Synthesis of Enantiomeric Carba-sugars

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.  

The absolute configuration of (—)-29 was established by X-ray crystal structure analysis of the bromolactone (89), which was prepared from (—)-29 by bromolactonization with hypobromous acid. It was found that ( )-29 belongs to the d series of carba-sugars, and hence, (+)-29 corresponds to the L series. -  

Starting from (—)-29, carba-a-D-galactopyranose (7) and carba-) -D-glu-copyranose (94) have been synthesized by a reaction analogous to that employed in the preparation of the racemates. -  

Hydroxylactonization of (—)-29 with hydrogen peroxide and formic acid gave the tricyclic compound 90, [a] +47.9° (ethanol). Reduction of 90 with lithium aluminum hydride, followed by acetylation, provided the triacetate 91, which was converted into the pentaacetates 92 and 93 by aceto-lysis. 0-Deacetylation of 92 and 93 gave 7 and 94, respectively The physical constants of all enantiomeric carba-sugars are listed in Table 1. 

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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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