Pentoses 2-deoxy, syntheses

Ness, R. K., and H. G. Fletcher, Jr. 2-Deoxy-D-er> f/iro-pentose. X. Synthesis of l,4-Anhydro-3,5-di-0-benzoyl-2-deoxy-D-er> //iro-pentose-l-enol. Derivatives of a Furanose-related Glycal. J. Organ. Chem. (U.S.A.) 28, 435 (1963) Haga, M., and R. K. Ness Preparation and Properties of 3,5-Di-0-p-anisoyl-l,2-dideoxy-D-er> t/iro-pentofuranose-l-ene. Various p-Anisoylated Derivatives of D-Ribofuranose. J. Organ. Chem. (U. S. A.) 30, 158 (1965). 

A more complicated reaction sequence has been used by Ukita and Nagasawa (59) in their synthesis of 2-deoxy D-ribose 5-phosphate (2-deoxy D-erythro-pentose 5-(dihydrogen phosphate)), (29). They phosphorylated a mixture of the anomeric methyl deoxyribofuranosides (24)... 

On their side, Yin and Linker [216] made use of a 2-C-branched hexopyranoside, the synthesis of which was achieved by addition of dimethyl malonate to tri-O-benzyl-D-glucal (TUPAC name 3,4,6-tri-0-benzyl-l,5-anhydro-2-deoxy-D-araZtino-hex-l-enitol, Scheme 45) [217], Thus, saponification of the 2-C-[bis(meth-oxycarbonyl)]methyl derivative 184 to the corresponding malonic acid 185 was followed by heating in refluxing toluene. This led to decarboxylation and lactoniza-tion giving 186. The method was optimized and applied to the synthesis of pentoses and disaccharides. 

Deoxy-D-arabino-hexose 3% HiEff8-BP 200 synthesis of 2-deoxy-L-erythro-and -D-fhreo-pentose 390... 

An elegant, stereospecific synthesis of two 2-chloro-2-deoxy-pentoses was achieved during the course of a study of the anomerization of chlorosulfated glycosyl chlorides.40 It had been found37 that attempts to anomerize /3-D-xylopyranosyl chloride 2,3,4-tri(chloro-sulfate) (14) with 0.25 mol-equivalent of aluminum chloride afforded the crystalline a-D anomer only in low yield formed also was another compound whose structure has been established40 to be that of 2-chloro-2-deoxy-a-D-lyxopyranosyl chloride 3,4-di(chlorosulfate) (16). The dichloro derivative 16 became the exclusive product when 1.5 mol-equivalents of aluminum chloride were used treatment of 16 with sodium iodide yielded crystalline 2-chloro-2-deoxy-D-lyxose. Similarly, a-D-lyxopyranosyl chloride 2,3,4-tri(chlorosulfate) (15) afforded 2-chloro-2-deoxy-a-D-xylopyranosyl chloride 3,4-di(chlorosuI-fate) (17). 

Pentenal was employed30 for an effective synthesis of the 2,3-di-deoxy-DL-pentose (50a). The aldehyde was converted into the dimethyl acetal 48 this was ci.s-hydroxylated with potassium permanganate to give diol 49. Mild, acid hydrolysis of 49 afforded the methyl... 

Another stereospecific synthesis of2-deoxy-DL-en/tfiro-pentose was based10 on cis-l-(tetrahydropyran-2-yloxy)-2-penten-5-ol (156) as the substrate. cts-Hydroxylation of 156, followed by oxidation of the unprotected, primary hydroxyl group to an aldehyde group according to Barton s procedure, yielded the desired sugar 2 in low yield. 

Hough343 described a synthesis of 2-deoxy-D-en/f/oopentose that was based on the reaction of 638 with allylmagnesium bromide, cis-hydroxylation of the product, and cleavage of the 1,2-diol system in 639 with sodium metaperiodate. Although a mixture of two dia-stereomers should have been formed, 2-deoxy-D-< n/f/iro-pentose was the main product of the reactions, a result consistent with expectations based on Cram s rule of 1,2-induction. 

PRPP is an "activated pentose" that participates in the synthesis of purines and pyrimidines, and in the salvage of purine bases (see p. 294). Synthesis of PRPP from ATP and ribose 5-phosphate is catalyzed by PRPP synthetase (ribose phosphate pyrophosphokinase, Figure 22.6). This enzyme is activated by inorganic phosphate (Pi) and inhibited by purine nucleotides (end-product inhibition). [Note The sugar moiety of PRPP is ribose, and therefore ribonucleotides are the end products of de novo purine synthesis. When deoxy-ribonucleotides are required for DNA synthesis, the ribose sugar moiety is reduced (see p. 295).]... 

