- Preparation method of high-purity validamine
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Validamine and valienamine are important chemical raw materials but have high separation cost and complex separation process. The invention discloses a preparation method validamine, which includes the steps of: 1) hydrolyzing validoxylamine A through an NBS chemical method by adding the validoxylamine A and NBS to water as a solvent according to certain molar ratio, and performing a reaction for 4 h at 25 DEG C; 2) carrying out adsorption separation to the reaction product through a weak-acidic cation exchange resin, and concentrating the product to obtain a mixture of the validamine and valienamine; 3) under catalysis by a heavy metal catalyst, performing hydrogenation to the mixture, performing adsorption separation to the reaction product through a weak-acidic cation exchange resin, concentrating the product, and vacuum-drying the concentrate to obtain a high-quality validamine sample.
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Paragraph 0020-0022; 0024; 0028; 0032; 0036; 0040; 0044
(2018/01/12)
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- Methods of producing validamycin A analogs and uses thereof
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This disclosure relates to validamycin A biosynthesis and in particular, to methods of producing validamycin A analogs and uses thereof. In a particular example, a method for making a validamycin A analog includes transforming a host cell with one or more recombinant DNA vectors to produce a valN-inactivated mutant; and culturing the valN-inactivated mutant in a culture medium to produce a validamycin A analog, such as 1,1′-bis-valienamine and validienamycin, and their conversion to valienamine. The present disclosure further relates to compositions including such compounds as well as methods of using the compositions, such as for antifungal agents.
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Page/Page column 28
(2012/02/02)
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- Pseudoglycosyltransferase catalyzes nonglycosidic C-N coupling in validamycin a biosynthesis
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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.
- Asamizu, Shumpei,Yang, Jongtae,Almabruk, Khaled H.,Mahmud, Taifo
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experimental part
p. 12124 - 12135
(2011/10/09)
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- METHODS OF PRODUCING VALIDAMYCIN A ANALOGS AND USES THEREOF
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This disclosure relates to validamycin A biosynthesis and in particular, to methods of producing validamycin A analogs and uses thereof. In a particular example, a method for making a validamycin A analog includes transforming a host cell with one or more recombinant DNA vectors to produce a valN-inactivated mutant; and culturing the valN-inactivated mutant in a culture medium to produce a validamycin A analog, such as 1,1′-bis-valienamine and validienamycin, and their conversion to valienamine. The present disclosure further relates to compositions including such compounds as well as methods of using the compositions, such as for antifungal agents.
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- Biosynthesis of the validamycins: Identification of intermediates in the biosynthesis of validamycin A by Streptomyces hygroscopicus var. limoneus
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To study the biosynthesis of the pseudotrisaccharide antibiotic, validamycin A (1), a number of potential precursors of the antibiotic were synthesized in 2H, 3H-, or 13C-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, 2H- or 13C 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 C7 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 [7-3H]validamine ([7-3H]-3) from [7-3H]-12 suggests that 3 may be a pathway intermediate and that the nonincorporation of [7-3H]-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.
- Dong,Mahmud,Tornus,Lee,Floss
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p. 2733 - 2742
(2007/10/03)
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- Synthesis of [7-3H]valienamine, [7-3H]valienone, [7-3H]valiolamine and [7-3H]valiolone from validamycin A
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To investigate the biosynthetic pathway to the cyclitol moieties of acarbose and validamycin A, [7-3H]valienamine, [7-3H]valienone, [7-3H]valiolamine and [7-3H]valiolone were synthesized as plausible precursors. Valienamine together with validamine was isolated from the degradation of validamycin A by Flavobacterium saccharophilum and served as starting material for the synthesis. Validamine was removed partially at the stage of tritylation and completely after the oxidation of the primary hydroxy group at C-7 to the aldehyde. The resulting valienamine aldehyde was reduced with tritiated sodium borohydride to produce [7-3H]valienamine. The latter was converted to [7-3H]valiolamine by a synthetic route described in the literature. The 3H-labeled amines were oxidized to [7-3H]valienone and [7-3H]valiolone, respectively, using 3,5-di-tert-butyl-1,2-bezoquinone (DBQ) followed by hydrolysis with oxalic acid.
