37248-47-8 Usage
Description
Validamycin A is a potent antifungal agent and a member of the class of validamycins. It is produced by the fermentation of Streptomyces hygroscopicus var. limoneus nov. var (30) and is a colorless, odorless, hygroscopic powder. Validamycin A is characterized by its negligible vapor pressure at room temperature and its solubility in various solvents, such as water, methanol, dimethylformamide, and dimethyl sulfoxide. It is also slightly soluble in ethanol and acetone, and sparingly soluble in diethyl ether and ethyl acetate. Validamycin A is commonly regarded as an aminoglycoside, but it shares little in common with conventional aminoglycosides such as streptomycin and gentamicin.
Uses
Used in Crop Production:
Validamycin A is used as an antibiotic fungicide for the control of fungi in crop production. It acts as a potent inhibitor of trehalase, an important enzyme in carbohydrate storage and utilization in fungi.
Used in Control of Rhizoctonia Diseases:
Validamycin A is used as a fungicide for the control of Rhizoctonia diseases in various crops, including rice (sheath blight), potatoes, vegetables, strawberries, tobacco, and other crops.
Used in Pharmaceutical Industry:
Although not explicitly mentioned in the provided materials, due to its potent antifungal properties and unique structure, Validamycin A could potentially be used in the pharmaceutical industry for the development of new antifungal drugs or as a component in drug delivery systems targeting fungal infections.
Pharmacology
Validamycin A specifically inhibits trehalase in R. solani
AG-1 in a competitive manner between validoxylamine A (the possible active form of validamycin A) and the
substrate, trehalose (33). Because trehalose is a storage
carbohydrate in some fungi, trehalase is suggested to play
an essential role for the digestion of trehalose to D-glucose
and for its transportation to the hyphal tips (34).
Metabolic pathway
Validamycin A is an effective fungistatic (as opposed to fungicidal)
antibiotic which has a very low toxicity to mammals and fish. This is
presumably a consequence of its selective mode of action, the inhibition of
trehalase. It is readily degraded under environmental conditions.
Degradation
Validamycin A is stable at room temperature in neutral or alkaline media
but is unstable in acidic media.
Toxicity evaluation
Acute
oral LD50 for rats and mice >20 g/kg. Acute percutaneous
LD50 for rats >5 g/kg. Nonirritating to skin (rabbits).
Not a skin sensitiser (guinea pigs). Inhalation LC50 (4 h)
for rats >5 mg/L air. NOEL: In 90-d feeding trials, rats
receiving 1 g/kg of diet and mice receiving 2 g/kg of diet
showed no ill-effects. In 2-y feeding trials, NOEL for rats
was 40.4 mg/kg daily. Toxicity Class WHO (a.i.) III; EPA
(formulation) IV.
Check Digit Verification of cas no
The CAS Registry Mumber 37248-47-8 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 3,7,2,4 and 8 respectively; the second part has 2 digits, 4 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 37248-47:
(7*3)+(6*7)+(5*2)+(4*4)+(3*8)+(2*4)+(1*7)=128
128 % 10 = 8
So 37248-47-8 is a valid CAS Registry Number.
InChI:InChI=1/C20H35NO13/c22-3-6-1-8(12(26)15(29)11(6)25)21-9-2-7(4-23)19(17(31)13(9)27)34-20-18(32)16(30)14(28)10(5-24)33-20/h1,7-32H,2-5H2
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.
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.
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.