Of validamine

Acidic deprotection of 28 gave quantitatively the hydrochloride of (+)-validamine (29), which was chromatographed on Dowex 1X2 (OH-type) with water to yield the free base of 29. Both the hydrochloride and the free base of 29 were identical in all respects with the authentic samples of the natural product... 

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],... 

The majority of naturally occurring aminocarbasugars bears the amino functionality located at the pseudoanomeric position however, replacement of one or more hydroxyl groups by amino functions on the carbasugar backbone may offer great opportunities for structural and stereochemical variation. This section is subdivided into three subsections, dealing with the synthesis of validamine, valiolamine, and valienamine-type carbaglycosyl amine structures. 

A nice stereoselective synthesis of validamine 202 was accomplished by Yoshikawa s group [51], capitalizing on the longstanding familiarity with cyclization of nitrofuranose derivatives [52]. The focal intermediate of the synthesis was nitrofuranose adduct 206 (Scheme 34), which was obtained via a high-yielding multistep transformation of D-glucuronolactone 205. 

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]. 

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-... 

A synthesis of validamine and isomers has been achieved by a stereocontrolled nucleophilic epoxidation of polyhydroxylated cyclohexenyl sulfones obtained from (phoiylsulfonyl)- -oxabicyclo[2.2.1]heptane, itself derived from compound 113. ... 

Among the carba-sugar derivatives, the most important and attractive members are amino carba-sugars, particularly 5a-carba- -D-glucopyran-osylamlne (validamine) and its unsaturated derivative (valienamine). These amino carba-sugars have been synthesized successfully, as well as validamycin antibiotics and some of the aforedescribed enzyme inhibitors. 

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... 

The bromo methyl ester (212) formed by treatment of 30 with hydrogen bromide in acetic acid could also serve as a precursor to validamine. ... 

Validamine (202) and (+)-valienamine ° (203) have been synthesized as the penta-V,0-acetates from the optically active dibromide (51), following essentially the procedure described for the preparation of their racemic modifications. 

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-... 

Novel Synthesis of Natural Pseudo-aminosugars, (+)-Valienamine and (+)-Validamine... 

Now, both the utility and the versatility of our method are demonstrated in the stereoselective synthesis of natural (+)-valienamine (25) and (+)-validamine (29) (7/) (Scheme 3). Furthermore, the anchor effect of an amino group will be described in the stereoselective hydrogenation of the olefin of25 to give 29 (Fig. 1). 

On the final stage to synthesize validamine (29), extensive efforts were directed toward stereoselective hydrogenation of the olefin 24 that would ensure the configuration of the hydroxymethyl group at C-5. 

In summary, the novel synthesis of (+)-valienamine and (+)-validamine has been accomplished by our synthetic strategies for the constructing of carbasugars. The absolutely stereoselective hydrogenation of 26 and 27 to give (+)-validamine (29) is particularly noteworthy. 

Its half-life in soil was less than 4 hours. Microbial degradation of VM-A by Pseudomonas denitrifioans gave rise to D-glucose and validoxylamine A, which was further decomposed into valienamine, validamine and other lower compounds (61). 

After this, an ever-increasing number of carbapyranoses from natural sources was discovered (e.g. validamine, acarbose, gabosines, etc.), whose interesting biological activities were soon ascertained. 

The most popular chemical entries to carbapyranosyl amines of the validamine subgroup exploit two major ouvertures, namely Diels-Alder annulation and ex-chiral pool-derived precursors homologation. 

Treatment of 206 with cesium fluoride in DMF clearly promoted an intramolecular nitro-aldol reaction furnishing, after acetylation, nitrocyclitol 207 as an a, 3-anomeric mixture. Exposure of 207 to liquid ammonia in THF resulted in formation of kinetically favoured a-acetamido derivative 208, probably from a Michael-type addition of ammonia to a nitroolefin intermediate. Reductive elimination of nitro-group in 208 and subsequent deprotection gave validamine 202, in a global 6% yield from glucuronolactone 205. 

Acefia, J.L. et al. A Stereodivergent Access to Naturally Occurring Aminocarbasugars from (Phenylsulfonyl)-7-oxabicy-clo[2.2.1]heptane Derivatives. Total Synthesis of Penta-N.O-acetyl-(i-)-validamine and Its Ci and C2 Stereoisomers. 3.4.1 1994 [101]... 

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