32780-32-8Relevant articles and documents
Preparation method of high-purity validamine
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Paragraph 0020-0022; 0024; 0028; 0032; 0036; 0040; 0044, (2018/01/12)
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.
Pseudoglycosyltransferase catalyzes nonglycosidic C-N coupling in validamycin a biosynthesis
Asamizu, Shumpei,Yang, Jongtae,Almabruk, Khaled H.,Mahmud, Taifo
experimental part, p. 12124 - 12135 (2011/10/09)
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.
Biosynthesis of the validamycins: Identification of intermediates in the biosynthesis of validamycin A by Streptomyces hygroscopicus var. limoneus
Dong,Mahmud,Tornus,Lee,Floss
, p. 2733 - 2742 (2007/10/03)
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.