Valienamines

CsHgClO 638-29-9) see Amsacrine Betamethasone divalerate Diflucortolone valerate Irbesartan Valsartan valienamine... 

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... 

Acid hydrolysis of the epoxide (233) obtained from 46 gave, after acetylation, the acetate (234), which, on treatment with DBU, yielded the diene (235), useful for preparation of the azides (237 and 238), the precursors of valienamine analogs. Treatment of 46 with DBU in toluene resulted in... 

Reaction of 47 with NBS in carbon tetrachloride afforded the tribromide (240, 100%). After replacement of the primary bromo group with benzoyl-oxyl, the product (241,47%) was debrominated with zinc dust in ethanol to give the diene (242,64%). Epoxidation of242 produced the isomeric compounds 243 and 244, which were transformed into the azides (245 and 246), convertible into valienamine isomers. ... 

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. 

They also prepared valienamine derivative (+)-227 from the ditosylate (294) derived from 286. The spiro epoxide (295) obtained from 294 was converted into 296 by treatment with selenoxobenzothiazole-tri-... 

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-... 

Among other carba-sugar derivatives, the most important compounds are amino carba-sugars having an amino group at C-1. They are known as validamine, valiolamine, hydroxyvalidamine, and valienamine, and are found in validamycin antibiotics as unique components they have been synthesized in dl forms and also in optically active forms. 

B. M. Trost, L S. Chupak, T. Lubbers Total Synthesis of ( )-and (+)-Valienamine via a Strategy Derived from New Palladium-Catalyzed Reactions , J. Am Chem Soc 1998,120,1732-1740. 

S. Ogawa, M. Ashiura, C. Uchida, S. Watanabe, C. Yamazaki, K. Yamagishi, and J. Inokuchi, Synthesis of potent p-D-glucocerebrosidase inhibitors W-Alkyl-p-valienamines, Bioorg. Med. Chem. Lett., 6 (1996) 929-932. 

Alkene Metathesis in Total Synthesis Valienamine, Agelastatin and Tonantzitlolone... 

Applications to natural product synthesis probe the limits of any synthetic method, as situations arise that would never have been considered in the course of first developing the method. Recent syntheses of valienamine 6, agelastatin 9 and tonantzitlolone 15 pressed the limits of ring-closing metathesis. 

Only blastmycinone (36), valienamine (39), 40, 41, and 44 have no substituent at the branching carbon atom (Type B). A diversity (such as formyl, hydroxymethyl, methyl, 1-hydroxyethyl, acetyl, 2-hydroxyace-tyl, 1,2-dihydroxyethyl, higher alkyl, and carboxyl groups) is observed in the branchings, but, some of them are chemically interconvertible, and also can be derived from a common intermediate (see Scheme 1). 

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). 

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. 

---