Branched-chain sugar nucleosides. III. 9-(3-Deoxy-3-<i>C</i>-methyl-β-<scp>D</scp>-allofuranosyl and ribofuranosyl)adenine

Rosenthal, Alex; Sprinzl, M.

doi:10.1139/v69-657

Cited by 64 publications

(13 citation statements)

References 5 publications

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“…Chromic oxidation (10) of the hydroxyl group at C3 of 1,2:5,6-diisopropylidene-a-D-glucose (11) gave the ketone 3. The Wittig reaction of ketone 3 with ylide prepared from triphenylmethylphosphonium bromide with potassium t-butanolate (12) or with the ylide derived from fluoromethyl triphenylphosphonium tetrafluoroborate (13) with n-butyllithium and potassium t-butanolate (14) gave, after quantitative acid hydrolysis (15) of the acetonides (16,17), the glucose analogs 1 § and 2$ (Scheme 1). Anomers of analogs 1 and 2 were detected in aqueous solutions by NMR spectroscopy.…”

mentioning

confidence: 99%

X-ray analysis of D-xylose isomerase at 1.9 A: native enzyme in complex with substrate and with a mechanism-designed inactivator.

Carrell

Glusker

Burger

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

192

138

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The structures of crystalline D-xylose isomerase (D-xylose ketol-isomerase; EC 5.3.1.5) from Streptomyces rubiginosus and of its complexes with substrate and with an active-site-directed inhibitor have been determined by x-ray diffraction techniques and refined to 1.9-A resolution. This study identifies the active site, as well as two metal-binding sites. The metal ions are important in maintaining the structure of the active-site region and one of them binds C3-O and C5-O of the substrate forming a six-membered ring. This study has revealed a very close contact between histidine and Cl of a substrate, suggesting that this is the active-site base that abstracts a proton from substrate. The mechanism-based inhibitor is a substrate analog and is turned over by the enzyme to give a product that alkylates this same histidine, reinforcing our interpretation. The changes in structure of the native enzyme, the enzyme with bound substrate, and the alkylated enzyme indicate that the mechanism involves an "open-chain" conformation of substrate and that the intermediate in the isomerization reaction is probably a cis-ene diol because the active-site histidine is correctly placed to abstract a proton from C' or C2 of the substrate. A water molecule binds to C'O and C20 of the substrate and so may act as a proton donor or acceptor in the enolization of a ring-opened substrate. We (at the University of Strasbourg, V.B., F.M., D.T., and J.F.B.) designed and synthesized a substrate analog that is a suicide inactivator, analog 2 (Scheme 1) (9). It was used to test whether the D-xylose isomerase studied by x-ray diffraction techniques by us (at the Fox Chase Cancer Center, H.L.C. and J.P.G.) is active in crystalline state. Three crystal structures have been determined and each has been refined: native enzyme, enzyme with bound substrate/product, and MATERIALS AND METHODS Preparation of Active-Site-Directed Inhibitor. 3-Deoxy-C3-methylene-D-glucose (analog 1) and (E)-3-deoxy-C3-fluoromethylene-D-glucose (analog 2) were prepared as follows. Chromic oxidation (10) of the hydroxyl group at C3 of 1,2:5,6-diisopropylidene-a-D-glucose (11) gave the ketone 3. The Wittig reaction of ketone 3 with ylide prepared from triphenylmethylphosphonium bromide with potassium t-butanolate (12) or with the ylide derived from fluoromethyl triphenylphosphonium tetrafluoroborate (13) with n-butyllithium and potassium t-butanolate (14) gave, after quantitative acid hydrolysis (15) of the acetonides (16, 17), the glucose analogs 1 § and 2$ (Scheme 1). Anomers of analogs 1 and 2 were detected in aqueous solutions by NMR spectroscopy.Assay ofXylose Isomerase. The enzyme from S. rubiginosus was assayed by the cysteine-carbazole test (18) as the quantity of D-fructose formed. All reactions were performed in a 0.2 M sodium phosphate buffer (pH 8.0) at 40°C. The reaction mixture (1 ml) contained 0.8 M glucose, 0.01 M tTo whom reprint requests should be addressed. §In a total yield of 80%: m.p. 123-125. 13C-NMR (50 MHz, 2H20) 8 (ppm): 148; 146.4; 98.8; 9...

