Octulosonic acid preparation

These results have been used to prepare key starting compounds 11 and 12 for the enantioselective synthesis of 3-deoxy-D-manno-2-octulosonic acid... 

Carbohydrate lactones have been used as the carbonyl reagent in the Reformatsky reaction. Thus, 2,3 5,6-di-O-cyclohexylidene-D-mannono-1,4-lactone [44, obtained by oxidation of the mannofuranose derivative (49)] reacted with ethyl bromoacetate and zinc to give the protected 2-deoxy-3-octulosonic acid ethyl ester (45a) in 69% yield (50). Ketonic hydrolysis with potassium hydroxide in aqueous methanol, followed by acidification and heating, afforded the 1-deoxyheptulose derivative 45b. Similarly, starting from compound 44, the 1-C-substituted allyl and propar-gyl lactols were prepared on reaction with allyl or propaigyl bromides in the presence of zinc (51). 

A similar ester was prepared from cytidine 5 -triphosphate and 3-deoxy-D-manno-octulosonic acid by use of an enzyme188 from Escherichia coli, but its purification failed because of the extreme lability of this derivative. 

Ethoxycarbonyl-l,3-dithiane (183), easily accessible from ethyl glyoxylate diethyl acetal, can be lithiated-alkylated to afford, after deprotection, a-ketoesters as exemplifies the product 184 (Scheme 53)237. This methodology has been used in the preparation of 3-deoxy-D-manno-2-octulosonic acid (KDO) derivatives238 and of the ABC ring system of manzamine A239. 

The research team of J. Tadanier prepared a series of C8-modified 3-deoxy-P-D-manno-2-octulosonic acid analogues as potential inhibitors of CMP-Kdo synthetase. One of the derivatives was prepared from a functionalized olefinic carbohydrate substrate by means of the Wohl-Ziegler bromination. The stereochemistry of the double bond was (Z), however, under the reaction conditions a cis-trans isomerization took place in addition to the bromination at the allylic position (no yield was reported for this step). It is worth noting that the authors did not use a radical initiator for this transformation, the reaction mixture was simply irradiated with a 150W flood lamp. Subsequently the allylic bromide was converted to an allylic azide, which was then subjected to the Staudinger reaction to obtain the corresponding allylic amine. 

Deoxy-6-thio-D-ff7az7Z7o-2-octulosonic acid (6-thio-Kdo) 370 was prepared via... 

By an analogy to the radical syntheses above, the carbon chain elongation reaction was achieved by Barton et al. [109] in the reaction with ethyl a-trifluoroacetoxy acrylate 165. Under radical conditions 165 was coupled with the ester 164 prepared from pentaacetyl gluconic acid and /V-hydroxy-2-thiopiridone (Scheme 35) to afford an unstable intermediate 166, readily convertible to the unsaturated a,p-keto acid 167. The methoxymercuration-demercuration of 167 gave a low selectivity, providing the mixture of 3-deoxy-4-methoxy-D-man/jo and D-g/wco-octulosonic acids (4 3) in a moderate yield [110]. 

Using butyl glyojgrlate as the dienophile a new strategy to prepare 3-deoxy-D-manno-2-octulosonic acid (KDO), 2-deo) -KDO and thioglyco-side of KDO has even been proposed, starting from a diene derived from D-glyceraldehyde. ... 

Deoxv-6-thio-D-manno-2-octulosonic acid (6-thio-KDO), a potential inhibitor of CHP-KDO synthetase, has been prepared. Its ammonium salt failed however to inhibit this enzyme. 3-Deoxy-5-thiopentopyranoses with branch-points at C-3 have been synthesized from non-carbohydrate precursors (3) (see Vol 20, p 148 for their preparation) as shown in Scheme 1. The Pummerer rearrangement of... 

The derivative (18) of 3-deoxv-L-gulo-2-octulosonic acid has been prepared by NBS-catalysed hydrolysis of a dithioacetal, in a similar manner to the method illustrated in Scheme 6,23 and the octulosonic acid itself has been made via oxidative decarboxylation of lactone (19).24... 

D-mannose derivatives, (see Vol. 22, p. 161).29 a new stereoselective total synthesis of (+)-KDO (27) proceeds via the adduct (28) from 2-furyllithium and isopropylidene-D-glyceraldehyde (Scheme 10).3O A full account has been given of a KDO synthesis by free-radical extension of a mannose derivative at C-6 (see Vol. 22, p. 162),31 and there has been a further report on the preparation of 3-deoxy-L-5(ulo-2-octulosonic acid [the C-7 epimer of (27)] by similar methods to those previously used (see Vol. 22, p. 162).32... 

Sequential aldol trimerisation of acetaldehyde catalysed by aldolases followed by enzymic addition of pyruvic acid has afforded the tetradeoxy-nonulopyrano-sonic acid 26, and the preparation of some 3-deoxy-octulosonic acids and 3-deoxy-heptulosonic acids is discussed in Chapter 2. 

The a- and P-glycopyranosyl phosphates of 3-deoxy-D-ma no-2-octulosonic acid have been prepared from Kdo as inhibitors of 3-deoxy-D-/nowio-2-octuloso-nate-8-phosphate synthase, which occurs in Gram-negative bacteria. iV-Acetyl-neuraminic add has been 0-alkylated at C-4 by selective alkylation of an 8,9-0-isopropylidene derivative, and treatment of the a-benzyl glycoside of N-acetylneuraminic acid with iluoroacetyl imidazole has afforded a mixture of 4,5-and 4,9-di-0-(fluoroacetyl) derivatives. A 4-acetamido-4-deoxy-4-epi-derivative of -acetylneuraminic acid has been prepared using standard techniques. ... 

The carbocyclic analogues of iV-acetylneuraminic acid and 3-deoxy-D-7 ianRo-2-octulosonic acid have been prepared from the Diels-Alder endb-adduct formed between furan and acrylic acid, and the guanidino neuraminic add analogue 75 has been prepared in which the cyclitiol ring was also formed by use of the Diels-Alder reaction. ... 

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