Of validamycin

Microbial degradation of validamycin A (8) with a cell suspension of Pseudomonas dentrificans afforded validamine (202) and valienamine (203). Hydrogenolysis of validamycin B, followed by acid hydrolysis, yielded hydroxy validamine (204). Valiolamine (205) was isolated and shown to be a component of validamycin G. ° Biosynthesis of these carba-glycosylamines was extensively studied, and the intramolecular aldol addition of the... 

Synthetic studies of validamycins were initially devoted to establishing the structure of validamycin A. The structure in which a ) -D-glucopyranosyl group is attached to 0-3 of the validamine residue was initially proposed on the basis of degradative studies. However, the original structure was re-... 

Total synthesis of (+)-validamycins A and B starting from a common synthetic intermediate was elaborated by the following sequence. Tetra-(9-benzyl-(-l-)-valienamine (370), derived from 211, and the di-O-benzyl derivative (371) of the epoxide were coupled in 2-propanol to produce the protected dicarba compound (374), the structure of which was confirmed by conversion into (-1-)-validoxylamine B nonaacetate. Concurrently, compound 372 was glycosylated and the product oxidized with a peroxy acid, to afford a mixture of products from which the desired epoxide (373) was obtained in 70% yield. Coupling of 370 with 373 in 2-propanol at 120° afforded two carba-trisaccharides, and the major product (47%) was depro-tected and characterized as the dodecaacetate of validamycin B. The pro-... 

Activity of Validamycins and Validoxylamines against Pellicularia sasakii... 

Inhibitory Activity (M) of Validamycin and Validoxylamine against Trehalase... 

Such carba-disaccharides as validoxylamines A and B were synthesized as intermediary compounds in the total synthesis of validamycin antibiotics. Carba-disaccharides related to maltose, isomaltose, cellobiose, the trehaloses, and trehalosamine modifications have also been synthesized. 

The dithiane derivative 60 (Scheme 14) is such a compound, it being made from 2,3 5,6-di-0-isopropylidene-D-mannose by treatment with 2-lithio-l,3-dithiane to give a heptose dithioacetal that was refunctionalized at C-2-C-3 by way of the C-l anion and then converted to the 6,7-epoxide following selective acid-catalyzed cleavage of the 6,7-acetal ring. Treated with n-butyllithium it gives, in 70% yield, the cyclized 61, which is efficiently convertible into validatol 62, a component of validamycin A, by desulfurization with Raney nickel and de-O-protection by use of boron tribromide in dichloromethane [31]. 

Wakae, 0. Matsuura, K. (1975) Characteristics of Validamycin as a Fungicide for Rhizoctonia Disease Control. Review of Plant Protection Research 8, 81-92. 

The first evidence for aminocarbapyranoses occurring in Nature dates back to early 70s with the discovery of validamine 202 (Chart 3), a carbasugar constituent of Validamycins, an antibiotic complex which shows growth inhibition activity against bacterial diseases of rice plants [50]. Shortly after, validamine 202, along with valiolamine 203 and valienamine 204, (Chart 3), were isolated from the fermentation broth of Streptomyces hygroscopicus var. limoneus [50],... 

Dong, H. et al. Biosynthesis of the Validamycins Identification of Intermediates in the Biosynthesis of Validamycin A by Streptomices hygroscopicus var. limoneus. 3.4 2001 [50]... 

The revised structure of validamycin A 85 (compounds 85-02 see pg. 320) was reported by Suami, Ogawa, and Chida [90] in 1980 and it turned to be 4-0-)8-d-glucopyranosyl validamycin A, instead of the 3-O-glucosyl derivative previously reported by Kameda in 1972. 

Total syntheses of (+)-validamycin B (compoimd 367) [199,200], ( + )-valida-mycin A(365) [201,202], validoxylamine B (362) [200], (+)-validoxylamine A(361) and (+)-validamycin E (compoimd 368) [202] have also been reported by the same group. In another report, cleavage of the imino bonds of validoxylamine A derivatives with A-bromosuccinimide was demonstrated. This method reports the preparation of synthetically useful derivatives of (+)-validamine and valienamine [203]. 

Among all the aminocarbasugars obtained by chemical or microbial degradation of validamycins [50], valiolamine is the strongest a-glucosidase inhibitor. Its A-[2-hydroxy-l-(hydroxymethyl)ethyl]-derivative, coded as AO-128, displays higher activity than the parent valiolamine and is undergoing clinical trial for treatment of diabetes [55]. 

SOO tons of validamycin A antibiotic preparations were used in rice cultures. 

Further examples of biochemical modifications of aminoglycosides are enzymatic production of 3-N-carboxymethylribostamycin selective microbial hydrolysis of a- or jS-glucoside linkages of validamycins and synthesis of aminoglyco-side-3 -phosphates The latter compounds have been used as starting materials for the preparation of 3 -deoxyaminoglycosides via the 3 -chloro derivatives. 

The structure of validamycin A (71) was reported by Horii and Kameda. In contrast to the other aminoglycoside antibiotics, all of the... 

The known 7-e carboxylic acid 506, obtained by the condensation of acrylic acid with furan, was used as a substrate for synthesis of validamine, (510) a component of validamycin antibiotics. The treatment of 506 with hydrogen peroxide in formic acid gave the tricyclic compound 507, which after reduction and hydrolysis afforded cyclitol. Treatment of 508 with 2,2-dimethoxy-propane in the presence of an acid gave a mixture of diisopropylidene derivatives in which compound 509 was predominant. Introduction of an amino group, by way of a tosyl ester and azide displacement, followed by hydrogenation and hydrolysis, completed the synthesis of DL-val-... 

C20H35NO13 497.495 Isol. (tom Streptomyces hygroscopicus and Streptomyces prasinus as major component of Validamycin complex. Also obt. on chemical or enzymic hydrol. of Validamycin C, V-2, Validamycin E and Validamycin F. Used in control of fungal infection in rice, potatoes, strawberries and other crops. V. active against Pellicularia sasakii. Amorph. powder. Sol. H2O, MeOH, DMSO, DMF fairly sol. EtOH, Me2CO poorly sol. EtOAc, hexane, Et20. Mp 95° dec Mp 130-135° dec. [a]o +112 (c, 1 in H2O). pAa 6. 

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