Tetroses and Pentoses

1 Tetroses and Pentoses. - A new synthesis of 2-0-benzyl-3,4-0-iso-propylidene-D-erythrose (2) from 2,3-0-isopropylidene-D-glyceraldehyde involved chain-extension by use of methyl tolyl sulfoxide, followed by benzylation of the new hydroxyl group to give 1. Quantitative transformation of the sulfoxide to a formyl group (l- 2) was achieved by exposure to lutidine-trifluoroacetic anhydride, then aq. sodium hydrogen carbonate.  

Compound 3 was prepared from commercially available (/ )-(- -)-5-hy-droxymethyl-5H-furan-2-one by 0-benzylation and subsequent conjugate addition of (PhMe2Si)2 Cu(CN)Li2, and converted to 2-deoxy-L-ribose (5) via the 2-deoxy-L-ribonolactone derivative 4 2 -Deoxy-D-ribose 5-phosphates Relabelled at C-3 and C-4, and/or at C-5, were prepared in a chemoenz3miatic approach by cyclizing appropriately labelled dihydroxyacetone monophosphates with unlabelled acetaldehyde. By use of [ 2]-, or [2- RC]- 

1 Tetroses and Pentoses. - The application of the Strecker synthesis to the preparation of 2-amino-2-deoxytetrose derivatives is covered in Chapter 9 and a lipase-mediated route to 4-carbon diols and triols is referred to in Chapter 18. 

The CaQa/KOH-promoted aldol condensation of dihydroxyacetone with 

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Derivatives of trioses, tetroses, and pentoses and of a seven-carbon sugar (sedohepmlose) are formed as meta-bohc intermediates in glycolysis and the pentose phosphate pathway. Pentoses are important in nucleotides. 

The reaction is autocatalytic and proceeds in stages through glycolal-dehyde, glyceraldehyde, and dihydroxyacetone, tetroses, and pentoses to give finally hexoses including glucose and fructose. One proposed re-... 

Triose, tetrose, and pentose phosphates enriched with C have been prepared by the Kiliani-Fischer reaction on the terminal phosphates of the next lower aldose. The mixed nitriles were separated on Dowex 1-X8 resin and reduced with hydrogen over Pd-BaS04. The synthesis of D-glucose 2-phosphate by phosphorylation of l,3,4,6-tetra-0-acetyl-j3-D-glucopyranosyl chloride, itself prepared by 2 1 acetyl migration, has been reported. Rates of phosphate hydrolysis in 0.25 M sulphuric acid and in 0.25 M sodium hydroxide were measured for D-glucose monophosphates in the former the order was 1-phosphate > 2-phosphate > 3-phosphate > 6-phosphate while in the latter it was 3-phosphate > 6-phosphate > 2-phosphate > 1-phosphate. ... 

Tetroses and Pentoses - 4-0- -Butyldimethylsilyl-2,3-0-isopropylidene-L-threose (1) has been prepared in seven efficient steps from o-xylose. 3,4-0-Isopropylidene-D-eythrulose (4) has been synthesized from the known tetritol derivative 2 by primary protection as the silyl ether 3, followed by Dess-Martin oxidation and desilylation. Compound 2 was derived from D-isoascorbic acid (see Vol. 22, p. 178, refs. 9,10). In a similar reaction sequence, the enantiomer 5 has been obtained from L-ascorbic acid. The dehomologation of several di-0-isopropylidenehexofuranoses e.g., 6- 7) has been carried out in two steps without intermediate purification, by successive treatment with periodic acid in ethyl acetate, followed by sodium borohydride in ethanol. Selective reduction of 3-deoxy-D-g/jcero-pentos-2-ulose (8) to 3-deoxy-D-g/> cero-pent-2-ose (9) has been achieved enzymically with aldose reductase and NADPH." 4-Isopropyl-2-oxazolin-5-one (10) is a masked formaldehyde equivalent that is easily converted to an anion and demasked by mild acid hydrolysis. One of the three examples of its use in the synthesis of monosaccharides is shown in Scheme 1. ... 

