Carba-, synthesis

Synthesis of Carba-maltose, Carba-isomaltose, Carba-cellobiose, and the Like 68... 

VIII. Synthesis of Biologically Active Carba-oligosaccharides. 74... 

The Diels-Alder cycloaddition of furan and acrylic acid, in the presence of hydroquinone as a polymerization inhibitor, provided enrfo-7-oxabicy-clo[2.2.1]hept-5-ene-2-carboxylic acid - (29) in a yield of 45%. Compound 29 was found to be the most accessible and important starting-material for the synthesis of various racemic carba-sugars, as well as their enantiomers. 

Up to the present, fifteen enantiomers have been synthesized among the thirty-two carba-sugars theoretically predicted. Four of them have been prepared from the antipodes of the Diels-Alder adduct 29, two were obtained from quebrachitol, and a chiral synthesis, starting from true sugars, provided the thirteen enantiomers. 

As 29 had been recognized as the most accessible starting-material for the synthesis of racemic carba-sugars, its resolution was successfully achieved with optically active a-methylbenzylamine as chiral reagent. Reaction of 29 with (-l-)-a-methylbenzylamine gave a mixture of two diastereoisomeric salts [(+)-amine, (—)-29 and (+)-amine, (-l-)-29], which were well separated, and the former salt was converted into (—)-29, [a] -111.8° (ethanol). Analogously, (+)-29, [a] +110.7° (ethanol), was obtained. ... 

A facile synthesis of carba- -D-glucopyranose (99) and its l antipode (104) was accomplished by means of resolution of the starting compound DL-( 1,3,5/2,4)-2,3-diacetoxy-4,5-dibromocyclohexane-1 -carboxylic... 

Cyclization of 148 with l,8-diazabicyclo[5.4.0]undec-7-ene (DBU) and a subsequent elimination reaction with acetic anhydride and pyridine furnished compound 149. °- Compound 149 was found to be an important key compound for the following synthesis of carba-sugars of the a-L-altro, fi-D-gluco, P-h-allo, and a-D manno modifications. 

Treatment of 51 with an excess of sodium benzoate in DMF resulted in substitution and elimination, to yield the cyclohexene derivative (228, 36%). The yield was low, but 228 was later shown to be a useful compound for synthesis of carba-oligosaccharides. <9-Deacylation of228 and successive benzylidenation and acetylation gave the alkene 229, which was oxidized with a peroxy acid to give a single epoxide (230) in 60% yield. Treatment of 230 with sodium azide and ammonium chloride in aqueous 2-methoxyeth-anol gave the azide (231,55%) as the major product this was converted into a hydroxyvalidamine derivative in the usual manner. On the other hand, an elimination reaction of the methanesulfonate of 231 with DBU in toluene gave the protected precursor (232, 87%) of 203. 

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-... 

In order to develop potent D-glucosidase inhibitors, a synthesis of carba-disaccharides containing valiolamine (205) was attempted by Horii and his coworkers utilizing method c. Coupling 205 with the 4-ketose 403, using NaBHjCN and hydrochloric acid, was effective in DMF, giving, after deprotection, the epimeric carba-disaccharides (404 and 405). The saturated... 

All sixteen of the racemic carba-sugars predicted are known, as well as fifteen of the enantiomers. The most accessible starting-material for the synthesis of racemic carba-sugars is the Diels-Alder adduct of furan and acrylic acid, namely, e i o7-oxabicyclo[2.2.1]hept-5-ene-2-carboxylicacid (29). Furthermore, adduct 29 is readily resolved into the antipodes, (—)-29 and (+)-29, by use of optically active a-methylbenzylamine as the resolution agent. The antipodes were used for the synthesis of enantiomeric carba-sugars by reactions analogous to those adopted in the preparation of the racemates. 

Among the known enantiomers of carba-sugars, thirteen have been synthesized by a chiral synthesis starting from a true sugar the four modifica-... 

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. 

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