Synthesis of Racemic Carba-sugars

The first three carba-sugars were synthesized by McCasIand and coworkers. Two other carba-sugars were prepared from myoinositol, and the remaining eleven carba-sugars have been synthesized from the Diels-Alder adduct of furan and acrylic acid. Conformational assignments of the carba-sugars were established with the aid of H-n.m.r. spectroscopy. 

The first carba-sugar, 4, was synthesized from the keto acid 13, which was obtained by a two-step reaction from the Diels-Alder adduct (12) of 2-ace-toxyfuran and maleic anhydride. Sodium borohydride reduction of 13, es- 

5a-Carba-/ -DL-gulopyranose (5) was prepared as follows. The Diels-Alder cycloaddition of trans, tra s-l,4-diacetoxy-1,3-butadiene and allyl acetate provided (1,2,5/0)-2,5-diacetoxy-1 -(acetoxymethyl)-3-cyclohexene 

Epimerization of 4 at C-2 provided 5a-carba-a-DL-galactopyranose (6). When the pentaacetate IS was heated in acetic acid containing sulfuric acid, epimerization occurred at C-2 through an intermediary cyclic acetoxonium ion (18), with anchimeric assistance of the vicinal, axial acetoxyl group. After acetylation, 5a-carba-a-DL-galactopyranose pentaacetate (19) was obtained in a yield of 14% it was converted into 6 by hydrolysis. The antimicrobial activity of the racemate 6 was found to be about half that of the natural antibiotic 7 in the same assay system, indicating that the L-antipode is probably inactive.  

From the Diels-Alder Adduct of Furan and Acrylic Acid 

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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. ... 

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. 

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