Further studies of the formose reaction have been reported. Alkaline-earth metal hydroxides initiated zero-order reactions at intermediate conversions of formaldehyde, and the formation of glyceraldehyde or tetroses and pentoses, etc., from formaldehyde in the presence of calcium hydroxide depended on whether or not glycolaldehyde was present. Self-condensation of formaldehyde in the presence of alkaline-earth metal hydroxides has also been studied in the absence and in the presence of a co-catalyst such as D-glucose and in the presence of glycolaldehyde. Self-condensation of formaldehyde in the presence of lead(ii) oxide appears to involve a soluble complex in which the lead atom co-ordinates with the carbonyl oxygen atom of formaldehyde. " The catalytic functions of calcium ion species in a homogeneous formose reaction and the distribution of products in a photochemical formose reaction have been investigated. 

This technique, in combination with an inversion of configuration of the carbon adjacent to the thiazole ring, has been eir rloyed for the chain extension of o-glyceraldehyde acetonide (2) into all possible tetrose and pentose homologs (eq 11). 

Many of the simple trioses, tetroses, and pentoses do not occur naturally in the free state but are commonly found as phosphate-ester derivatives. The phospho-esters are important intermediates in the breakdown and synthesis of carbohydrates by living organisms. D-Glucose is converted into D-fructose-l,6-bisphos-phate that is then cleaved in half to give D-glyceraldehyde-3-phosphate and dihydroxy acetone phosphate (see Chapter 11). D-Erythrose is found as the 4-phosphate in the pentose-phosphate pathway of carbohydrate degradation and in the photosynthetic process. D-Ribose-5-phosphate, D-ribulose-5-phosphate, D-xy-lose-5-phosphate, and D-xylulose-5-phosphate are found in the pentose phosphate pathway as well as in the photosynthetic pathway (see Chapter 10). D-Ribulose-1,5-bisphosphate is the direct intermediate to which CO2 is added in the photosynthetic pathway. D-Ribose-5-phosphate also is the precursor of RNA (ribonucleic acid) and DNA (deoxyribonucleic acid). See Fig. 1.7 for the structures of these common sugar phosphates. 

Aldose sugars make up a large part of the carbohydrate family, but the ones that are really worth knowing are part of the D-family. The simplest of these D-sugars is the triose glyceraldehyde. From there you have 2 tetroses, 4 pentoses, and 8 hexoses. Each of these aldose sugars has an enantiomer. 

The direct homologation technique was then extended to the synthesis of various uncommon carbohydrate structures. Thus, higher sugars of the L-series were obtained Starting from 2,3-0-isopropylidene-4-O-benzyl-L-threose (43) [39c] (Scheme 13), and the amino tetrose 47 and pentose 48 were prepared from the a-amino aldehyde 46 derived from L-serine [46a] (Scheme 14). These amino sugars were used as chiral building blocks for the... 

A. Dondoni, J. Orduna, and P. Merino, Construction of all 0-alkoxy D-tetrose and D-pentose stereoisomers from 2,3-0-isopropylidene-D-glyceraldehyde using 2-(trimethylsilyl)thiazole as a formyl anion equivalent. Synthesis p. 201 (1992). 

TPP is also the coenzyme in the transketo-lase reaction (Fig. 8.27) found in the pentose phosphate pathway that interconverts hex-oses, pentoses, tetroses, and trioses. This reaction removes carbons 1 and 2 of a ketose and transfers them to an acceptor aldose. Examples include TPP transferring carbons 1 and 2 of xylulose-5-P to ribose-5-P, producing glyc-eraldehyde-3-P (5 carbons minus 2 carbons) and sedoheptulose-7-P (5 carbons plus 2 carbons). This reaction is reversible. A second reversible reaction has TPP transferring carbons 1 and 2 of xylulose-5-P to erythrose-4-P, producing fructose-6-P (4 carbons plus 2 carbons) and glyceraldehyde-3-P (5 carbons minus 2 carbons). 

