Acyclic sugar derivatives

The synthesis shown in Fig. 40 provided access to heptoses,55 but according to our definition, this is not a higher sugar synthesis. However, the approach to such derivative was based on the Baylis-Hillman reaction of acyclic sugar-derived aldehydes, a reaction not commonly applied in sugar chemistry and worth to mention in this review. 

The conformations in solution of various acylated l,l-bis(acyl-amido)-l-deoxypentitols have been examined by p.m.r. spectroscopy.793 In line with general behavior observed78 with other acyclic-sugar derivatives, it was found that the arabino and lyxo derivatives adopt extended, zigzag conformations, whereas the ribo and xylo derivatives favor sickle conformations that result by rotation about one carbon-carbon bond of the backbone chain to alleviate a destabilizing 1,3-interaction of acyloxy substituents that would be present in the extended, zigzag conformation. 

Conformational Equilibria of Acylated Aldopentopyranose Derivatives and Favored Conformations of Acyclic Sugar Derivatives... 

T1he conformational studies (I) on acyclic sugar derivatives and on aldopentopyranose derivatives that have been conducted in our laboratories during the last few years are surveyed, and some of our more recent results in each of these areas are introduced. For each aspect the sugar derivatives were examined in solution by proton magnetic resonance (PMR) spectroscopy, and the data obtained were used to provide conformational information. Acyclic systems will be treated first. 

Closely similar results were obtained with various diphenyl dithioacetal acetates (7), with the unsubstituted diethyl dithioacetals (8), and with the aldehydo-pentose peracetates (9) and the tetra-O-acetylaldo-pentose dimethyl acetals (10). Subsequent work in other laboratories has shown the same general principles for the methyl 5-hexulosonates (11) and the pentononitrile tetraacetates (12), two examples where a full series of stereoisomers has been studied. Other workers have investigated isolated examples or partial series (13, 14, 15, 16, 17, 18), and parallel work by x-ray crystallography (19, 20, 21, 22) on acyclic sugar derivatives in the solid state has shown excellent correlation with the general principles outlined here for the molecules in solution. 

These results suggest that in the pentitols and hexitols, at least, the intermolecular H-bonds have only a secondary influence on the shape of the molecules in the solid state. The observed conformations in the solid state can be rationalized (16) in terms of the intramolecular interactions between hydroxyls which are believed to involve energies of the order of several kilocalories (27) (the interpretation of the NMR spectra of acetylated acyclic sugar derivatives in solution is based on the same type of hypothesis (29)). 

As a result of these considerations, a rejuvenescence of interest in sulfonic esters of acyclic-sugar derivatives, e.g., of sugar mercaptals, is to be expected, since they afford a route to the synthesis not only of compounds having one or more methylene groups at desired positions in the sugar chain (of which 2-deoxy-D- ribose, or 2-deoxy-D-eryother groupings, e.g., double bonds, at selected positions in the chain. 

The reactions of Grignard reagents with acyclic sugar derivatives have also been investigated as potential routes for the synthesis of compounds containing asymmetric, benzylic carbon atoms.22 W. A. 

SCHEME 10.33 Acyclic sugar-derived dienophiles can undergo highly stereoselective cycloadditions with cyclopentadiene. 

Synthesis by carbon-carbon bond formation between an acyclic sugar derivative and the benzothiazole ring system has also been utilized for the synthesis of these C-nucleosides. In one report, 2,3-O-isopropylidene-D-glyceraldehyde (61) was coupled with 2-trimethylsilylbenzothiazole to afford the A-nucleoside 185 as an intermediate, which underwent a 1,2-shift of the alditolyl chain to produce the C-nucleoside 186 (85TL5477) (Scheme 55). 

The thieno[3,2-d]pyrimidine system of 367 was constructed onto the acyclic sugar derivative 346. This acyclo C-nucleoside (367) did not inhibit a number of DNA and RNA viruses in cell cultures [91JCS(P1)195] (Scheme 105). 

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