37248-47-8Relevant articles and documents
Catalytic analysis of the validamycin glycosyltransferase (ValG) and enzymatic production of 4″-epi-validamycin A
Xu, Hui,Minagawa, Kazuyuki,Bai, Linquan,Deng, Zixin,Mahmud, Taifo
experimental part, p. 1233 - 1236 (2009/11/30)
ValG is a glycosyltransferase (GT) that is responsible for the glucosylation of validoxylamine A to validamycin A. To explore the potential utilization of ValG as a tool for the production of validamycin analogues, a number of nucleotidyldiphosphate-sugars were evaluated as alternative substrates for VaIG. The results indicated that in addition to its natural substrate, UDP-glucose, ValG also efficiently utilized UDP-galactose as sugar donor and resulted in the production of an unnatural compound, 4″-epi-validamycin A. The new compound demonstrated a moderate growth inhibitory activity against the plant fungal pathogen Rhizoctonia solani (=Pellicularia sasakii). A comparative analysis of ValG with its homologous proteins revealed that ValG contains an unusual DTG motif, in place of the DXD motif proposed for metal ion binding and/or NDP-sugar binding and commonly found in other glycosyltransferases. Site-directed mutagenesis of the DTG motif of ValG to DCD altered its preferences for metal ion binding, but did not seem to affect its substrate specificity.
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.
Synthetic studies on antibiotic validamycins. Part 13. Total synthesis of (+)-validamycins A and E, and related compounds
Miyamoto, Yasunobu,Ogawa, Seiichiro
, p. 1013 - 1018 (2007/10/02)
(+)-Validoxylamine A (1) has been completely synthesized by deoxygenation of the validoxylamine B derivative (6) through formation of the aziridine, nucleophilic displacement with toluenethiol, reduction with Raney nickel, and deprotection. The validoxylamine A derivative (10) obtained was convertible, by glycosylation followed by deprotection, into validamycins A (2), E (3), and their analogues, which constitutes a total synthesis thereof.
Synthetic Studies on Antibiotic Validamycins. Part 11. Synthesis of Validamycin A
Ogawa, Seiichiro,Nose, Taisuke,Ogawa, Takao,Toyokuni, Tatsushi,Iwasawa, Yoshikazu,Suami, Tetsuo
, p. 2369 - 2374 (2007/10/02)
The antibiotic validamycin A (1a) has been synthesized for the first time (as its undeca-O-acetate) by glycosylation of the partially protected derivative (8) of the aglycone, validoxylamine A (2a), with 2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl chloride (11), followed by deprotection, thereby establishing the structure previously assigned.The totally O-acetylated derivative (19) of 7-deoxyvalidamycin A has been synthesized in a similar fashion.
A FORMAL TOTAL SYNTHESIS OF VALIDAMYCIN A
Ogawa, Seiichiro,Ogawa, Takao,Nose, Taisuke,Toyokuni, Tatsushi,Iwasawa, Yoshikazu,et al.
, p. 921 - 922 (2007/10/02)
Validamycin A has been prepared by a glycosidation of the partly blocked validoxylamine A, followed by deprotection.Since a racemic form of validoxylamine A has been totally synthesized, the synthesis of validamycin A is achieved by the present study.
A TOTAL SYNTHESIS OF 6"-EPIVALIDAMYCIN A AND ITS DIASTEREOMER
Ogawa, Seiichiro,Inoue, Makoto,Iwasawa, Yoshikazu
, p. 1085 - 1088 (2007/10/02)
A total synthesis of the 6"-epimer of validamycin A and its diastereomer has been accomplished by a coupling reaction of the racemic peracyl 5,6-dihydroxy-1-hydroxymethyl-1,3-cyclohexadiene monoepoxide, the precursor of the unsaturated branched-chain cyclitol portion, with the protected β-D-glucopyranosylvalidamine, followed by acid hydrolysis and O-deacylation.
