ent-16, (2S,3S,4R,5S)-3,4,5-trihydroxypipecolic acid (2,6dideoxy-2,6-imino-L-galactonic acid), was synthesised by Ganem and co-workers 14 by chemoselective oxidation at C-6 of the corresponding D-galacto-configured iminoalditol. Additionally, a de novo approach 15 to ent-16 starting from building blocks derived from glycine, D-valine and L-tartaric acid was introduced.…”

Section: Introductionmentioning

confidence: 99%

Regioselective intramolecular ring closure of 2-amino-6-bromo-2,6-dideoxyhexono-1,4-lactones to 5- or 6-membered iminuronic acid analogues: synthesis of 1-deoxymannojirimycin and 2,5-dideoxy-2,5-imino-d-glucitol

2008

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1-Deoxymannojirimycin (8c) was synthesised from 2-amino-6-bromo-2,6-dideoxy-D-mannono-1,4-lactone (7) by intramolecular direct displacement of the C-6 bromine employing non-aqueous base treatment followed by reduction of the intermediate methyl ester. Likewise, using aqueous base at pH 12, ring closure took place by 5-exo attack on the 5,6-epoxide leading to 2,5-dideoxy-2,5-imino-L-gulonic acid (9b), which was reduced to 2,5-dideoxy-2,5-imino-D-glucitol (9b). The method was further applied to 2-amino-6-bromo-2,6-dideoxy-D-galacto- as well as D-talo-1,4-lactones (14 and 15). However, only the corresponding six-membered ring 1,5-iminuronic acid mimetics, namely (2R,3R,4S,5R)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-D-galactonic acid, 16) and (2S,3R,4S,5R)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-D-talonic acid, 17), were obtained. The corresponding enantiomers, L-galacto- as well as L-talo-2-amino-6-bromo-2,6-dideoxy-1,4-lactones ent-14 and ent-15, reacted accordingly to give the D-galacto- and L-altro-1,5-iminuronic acid mimetics, (2S,3S,4R,5S)-3,4,5-trihydroxypipecolic acid (2,6-dideoxy-2,6-imino-L-galactonic acid, ent-16) and (2R,3S,4R,5S)-3,4,5-trihydroxypipecolic acids (2,6-dideoxy-2,6-imino-L-talonic acid, ent-17), respectively.

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Mercury(II) Trifluoroacetate

Kočovský¹

2001

Encyclopedia of Reagents for Organic Synthesis

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Inhibition of plant glycosidases by a D-galacturonic acid analog

Cited by 24 publications

References 5 publications

Synthesis of pyrrolidine homoazasugars and 3,4-dihydroxy-5-hydroxymethylprolines using aldol additions of metalated bislactim ethers to 2,4-O-ethylidene-d-erythroses

Synthesis of pyrrolidine homoazasugars and 3,4-dihydroxy-5-hydroxymethylprolines using aldol additions of metalated bislactim ethers to 2,4-O-ethylidene-d-erythroses

Regioselective intramolecular ring closure of 2-amino-6-bromo-2,6-dideoxyhexono-1,4-lactones to 5- or 6-membered iminuronic acid analogues: synthesis of 1-deoxymannojirimycin and 2,5-dideoxy-2,5-imino-d-glucitol

Mercury(II) Trifluoroacetate

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