Carba sugars

5-Di-0-benzyl-3,4-0-isopropylidene-D-mannitol was ring closed to afford a 9 1 cis/trans mixture of 189 in high yield by (Swern) oxidation and radical cyclization of the dialdehyde using samarium iodide in fcrf-butanol. The cis-diastereoisomer was selectively converted into a cis-cyclic sulfate which underwent cleavage upon treatment with potassium tert-butoxide to afford a cyclo- 

The pseudo-sugars 6a-carha-a- (191) and -p-D-fructopyranose (192) have been prepared in six steps from an enzymatically resolved homochiral cyclohexane-triol building block via a common olefinic intermediate 190 by varying the dihydroxylation strategy (osmium tetroxide vs. m-CPBA respectively). Another non-carbohydrate based route to 5a-carba-sugars has been reported which utilizes a 7-norbornanone-derived cyclohexenoid intermediate. The preparation of carba-a- and -p-galacto-, -a-talo- and -a-fucopyranose derivatives were described.  

In addition to three known gabosines, three new gabosines (L, N and O 201-203 respectively) have been detected as secondary metabolites of Streptomy-ces strains.  

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Scheme 9.33 Synthetic strategy toward carba-sugars, Amaryllidaceae alkaloids, and undecenolides.

CHEMISTRY OF CARBA-SUGARS (PSEUDO-SUGARS) AND THEIR DERIVATIVES... 

There are two forms of carba-sugar carba-pyranoses and -furanoses. The former, especially the carba-hexopyranoses, have been extensively studied during the past two decades, ever since their derivatives were found in Nature as components of important antibiotics. However, very little is known about carba-furanoses, except for 4a-carba-)3-L-arabinofuranose ... 

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. 

In the present article, the preparation of carba-sugars, amino carba-sugars, and biologically active carba-oligosaccharides will be described. 

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-... 

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. 

Substitution reactions of 36 with nucleophilic acetate ions, followed by acetylation, furnished two carba-sugar pentaacetates of the a-DL-ido (38 31 % yield) and a-DL-galacto configurations (19 10%). The reactions seemed to involve formation of an intermediary 2,3-cyclic acetoxonium ion. ... 

Analogous reactions of37 provided two other carba-sugar pentaacetates, of the a-DL-marmo (39 29% yield) and -DL-altro form (40 27%). 

When 35 was heated in acetic acid containing hydrogen bromide, the tribromide 46 was obtained as a single product in 74% yield. Debromina-tion of 46 with zinc dust in acetic acid furnished the cyclohexene derivative 47, which was converted into compound 48 by osmium tetraoxide hydroxyl-ation and acetylation. The substitution reaction of 48 with acetate ions provided carba-a-DL-glucopyranose pentaacetate (49), which gave the carba-sugar 50 on hydrolysis. ... 

There are two possible reaction sites, C-1 and C-4, in the reaction, and two carba-sugars, a-gulo and a-allo, should be obtained, but, during the course of the reaction with prolonged heating, the former carba-sugar is transformed into the latter by epimerization by way of 3,4-cyclic acetoxonium ions. ... 

The last then-unknown carba-sugar, carba-) -DL-talopyranose pentaacetate (83), was synthesized from 36 as follows. Epoxidation of 36 with sodium methoxide gave, at the early stage of the reaction, the 2,3-epoxide... 

At>-7-Oxabicyclo[2.2.l]hept-5-ene-2-carboxylic acid - (84) was isolated as a minor component from the mother liquor of 29. Compound 84 is an epimer of 29 at C-2, and three known carba-sugar pentaacetates have been prepared from 84 as follows. 

Now, all sixteen of the predicted racemic carba-sugars have been synthesized, and their physical constants are listed in Table I. 

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. - ... 

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. 

From L-arabinose, carba-sugars of the a-D-gluco and h-altro types were prepared from D-arabinose, carba-a-L-mannopyranose from D-ribose, that of the fi-L-manno modification from D-xylose, those of the -L-gluco and a-D-altro forms and, from D-glucose, those of the P-L-allo a-L-... 

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