The Experts below are selected from a list of 69 Experts worldwide ranked by ideXlab platform
Taifo Mahmud - One of the best experts on this subject based on the ideXlab platform.
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The VldE and OtsA Reactions.
2013Co-Authors: Michael C. Cavalier, Khaled H. Almabruk, Shumpei Asamizu, Taifo Mahmud, Young-sun Yim, David Neau, Yong-hwan LeeAbstract:The product and substrates of the VldE and OtsA catalyzed reactions are shown. Note the considerable similarity between the ligands of VldE and OtsA, and the conservation of the anomeric centers. The remainders of both biosynthetic pathways are then drawn to completion. VldE catalyzes the formation of validoxylamine A 7′-phosphate via a non-glycosidic C-N bond between GDP-valienol and Validamine 7-phosphate. After the validoxylamine A 7′-phosphate has been produced; VldH and VldK complete the catalytic synthesis of Validamycin A. OtsA catalyzes the formation of trehalose 6-phosphate via a glycosidic bond between UDP-glucose and glucose 6-phosphate. OtsB dephosphorylates trehalose 6-phosphate to produce trehalose.
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Pseudoglycosyltransferase catalyzes nonglycosidic C-N coupling in validamycin a biosynthesis.
Journal of the American Chemical Society, 2011Co-Authors: Shumpei Asamizu, Khaled H. Almabruk, Jongtae Yang, Taifo MahmudAbstract:Glycosyltransferases are ubiquitous in nature. They catalyze a glycosidic bond formation between sugar donors and sugar or nonsugar acceptors to produce oligo/polysaccharides, glycoproteins, glycolipids, glycosylated natural products, and other sugar-containing entities. However, a trehalose 6-phosphate synthase-like protein has been found to catalyze an unprecedented nonglycosidic C–N bond formation in the biosynthesis of the aminocyclitol antibiotic validamycin A. This dedicated ‘pseudoglycosyltransferase’ catalyzes a condensation between GDP-valienol and Validamine 7-phosphate to give validoxylamine A 7′-phosphate with net retention of the ‘anomeric’ configuration of the donor cyclitol in the product. The enzyme operates in sequence with a phosphatase, which dephosphorylates validoxylamine A 7′-phosphate to validoxylamine A.
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genetically engineered production of 1 1 bis valienamine and validienamycin in streptomyces hygroscopicus and their conversion to valienamine
Applied Microbiology and Biotechnology, 2009Co-Authors: Jongtae Yang, Zixin Deng, Linquan Bai, Taifo MahmudAbstract:The antifungal agent validamycin A is an important crop protectant and the source of valienamine, the precursor of the antidiabetic drug voglibose. Inactivation of the valN gene in the validamycin A producer, Streptomyces hygroscopicus subsp. jinggangensis 5008, resulted in a mutant strain that produces new secondary metabolites 1,1′-bis-valienamine and validienamycin. The chemical structures of 1,1′-bis-valienamine and validienamycin were elucidated by 1D and 2D nuclear magnetic resonance (NMR) spectroscopy in conjunction with mass spectrometry and bioconversion employing a glycosyltransferase enzyme, ValG. 1,1′-Bis-valienamine and validienamycin exhibit a moderate antifungal activity against Pellicularia sasakii. Chemical degradation of 1,1′-bis-valienamine using N-bromosuccinimide followed by purification of the products with ion-exchange column chromatography only resulted in valienamine, whereas parallel treatments of validoxylamine A, the aglycon of validamycin A, resulted in an approximately 1:1 mixture of valienamine and Validamine, underscoring the advantage of 1,1′-bis-valienamine over validoxylamine A as a commercial source of valienamine.
