Unusual sugar derivative

Aldolases cataly2e the asymmetric condensation of intermediates common in sugar metaboHsm, such as phosphoenolpymvic acid, with suitable aldehyde acceptors. Numerous aldolases derived from plants or animals (Class I aldolases) or from bacteria (Class II) have been examined for appHcations (81). Efforts to extend the appHcations of these en2ymes to the synthesis of unusual sugars have been described (2,81). 

In tandem with his studies of polysaccharides, Stacey had a research group investigating the chemistry of the unusual sugars found as components of carbohydrate macromolecules. In this context, derivatives of simple sugars, di- and trisaccharides, uronic acids, deoxy sugars, amino sugars, sugar sulfates, and phosphates were studied. 

In 1913, Emil Fischer and K. Zach1 discovered a new class of sugar derivatives, the glycals, which have become very important in carbohydrate chemistry because of their unusual reactivity and their ease of transformation and isomerization. After the death of Fischer, the subsequent developments in this field were primarily due to M. Bergmann and his associates, particularly H. Schotte. 

The chemistry of tuberculinic acid (the nucleic acid of the tubercle bacillus) was investigated by Brown and Johnson. The acid was purified by conversion to the copper salt. Distillation with hydrochloric acid yielded small amounts of furfural, indicating the presence of only a trace of pentose in the residue. Levulinic acid was identified, and it was thought on this evidence that the sugar associated with the acid was a hexose. Tuberculinic acid is unique in that it does not contain uracil, has a low pentose content and contains an unusual pyrimidine derivative. The tuberculinic acid was considered to be more nearly related to deoxyribonucleic acid than to ribonucleic acid. ... 

The antibiotic thiolactomycin (43), a fermentation product from a Nocardia species containing an unusual thiolactone moiety was patented as antibiotic no. 2-200 and subsequently reported in the literature in 1982 [73,74]. It resembles a sugar-derived a,/3-unsaturated 4-thioglycono-1,4-lactone and was found to be a broad-spectmm antibiotic [75] by interference with the fatty acid metabolism of bacteria and also inhibited inducible /3-lactamases [76]. A de novo synthesis of the racemate was reported by a Du Pont group in 1984 [77]. Chambers and Thomas [78] reported the synthesis of the (55j-enantiomer in 1989 and concluded from its optical rotation that the natural product is the (5i )-enantiomer. 

The majority of these substances may be considered unique polypeptides which contain unusual amino acids or amino acids joined in some unusual manner. Antibiotics now definitely known to be in this class are the penicillins (2), gramicidin (2), tyrocidine (1), gramicidin-S 3), bacitracin (4), subtilin (-5), polymyxin (6), aerosporin (7) and others. The penicillins are produced by a mold. The others listed here are produced by related bacteria. Streptomycin is a very important antibiotic therapeutically but it does not belong to the polypeptide class, being a complex amino-sugar derivative. 

In a much more complicated piece of work recently disclosed, two stereospecific aldehyde Diels-Alder reactions have been used in preparation of hikosamine derivative 29, a component of the antibacterial compound hizikimycin (Scheme 4-XIII).45k Diene 25 reacted with furfural to give cw-y-pyrone 26, which was transformed in several steps to aldehyde 27. Condensation of 27 with 25 using magnesium bromide as catalyst afforded only adduct 28, presumably via chelated intermediate 27A. Compound 28 was converted in a series of steps to acetylhikosamine 29. The methodlogy described here allowed total synthesis of this unusual sugar having 10 contiguous chiral centers with complete stereocontrol. 

The unusual sugars such as apiose, aceric acid, or KDO require special techniques for their detection and characterization. However, 0-methylated sugars can be characterized by GLC-MS of their alditol acetates (Darvill et al., 1978). Mono-O-methylated derivatives elute faster than their completely acetylated homologues. This can be illustrated by comparison of the retention times (on a SP-1000 glass capillary column) of the acetylated derivatives of xylitol (R-0.71) and 4-0-methylxylitol (R-... 

The crystalline product (45b) is stable for several days at room temperature. It is unusual in being a thio sugar derivative in which the sulfur atom is electrophilic in character, and it offers possibilities for novel synthetic applications. ... 

The sugars from the nucleoside-like antibiotics have been discussed in Section III,5. These are cordycepose (29), D-psicose (30), angustose (33), and amicetose (39). From actinospectacin, the unusual actinospectose (46) was obtained. Hygromycin and hygromycin B have yielded two novel products, 6-deoxy-D-om6mo-hexos-5-ulose (49) and D-talose (51). Novobiocin contains the sugar derivative called noviose (54). 

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