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confidence: 99%

X-ray analysis of D-xylose isomerase at 1.9 A: native enzyme in complex with substrate and with a mechanism-designed inactivator.

Carrell

Glusker

Burger

et al. 1989

Proc. Natl. Acad. Sci. U.S.A.

192

138

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“…A seqüência desenvolvida parte da 1,2:5,6-Di-O-cicloexilideno-D-glucofuranose 100 66 (Esquema 33), a qual foi submetida às reações sucessivas de oxidação (78%), Wittig (67%) e redução catalítica da dupla resultante (97%), fornecendo o derivado 3-Cmetil-3-deoxi 101. Tratamento de 101 com H 2 SO 4 em MeOH, seguido de mesilação e refluxo com NaI em butanona, conduz à olefina 102 em bons rendimentos.…”

Section: Sínteses Formais Das Crocacinasunclassified

Sínteses totais das crocacinas A, C e D: novos antibióticos isolados de Chondromyces crocatus e Chondromyces pediculatus

Oliveira¹,

Dias²,

Rosso³

2008

Quím. Nova

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“…During the past few years the Wittig reaction has been successfully applied to several 3-keto sugar derivatives to afford unsaturated sugar derivatives; the latter have been readily converted stereoselectively in high yield into the aforementioned type of branched-chain deoxy sugars (4)(5)(6)(7). There is also a report of a light-induced addition of 1,3-dioxolan to an unsaturated carbohydrate in the presence of acetone to afford a branched-chain sugar (8).…”

Section: Introductionmentioning

confidence: 99%

Branched-chain 2-deoxy sugars. V. Application of the Wittig reaction to methyl 3,4-O-isopropylidene-β-D-erythro-pentopyranosid-2-ulose and attempted synthesis of nucleosides of 2-deoxy-2-C-methylpentoses

Rosenthal¹,

Sprinzl²

1970

Can. J. Chem.

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Oxidation of methyl 3,4-0-isopropylidene-p-D-arabinopyranoside (1) with ruthenium tetroxide afforded methyl 3,4-O-isopropylidene-~-~-erythro-pentopyranosid-2-~1lose (2) in 78 % yield. Condensation of methylenetriphenylphosphorane with 2 in the presence of ti-butyllithium yielded methyl 3,4-0-isopropylidene-2-deoxy-2-C-methylene-~-~-eryt1ro-pentopyranoside (3) in 55 % yield. Reduction of the latter with 10% palladium-on-charcoal gave a 7:l mixture of two isomeric 2-deoxy-2-C-methylpentoside derivatives in 95% yield: the preponderant product had the D-I'~/>o configuration. The fully blocked methyl glycosides were de-isopropylidenated with methanolic hydrogen chloride to yield 6 and 7 and these were converted into thep-toluoyl esters (8) and (9). Attempts to utilize the latter in the synthesis of nucleosides of 2-deoxy-2-C-methyl pentoses were unsuccessful.

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Branched-chain sugar nucleosides. III. 9-(3-Deoxy-3-C-methyl-β-D-allofuranosyl and ribofuranosyl)adenine

Cited by 64 publications

References 5 publications

X-ray analysis of D-xylose isomerase at 1.9 A: native enzyme in complex with substrate and with a mechanism-designed inactivator.

X-ray analysis of D-xylose isomerase at 1.9 A: native enzyme in complex with substrate and with a mechanism-designed inactivator.

Sínteses totais das crocacinas A, C e D: novos antibióticos isolados de Chondromyces crocatus e Chondromyces pediculatus

Branched-chain 2-deoxy sugars. V. Application of the Wittig reaction to methyl 3,4-O-isopropylidene-β-D-erythro-pentopyranosid-2-ulose and attempted synthesis of nucleosides of 2-deoxy-2-C-methylpentoses

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