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synthesis of 5 epi 6 2 h 2 valiolone and stereospecifically monodeuterated 5 epi valiolones exploring the steric course of 5 epi valiolone dehydratase in validamycin a biosynthesis
Journal of Organic Chemistry, 2001Co-Authors: Taifo Mahmud, Young Ung ChoiAbstract:In validamycin A biosynthesis, as well as that of acarbose, the valienamine and Validamine moieties are ultimately derived from a C(7) sugar, sedoheptulose 7-phosphate, which is cyclized to 2-epi-5-epi-valiolone by a cyclase that operates via a dehydroquinate (DHQ) synthase-like mechanism. 2-epi-5-epi-Valiolone is first epimerized at C-2 to give 5-epi-valiolone and then dehydrated between C-5 and C-6 to yield valienone. To probe the dehydration mechanism of 5-epi-valiolone to valienone, stereospecifically 6alpha- and 6beta-monodeuterated 5-epi-valiolones were synthesized. The key step in the synthesis was desulfurization of the tetrabenzyl-6,6-bis(methylthio)-5-epi-valiolone and introduction of the deuterium utilizing Zn, NiCl(2), ND(4)Cl/D(2)O, and THF. Extensive studies using various combinations of protio- and deuteroreagents and solvents probed the mechanism of the reductive desulfurization, which is crucial for the preparation of stereospecifically monodeuterated 5-epi-valiolones. Incorporation experiments with the labeled precursors in the validamycin A producer strain, Streptomyces hygroscopicus var. limoneus, revealed that the dehydration of 5-epi-valiolone to valienone occurs by a syn elimination of water.
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Biosynthesis of the Validamycins: Identification of Intermediates in the Biosynthesis of Validamycin A by Streptomyces hygroscopicus var. limoneus
Journal of the American Chemical Society, 2001Co-Authors: Haijun Dong, Taifo Mahmud, Ingo Tornus, Sungsook Lee, Heinz G FlossAbstract:To study the biosynthesis of the pseudotrisaccharide antibiotic, validamycin A (1), a number of potential precursors of the antibiotic were synthesized in (2)H-, (3)H-, or (13)C-labeled form and fed to cultures of Streptomyces hygroscopicus var. limoneus. The resulting validamycin A from each of these feeding experiments was isolated, purified and analyzed by liquid scintillation counting, (2)H- or (13)C NMR or selective ion monitoring mass spectrometry (SIM-MS) techniques. The results demonstrate that 2-epi-5-epi-valiolone (9) is specifically incorporated into 1 and labels both cyclitol moieties. This suggests that 9 is the initial cyclization product generated from an open-chain C(7) precursor, D-sedoheptulose 7-phosphate (5), by a DHQ synthase-like cyclization mechanism. A more proximate precursor of 1 is valienone (11), which is also incorporated into both cyclitol moieties. The conversion of 9 into 11 involves first epimerization to 5-epi-valiolone (10), which is efficiently incorporated into 1, followed by dehydration, although a low level of incorporation of 2-epi-valienone (15) is also observed. Reduction of 11 affords validone (12), which is also incorporated specifically into 1, but labels only the reduced cyclitol moiety. The mode of introduction of the nitrogen atom linking the two pseudosaccharide moieties is not clear yet. 7-Tritiated valiolamine (8), valienamine (2), and Validamine (3) were all not incorporated into 1, although each of these amines has been isolated from the fermentation, with 3 being most prevalent. Demonstration of in vivo formation of [7-(3)H]Validamine ([7-(3)H]-3) from [7-(3)H]-12 suggests that 3 may be a pathway intermediate and that the nonincorporation of [7-(3)H]-3 into 1 is due to a lack of cellular uptake. We thus propose that 3, formed by amination of 12, and 11 condense to form a Schiff base, which is reduced to the pseudodisaccharide unit, validoxylamine A (13). Transfer of a D-glucose unit to the 4'-position of 13 then completes the biosynthesis of 1. Other possibilities for the mechanism of formation of the nitrogen bridge between the two pseudosaccharide units are also discussed.
Giovanni Casiraghi - One of the best experts on this subject based on the ideXlab platform.
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variable strategy toward carbasugars and relatives as illustrated by diastereoselective synthesis of 1 deoxy 1 amino pseudo β d gulopyranose alias 1 2 4 tri epi Validamine
Organic Letters, 1999Co-Authors: Gloria Rassu, Luciana Auzzas, Luigi Pinna, Franca Zanardi, Lucia Battistini, Giovanni CasiraghiAbstract:A quick arrival at chiral nonracemic cyclohexanoids is provided, which incorporates useful variability for large product diversity. Central to the construction is the exploitation of the dual nucleophilic character of an easily accessible triad of silyloxy diene synthons derived from the popular five-membered heterocycles furan, pyrrole, and thiophene. To assess the reliability of the procedure, the total synthesis of 1-deoxy-1-amino-pseudo-β-d-gulopyranose (10) (alias 1,2,4-tri-epi-Validamine) is executed, in 12 steps and with a 17% overall yield, by starting with N-tert-butoxycarbonyl-2-[(tert-butyldimethylsilyl)oxy]pyrrole (1) and 2,3-O-isopropylidene-d-glyceraldehyde (2).