- Lee, Sungsook,Tornus, Ingo,Dong, Haijun,Groeger, Stefan
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p. 361 - 372
(2007/10/03)
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- Preparation and biological activity of manno- and galacto-validamines, new 5a-carba-glycosylamines as α-glycosidase inhibitors
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Manno- and galacto-validamines, which are epimers of validamine, were semi-synthesized by the configurational inversion of validamine, a pseudo-sugar analogue of α-D-glucopyranose that has inhibitory activity for α-glucosidases. The inhibitory activities of these analogues were determined against several mannosidases and galactosidases. Manno-validamine shows potent inhibition for the α-mannosidases (competitive, K(i) = 4.6 x 10-5 M for jack beans, and competitive, K(i) = 2.8 x 10-5 M for almonds), and galacto-validamine shows weak inhibition for the α-galactosidases (coffee bean and E. coli). The inhibitory effect of the epimers on the N-linked oligosaccharide-processing mannosidases involved in glycoprotein biosynthesis and lysosomal mannosidase from rat liver were also examined. Mannovalidamine shows potent inhibition on the endoplasmic reticulumal α-mannosidase (competitive, K(i) = 1.2 x 10-6 M), Golgi mannosidases IA, II (competitive, K(i) = 2.8 X 10-5 M), and lysosomal α-mannosidase (competitive, K(i) 1.7 x 10-5 M).
- Kameda, Yukihiko,Kawashima, Kanae,Takeuchi, Masayoshi,Ikeda, Kyoko,Asano, Naoki,Matsui, Katsuhiko
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p. 259 - 264
(2007/10/03)
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- Pseudosugars, 36: Synthesis of methyl 5a′-carbamaltoses linked by imino, ether and sulfide bridges and unsaturated derivatives thereof
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Methyl 5a′-carbamaltoses linked by imino, ether, and sulfide bridges were synthesized by coupling of an amino carbasugar with a sugar epoxide and of the carbasugar epoxide with the oxide anion or thioacetate derived from sugar derivatives. Their unsaturated derivatives related to a potent α-glucosidase inhibitor, methyl acarviosin, were also synthesized. Moderate inhibitory activity against baker's yeast α-glucosidase was observed only for the imino-linked compounds 2 and 5. VCH Verlagsgesellschaft mbH, 1996.
- Tsunoda, Hidetoshi,Sasaki, Shin-Ichi,Furuya, Takashi,Ogawa, Seiichiro
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p. 159 - 165
(2007/10/03)
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- Stereoselective conversion of D-glucuronolactone into pseudosugar: Synthesis of pseudo-α-D-glucopyranose, pseudo-β-D-glucopyranose, and validamine
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Two optically active pseudo-sugars, pseudo-α-D-glucopyranose (12) and pseudo-β-D-glucopyranose (13), were synthesized from D-glucuronolactone in favorable overall yields by using a stereoselective nitromethane addition reaction and a reductive elimination of an ethoxyethoxyl moiety with NaBH4 as key steps. Furthermore, a biologically active pseudo-aminosguar, validamine (18) was efficiently synthesized via a substitution reaction for an acetoxyl group at the β-position of nitro group in a nitrocyclitol derivative (14) which was prepared from a synthetic intermediate (9) of pseudo-d-glucopyranoses (12,13).
- Yoshikawa,Murakami,Yokokawa,Inoue,Kuroda,Kitagawa
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p. 9619 - 9628
(2007/10/02)
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- Syntheses of pseudo-α-D-glucopyranose, pseudo-β-D-glucopyranose, and validamine from D-glucuronolactone
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Using a stereoselective nitromethane addition and a reductive elimination of an ethoxyethoxyl moiety with NaBH4 as key steps, two optically active pseudo-sugars, pseudo-α-D-glucopyranose and pseudo-β-D-glucopyranose, were synthesized from D-glucuronolactone in favorable overall yield. Furthermore, a biologically active pseudo-aminosugar, validamine, was synthesized via a substitution reaction for an acetoxyl group at the β-position of the nitro group in the nitrocyclitol derivative which was prepared from a synthetic intermediate of pseudo-D-glucopyranose.
- Yoshikawa,Murakami,Inoue,Kuroda,Kitagawa
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p. 1197 - 1199
(2007/10/02)
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- SYNTHESES OF VALIDAMINE, EPI-VALIDAMINE, AND VALIENAMINE, THREE OPTICALLY ACTIVE PSEUDO-AMINO-SUGARS, FROM D-GLUCOSE
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Using as a key reaction a Michael-type addition reaction to nitro-olefins or a substitution reaction for an acetoxyl residue at the β-position of the nitro group in pseudo-nitro-sugar, three optically active pseudo-amino-sugars: validamine, epi-validamine, and valienamine, were synthesized from D-glucose.KEYWORDS--pseudo-amino-sugar optically active; validamine; epi-validamine; valienamine; pseudo-amino-sugar synthesis; Michael-type addition, pseudo-nitro-sugar
- Yoshikawa, Masayuki,Cha, Cheon Bae,Okaichi, Yoshihiko,Takinami, Yoshihiko,Yokokawa, Yoshihiro,Kitagawa, Isao
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p. 4236 - 4239
(2007/10/02)
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