More recently Wong reported the study on a KDO aldolase isolated from Auereobacterium barkerei. The enzyme has been proved as a versatile catalyst in the synthesis of KDO and its analogues [65] (Scheme 8). This enzyme accepts hexoses, pentoses, tetroses and even trioses as substrates. Various aldol reactions were conducted on a preparative scale with significant success. KDO (7) was obtained from D-arabinose in 67% yield [65], The enzyme was found to be specific for substrates having -configuration at C-3, whereas the stereochemical requirements at C-2 were less important. In all cases observed so far,... 

The carbon chain of an aldose can be increased by one carbon in a Kiliani-Fischer synthesis. In other words, tetroses can be converted into pentoses, and pentoses can be converted into hexoses. 

The Ruff degradation is the opposite of the Kiliani-Fischer synthesis. Thus, the Ruff degradation shortens an aldose chain by one carbon Hexoses are converted into pentoses, and pentoses are converted into tetroses. In the Ruff degradation, the calcium salt of an aldonic acid is oxidized with hydrogen peroxide. Ferric ion catalyzes the oxidation reaction, which cleaves the bond between C-1 and C-2, forming CO2 and an aldehyde. It is known that the reaction involves the formation of radicals, but the precise mechanism is not well understood. 

The polarographic behavior of the trioses and tetroses differs from that of pentoses and hexoses because of their structural differences in solution. Whereas pentoses and hexoses exist in solution almost exclusively in their cyclic, hemiacetal forms, trioses afford only the hydrated, acyclic forms. Trioses form dimers in the crystalline form, but these quickly revert to the monomers in aqueous (especially alkaline) solutions, where they are polarographically active, " so that the dimeric forms need not be considered in polarographic studies. Aldotetroses, as types intermediate between trioses and pentoses, exist both as their furanoid forms and as the hydrated, acyclic forms. It is evident that the ketotetroses (n- and L-gZycero-tetrulose) do not afford cyclic forms in solution, and exist only in the acyclic, possibly hydrated, form. 

Nagakawa and co-workers investigated the use of simple acetylenic alcohols for the synthesis of trioses, tetroses, and l-deoxy-eo f/t/ o-pentose. 

Most monosaccharides are aldoses, and almost all natural monosaccharides belong to the D series. The family of d aldoses is shown in I Figure 7.8. D-glyceraldehyde, the smallest monosaccharide with a chiral carbon, is the standard on which the whole series is based. Notice that the bottom chiral carbon in each compound is directed to the right. The 2" formula tells us there must be 2 trioses, 4 tetroses, 8 pentoses, and 16 hexoses. Half of those are the d compounds shown in Figure 7.8. The other half (not shown) are the enantiomers or l compounds. 

Glycoses are classified by the total number of carbon atoms. The glycose with three carbon atoms (2, n = 1) is called a triose, and when there are four carbon atoms (2, n = 2), it is a tetrose. A pentose has five carbon atoms (2, n = 3) and a hexose has six carbon atoms (2, n = 4). If the carbonyl unit in 2 is an aldehyde, it is an aldose (see preceding discussion) thus, a three-carbon aldose is an aldotriose and a six-carbon aldose is an aldohexose. If the carbonyl unit in 2 is a ketone unit, the molecule is a ketotetrose, a ketohexose, etc. 

Figure III-A. The relationship of d-(-f) glyceraldehyde to D-tetroses, D-pentoses, and d-hexoses. The projections shown here are in linear (Fischer type), flat-cyclic (Haworth type), and three-dimensional type representations. All are used interchangeably as needed.

If glyceraldehyde is a triose,. ... ..then this compound s a tetrose.... ..and this one is a pentose... 

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