Young Ung Choi - One of the best experts on this subject based on the ideXlab platform.
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synthesis of 5 epi 6 2 h 2 valiolone and stereospecifically monodeuterated 5 epi valiolones exploring the steric course of 5 epi valiolone dehydratase in validamycin a biosynthesis
Journal of Organic Chemistry, 2001Co-Authors: Taifo Mahmud, Young Ung ChoiAbstract:In validamycin A biosynthesis, as well as that of acarbose, the valienamine and Validamine moieties are ultimately derived from a C(7) sugar, sedoheptulose 7-phosphate, which is cyclized to 2-epi-5-epi-valiolone by a cyclase that operates via a dehydroquinate (DHQ) synthase-like mechanism. 2-epi-5-epi-Valiolone is first epimerized at C-2 to give 5-epi-valiolone and then dehydrated between C-5 and C-6 to yield valienone. To probe the dehydration mechanism of 5-epi-valiolone to valienone, stereospecifically 6alpha- and 6beta-monodeuterated 5-epi-valiolones were synthesized. The key step in the synthesis was desulfurization of the tetrabenzyl-6,6-bis(methylthio)-5-epi-valiolone and introduction of the deuterium utilizing Zn, NiCl(2), ND(4)Cl/D(2)O, and THF. Extensive studies using various combinations of protio- and deuteroreagents and solvents probed the mechanism of the reductive desulfurization, which is crucial for the preparation of stereospecifically monodeuterated 5-epi-valiolones. Incorporation experiments with the labeled precursors in the validamycin A producer strain, Streptomyces hygroscopicus var. limoneus, revealed that the dehydration of 5-epi-valiolone to valienone occurs by a syn elimination of water.
Xinzhi Chen - One of the best experts on this subject based on the ideXlab platform.
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synthesis of 1 2 3 triazoles from azide derivatised aminocyclitols by catalytic diazo transfer and cuaac click chemistry
European Journal of Organic Chemistry, 2014Co-Authors: Guoquan Zhou, Chao Qian, Xinzhi ChenAbstract:CuII-catalysed diazo transfer and CuI-catalysed azide–alkyne 1,3-dipolar cycloaddition (CuAAC) “click chemistry” were used to synthesis C7N aminocyclitol-derivatised 1,2,3-triazoles. In the course of this work, the -N=N- moiety was transferred onto C7N aminocyclitols such as Validamine, valienamine and valiolamine by employing imidazole-1-sulfonyl azide as the diazo transfer reagent with catalysis by CuII, ZnII and NiII, in moderate to good yields. The obtained azidocyclitols were coupled with various terminal alkynes under modified Meldal's conditions with good to excellent yields. The stereo- and regiochemistry of the products were confirmed by 2D-NMR (NOESY and HMBC). One-pot syntheses of the corresponding 1,2,3-triazoles, as safer and more efficient procedures, were also investigated and gave moderate to good yields.
Gloria Rassu - One of the best experts on this subject based on the ideXlab platform.
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variable strategy toward carbasugars and relatives as illustrated by diastereoselective synthesis of 1 deoxy 1 amino pseudo β d gulopyranose alias 1 2 4 tri epi Validamine
Organic Letters, 1999Co-Authors: Gloria Rassu, Luciana Auzzas, Luigi Pinna, Franca Zanardi, Lucia Battistini, Giovanni CasiraghiAbstract:A quick arrival at chiral nonracemic cyclohexanoids is provided, which incorporates useful variability for large product diversity. Central to the construction is the exploitation of the dual nucleophilic character of an easily accessible triad of silyloxy diene synthons derived from the popular five-membered heterocycles furan, pyrrole, and thiophene. To assess the reliability of the procedure, the total synthesis of 1-deoxy-1-amino-pseudo-β-d-gulopyranose (10) (alias 1,2,4-tri-epi-Validamine) is executed, in 12 steps and with a 17% overall yield, by starting with N-tert-butoxycarbonyl-2-[(tert-butyldimethylsilyl)oxy]pyrrole (1) and 2,3-O-isopropylidene-d-glyceraldehyde (2).