The six-carbon chain of ManNAc 6-P can be extended by three carbon atoms using an aldol-type condensation with a three-carbon fragment from PEP (Eq. 20-7, step c) to give N-acetylneuraminic acid (sialic acid).48 Tire nine-carbon chain of this molecule can cyclize to form a pair of anomers with 6-membered rings as shown in Eq. 20-7. In a similar manner, arabi-nose 5-P is converted to the 8-carbon 3-deoxy-D-manno-octulosonic acid (KDO) (Fig. 4-15), a component of the lipopolysaccharide of gram-negative bacteria (Fig. 8-30), and D-Erythrose 4-P is converted to 3-deoxy-D-arafrmo-heptulosonate 7-P, the first metabolite in the shikimate pathway of aromatic synthesis (Fig. 25-1).48a The arabinose-P used for KDO synthesis is formed by isomerization of D-ribulose 5-P from the pentose phosphate pathway, and erythrose 4-P arises from the same pathway. 

On applying the Kiliani cyanohydrin synthesis to 2 deoxy-i>-erythro-pentose, Wood and Fletcher127 obtained crystalline 3-deoxy-D-ribo-hexose and 3-deoxy-D-arabino-hexose (as the dithioacetal). Interesting comments concerning the course of the Kiliani synthesis were made by these authors. Condensation127 of 2-deoxy-D-erj/(Aro-pentose with nitromethane gave epimeric 1,3-didcoxy-l-nitrohexitols which, after hydrolysis under Nef... 

In vivo, pyruvate lyases perform a catabolic function. The synthetically most interesting types are those involved in the degradation of sialic acids or the structurally related octulosonic acid KDO, which are higher sugars typically found in mammalian or bacterial glycoconjugates [62-64], respectively. Also, hexose or pentose catabolism may proceed via pyruvate cleavage from intermediate 2-keto-3-deoxy derivatives which result from dehydration of the corresponding aldonic acids. Since these aldol additions are freely reversible, the often unfavourable equilibrium constants require that reactions in the direction of synthesis have to be driven by an excess of one of the components, preferably pyruvate for economic reasons, in order to achieve a satisfactory conversion. 

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. 

This reagent remains very useful, and it was recently used for an efficient synthesis of 2-deoxy-L-eryt/ ro-pentose (9), starting from L-arabinose (Scheme 2).16... 

A general method for the synthesis of 2-deoxyaldoses utilizes a reaction sequence involving the formation and subsequent reduction of ketene dithioacetal intermediates (Scheme 10). Reduction of ketene diethyl dithioacetal 12 with lithium aluminum hydride proceeds via the alkoxyaluminum hydride salt involving the 3-hydroxyl group. Several deoxy hexoses and pentoses were prepared by this method, and also their 2-deuterio analogues.45... 

Dideoxy-D-eryt/zro-hexopyranose (172) has been obtained from 3-deoxy-D-eryt/zro-pentose (171, Scheme 51)248 as an intermediate for the synthesis of the lactone moiety of inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase, that lowers cholesterol levels. 

Y. Chong and C. K. Chu, Efficient synthesis of 2-deoxy-L-eryt/fro-pentose (2-deoxy-L-ribose) from L-arabinose, Carbohydr. Res., 337 (2002) 397 102. 

Z. Witczak and R. L. Whistler, A convenient synthesis of 3-deoxy-D-eryt/)ro-pentose, Carbo-hydr. Res., 110 (1982) 326-329. 

M. Helliwell, I. Phillips, R. G. Pritchard, and R. J. Stoodley, Asymmetric synthesis of (5S)-4-deoxy-5-C-(4-nitrophenyl)-L-threo-pentose and (5R)-5-C-(4-nitrophenyl)-L-arabinose, Tetrahedron Lett., 40 (1999) 8651-8655. 

Mode of synthesis A. cyanohydrin, by way of 2-nmino-2-deoxy-aldonic acid B. scission of sugar derivative epoxide with ammonia C. interconversion of hexosamine series D. hemihydrogenation of a-amino nitrile466 E. rearrangement of ketosyl-amine F. Removal of last carbon atom of hexosamine G. Hydrazinolysis (with inversion) of 2-0-tosyl-pentose. 6 Physical constants taken from this reference. c Derivatives (only) isolated. 

---