Validamycin synthesis

Valence shell electron pair repulsion theory, 1, 564 Valence tautomerism photochromic processes and, 1, 387 y-Valerolactone, o -allyl-a -2-(pyrido[2,3-6]-imidazolyl)-synthesis, 5, 637 Validamycin A as fungicide, 1, 194 Valinomycin... 

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-... 

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. 

Fukase, H., and Horii, S., Synthesis of valiolamine and its A-substituted derivatives AO-128, validox-ylamine G, and validamycin G via branched-chain inosose derivatives, J. Org. Chem., 57, 3651, 1992. Morgan, B.P., Holland, D.R., Matthews, B.W., and Bartlett, P.A., Structure-based design of an inhibitor of the zinc peptidase thermolysin, J. Am. Chem. Soc., 116, 3251, 1994. 

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 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-... 

HI 26 Trehalase and inositol synthesis Glucopyranosyl antibiotics Validamycin Specific for rice sheath blight Rhizoctonia solani)... 

Inhibitors of fungal glucan synthesis are of microbial origin, produced by Strep-tomyces hygroscopicus var. limoneus (HI) and of S. cacaoi var. asoensis (H2) (Table 12.13) [19]. Validamycin is a specific compound for the control of rice sheath blight, whereas polyoxins inhibit a target site that, potentially, is present in all As-comycetes and Basidiomycetes. Nevertheless, the market importance of polyoxins remains limited. 

Ogawa and co-workers have continued to develop syntheses of a large number of racemic branched-chain cyclltols, many related to natural products, from a common original starting material - the Diels-Alder adduct of acrylic acid and furan (see Vol.ll, p.l50 and Vol.13, p.l54). The structure of hydroxyvalidamine, a component of validamycin B, has been confirmed by the synthesis of Its racemic hexaacetate the racemic derivative (43) could be synthesized more efficiently, using the dibromide (44) and the cyclohexene (45) (Scheme 8). Syntheses of racemic valienamine CHgBr CH2OBZ 0—I OAc... 

An intermediate used in the synthesis of (-t-l-validamycin B mentioned in last year s report (see Vol. 21, p. 188) has now been used to prepare (-f)-validoxylamine A, giving a formal total synthesis of validamycin kJ A full paper on the synthesis of (+)-... 

The synthesis of cyclophellitol and analogues as well as Validamycins C, D and F is mentioned in Chapter 19, the coupling of some of the products derived from NBS treatment of Validoxylamine A and trehalostatin can also be found in Chapter 19, the preparation of carbocyciic nucleosides is mentioned in Chapter 20 and the synthesis of oligoglucosyl-inositols in Chapter 4, and the preparation of some highly functionalized cyclopentanes from carbohydrates is covered in Chapter 24. 

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