Valienamines synthesis

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-... 

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. 

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. 

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. 

In spite of the great biological potential of valienamine and its derivatives, only a few methods have been reported for their synthesis [56]. 

Knapp, S. et al. Intramolecular Amino Delivery Reactions for the Synthesis of Valienamine and Analogues. 3.4.3 1992 [138]... 

The alkylation of a dibenzoate with (phenylsulfonyl)nit-romethane gave an intermediate for the synthesis of (+)-valienamine. ... 

Knapp, S, Naughton, ABJ, Dhar, T G M, Intramolecular amino delivery reactions for the synthesis of valienamine and analogues. Tetrahedron Lett., 33, 1025-1028, 1992. 

The carbocycles substituted at the double bond (with for example, an alkox)methylene group) can also be prepared from the appropriately functionalized unsaturated sugars. Synthesis of a-glucosidase inhibitor—valienamine—was realized from unsaturated sugar chirons as shown in Fig. 9 [86]. 

As shown in O Scheme 44, this method was also applied to total synthesis of (-i-)-valienamine (320) and (+)-validamine (324) [209]. Silyl enol ether 314 derived from D-xylose in nine steps... 

The total synthesis of the trehalose inhibitor salbostatin 451 was achieved by the coupling reaction of the a-valienamine derivative 449 with l,5 2,3-dihydro-D-maimitol (450) imder forcing conditions (sealed tube, 120°C) in a protic solvent [265] (compoimds 449-451),... 

---