Total syntheses of de-branched nagstatin and its analogs having glycosidase inhibiting activities

Tatsuta, Kuniaki; Miura, Shota; Ohta, Shigeru; Gunji, Hiroki

doi:10.1016/0040-4039(94)02460-s

Cited by 55 publications

(24 citation statements)

References 7 publications

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“…The hemiacetal function in 2,3,5-tri-O-benzyl-lribofuranose (1) [5] was reduced with sodium borohydride and the resulting free primary hydroxyl function of 2 was selectively protected as the trityl ether 3. Subsequent mesylation of the remaining hydroxyl function provided l-ribitol derivative 4.…”

Section: Resultsmentioning

confidence: 99%

Transformation of Carbohydrate Derived 4‐Azidopentanals Into Highly Functionalized Pyrrolidines Via a Tandem Staudinger/aza‐Wittig/Ugi Multicomponent Reaction

et al. 2006

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Section: Resultsmentioning

confidence: 99%

Transformation of Carbohydrate Derived 4‐Azidopentanals Into Highly Functionalized Pyrrolidines Via a Tandem Staudinger/aza‐Wittig/Ugi Multicomponent Reaction

et al. 2006

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“…Elemental analyses were performed with a PerkinϪElmer 240 C instrument. (1a) was purchased from Aldrich, 3,4-O-isopropylidene--arabinopyranose (1b), [17] 2,3-Oisopropylidene--ribofuranose (1c), [18] 2,3,5-tri-O-benzyl--xylofuranose (1d), [19] 2,3,5-tri-O-benzyl--arabinofuranose (1e), [20] 2,3-Oisopropylidene--erythrose (1f) [21] and (2,3:5,6)-di-O-isopropylidene--mannofuranose (1g) [22] were prepared according to published procedures.…”

Section: Methodsmentioning

confidence: 99%

Preparation of N‐Glycosylhydroxylamines and Their Oxidation to Nitrones for the Enantioselective Synthesis of Isoxazolidines

et al. 2003

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N‐benzyl‐ and N‐methyl‐N‐glycosylhydroxylamines 3a−i were conveniently obtained by reaction of sugars with N‐substituted hydroxylamines according to a novel procedure. Subsequent oxidation occurred at the alkyl group, selectively affording the corresponding C‐phenyl‐ and C‐unsubstituted N‐glycosylnitrones. C‐phenyl‐N‐glycosylnitrones 10 and 13 underwent highly stereoselective 1,3‐dipolar cycloaddition with dimethyl maleate, with the sugar moiety acting as a chiral auxiliary. Final removal of the glycosyl moiety afforded enantiopure enantiomeric isoxazolidines 17 and ent‐17 which are oxa‐analogues of proline diester derivatives. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

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“…C singlets at 133.43 (20) and 134.32 ppm (21), 13 C doublets at 115.09 (20) and 116.70 ppm (21), and strong CO bands at 1736 cm…”

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confidence: 98%

“…We report the synthesis of 14 and 15, their evaluation as inhibitors of the hexosaminidases from bovine kidney (unknown family) and from Jack beans (family 18 [11] [12]), and a comparison of the inhibition to that of the unsubstituted GlcNAcimidazole 16 [2] [13].…”

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confidence: 99%

Synthesis of N‐Acetylglucosamine‐Derived Nagstatin Analogues and Their Evaluation as Glycosidase Inhibitors

Terinek¹,

Vasella²

2005

Helvetica Chimica Acta

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The gluco-configured analogue 15 of nagstatin (1) and the methyl ester 14 were synthesized via condensation of the thionolactams 17 or 18 with the b-amino ester 19. The silyl ethers 20 and 21 resulting from 17 were desilylated to 22 and 23; these alcohols were directly obtained by condensing 18 and 19. The attempted substitution of the C(8)ÀOH group of 22 by azide under Mitsunobu conditions led unexpectedly to the deoxygenated a-azido esters 24. The desired azide 25 was obtained by treating the manno-configured alcohol 23 with diphenyl phosphorazidate. The azide was transformed to the debenzylated acetamido ester 14 that was hydrolyzed to the nagstatin analogue 15. The imidazole-2-acetates 14 and 15 are nanomolar inhibitors of the Nacetyl-b-glucosaminidases from Jack beans and from bovine kidney, submicromolar to micromolar inhibitors of the b-glucosidase from Caldocellum saccharolyticum, and rather weak inhibitors of the snail b-mannosidase. In all cases, the ester was a stronger inhibitor than the corresponding acid. As expected from their glucoconfiguration, both imidazopyridines 14 and 15 are stronger inhibitors of the b-N-acetylglucosaminidase from bovine kidney than nagstatin.Introduction. ± Nagstatin (1), a strong inhibitor of several hexosaminidases [1 ± 4], is a N-acetylgalactosamine-derived tetrahydropyridoimidazole-2-acetic acid [5]. Its inhibitory activity is essentially associated with the imidazole ring and not with the carboxymethyl substituent [2], although substituents on the imidazole ring may strongly affect the inhibition of b (and a-)-glycosidases [6 ± 8]. In the preceding paper [9], we described the influence of the hydrophobic character of C(2)-methyl ester and carboxylic acid substituents on the inhibition of b-glycosidases. Imidazole-2-propionates 10 ± 13 are stronger inhibitors of the b-glucosidase from Caldocellum saccharolyticum and of the b-mannosidase from snail than imidazole-2-acetates 6 ± 9, and these are stronger than imidazole-2-carboxylates 2 ± 5. There is a parallel sequence of inhibitory activity for the methyl esters and the corresponding acids, with the esters being stronger inhibitors.

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Total syntheses of de-branched nagstatin and its analogs having glycosidase inhibiting activities

Cited by 55 publications

References 7 publications

Transformation of Carbohydrate Derived 4‐Azidopentanals Into Highly Functionalized Pyrrolidines Via a Tandem Staudinger/aza‐Wittig/Ugi Multicomponent Reaction

Transformation of Carbohydrate Derived 4‐Azidopentanals Into Highly Functionalized Pyrrolidines Via a Tandem Staudinger/aza‐Wittig/Ugi Multicomponent Reaction

Preparation of N‐Glycosylhydroxylamines and Their Oxidation to Nitrones for the Enantioselective Synthesis of Isoxazolidines

Synthesis of N‐Acetylglucosamine‐Derived Nagstatin Analogues and Their Evaluation as Glycosidase Inhibitors

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