Glyceraldehyde moiety

E) three glyceraldehyde moieties attached to a fatty acid. 

Transfer of dihydroxyacetone moiety from sedoheptulose 7-phosphate onto glyceraldehyde 3-phosphate. This reaction is reversible and is catalyzed by transaldolase according to the scheme ... 

The reaction protocol was further extended to the concise synthesis of poly-oxamic acid, the unique polyhydroxyamino acid side-chain moiety of the antifungal polyoxin antibiotics (63). Treatment of the template 205 under standard thermal cycloaddition conditions with (5)-glyceraldehyde acetonide led to the formation of a single diastereoisomer 208 in 53% yield. Subsequent template removal released polyoxamic acid 209 in essentially quantitative yield. This represents a matched system, with the mismatched system leading to more complex reaction mixtures (Scheme 3.70). 

Terpenes, biogenetically, arise from two simple five-carbon moieties. Isoprenyl-diphosphate (IPP) and dimethylallyldiphosphate (DMAPP) serve as universal precursors for the biosynthesis of terpenes. They are biosynthesised from three acetylcoenzyme A moieties through mevalonic acid (MVA) via the so-called mevalonate pathway. About 10 years ago, the existence of a second pathway leading to IPP and DMAPP was discovered involving l-deoxy-D-xylulose-5-phos-phate (DXP) and 2C-methyl-D-erythritol-4-phosphate (MEP). This so-called non-mevalonate or deoxyxylulose phosphate pathway starts off with the condensation of glyceraldehyde phosphate and pyruvate affording DXP. Through a series of reactions as shown in Fig. 4.1, IPP and DMAPP are formed, respectively [3,7, 42, 43]. 

The formation of deoxyribose, die pentose moiety of deoxyribonucleic acid, can occur directly from ribose while the latter is in the form of a nucleotide diphosphate. Deoxyribose-5-phosphate can also be formed by condensation of acetaldehyde and glyceraldehyde-3-phosphate. 

The isomeric triose phosphates, glyceraldehyde-3-phos-phate and dihydroxyacetone phosphate, bear the same relationship to each other as do glucose-6-phosphate and fruc-tose-6-phosphate. Their interconversion, catalyzed by triose phosphate isomerase, is equally facile (see fig. 12.13). Dihydroxyacetone phosphate is a starting material for the synthesis of the glycerol moiety of fats (chapter 19), but only glyceraldehyde-3-phosphate is used in glycolysis. Thus, under ordinary circumstances nearly all of the dihydroxyacetone phosphate that is formed in the cleavage of... 

Functionally and mechanistically reminiscent of the pyruvate lyases, the 2-deoxy-D-ribose 5-phosphate (121) aldolase (RibA EC 4.1.2.4) [363] is involved in the deoxynucleotide metabolism where it catalyzes the addition of acetaldehyde (122) to D-glyceraldehyde 3-phosphate (12) via the transient formation of a lysine Schiff base intermediate (class I). Hence, it is a unique aldolase in that it uses two aldehydic substrates both as the aldol donor and acceptor components. RibA enzymes from several microbial and animal sources have been purified [363-365], and those from Lactobacillus plantarum and E. coli could be induced to crystallization [365-367]. In addition, the E. coli RibA has been cloned [368] and overexpressed. It has a usefully high specific activity [369] of 58 Umg-1 and high affinity for acetaldehyde as the natural aldol donor component (Km = 1.7 mM) [370]. The equilibrium constant for the formation of 121 of 2 x 10M does not strongly favor synthesis. Interestingly, the enzyme s relaxed acceptor specificity allows for substitution of both cosubstrates propional-dehyde 111, acetone 123, or fluoroacetone 124 can replace 122 as the donor [370,371], and a number of aldehydes up to a chain length of 4 non-hydrogen atoms are tolerated as the acceptor moiety (Table 6). 

Although TA from yeast is commercially available, it has rarely been used in organic synthesis applications, and no detailed study of substrate specificity has yet been performed. This is presumably due to high enzyme cost and also since the reaction equilibrium is near unity, resulting in the formation of a 50 50 mixture of products. In addition the stereochemistry accessible by TA catalysis matches that of FruA DHAP-dependent aldolase and the latter is a more convenient system to work with. In one application, TA was used in the synthesis D-fructose from starch.113 The aldol moiety was transferred from Fru 6-P to D-glyceraldehyde in the final step of this multi-enzyme synthesis of D-fructose (Scheme 5.60). This process was developed because the authors could not identify a phosphatase that was specific for fructose 6-phosphate and TA offered an elegant method to bypass the need for phosphatase treatment. 

Figure 5.4 Outline of the newly discovered glyceraldehyde phosphate/pyruvate pathway for the formation of C5 isoprenoid units. None of the intermediates after 2-C-methyl-D-erythritol 4-phosphate is known. P indicates a phosphate moiety. TPP, thiamine pyrophosphate NADP, nicotinamide adenine dinucleotide phosphate.

Dondoni and coworkers [63] have shown that homologation of a-hydroxycarbaldehydes can be achieved with high antiselectivity by addition of 2-(trimethylsilyl)thiazole (42) (Scheme 13.25). For instance, D-glyceraldehyde acetonide (R)-24 reacts with 42 giving 43 in 96% yields with the anti vs. syn diastereoselectivity better than 95 5. Release of the aldehyde requires protection of the alcohol as a benzyl ether, methylation of the thiazole generates intermediate 43 Me that is not isolated but reduced in situ with NaBH4 to give thiazoline 43 H. Mercury(II)-catalyzed hydrolysis liberate the semiprotected D-erythrose derivative d-45 in 62% overall yield [64]. Methylation of the thiazole moiety can also be achieved with methyl triflate instead of Mel, and copper(II)chloride can be used instead of mercury(II)chloride [65]. 

L-Arcanose and L-olimycose have been prepared in enantiomerically pure forms and with high stereoselectivity by Lewis-acid promoted addition of (5)-2-benzyloxypropanal to 1-tri-methylsilyl-2,3-butadiene. Depending on the nature of the Lewis acid either the syn (with TiCl4) or the anti adduct (with BF3 Et20) can be obtained. Epoxidation with lateral control by the allylic alcohol moieties and standard reactions lead to the unprotected monosaccharides [334]. Total syntheses of 2,3-dideoxy-3-C-methyl-D-maw o-heptose and of 2,3-dideoxy-2,3-di-C-methyl-D-gfycero-D-ga(acto-heptose have been realized by addition of 2-(trimethylsiloxy)furan to 2,3-0-isopropylidene-D-glyceraldehyde ((R)-37) [335]. 

Cytoxazone is a novel cytokine modulator. The total synthesis of this natural product and its enantiomer was accomplished by S. Sugiyama. The 3-amino-1,2-propanediol moiety was synthesized by a Petasis boronic acid-Mannich reaction between DL-glyceraldehyde, (R)-1-(1-naphthyl)ethylamine and 4-methoxyphenylboronic acid to provide a 1 1 mixture of the diastereomeric products. The diastereomers could be separated at a later stage in the synthesis and transformed into (-)- and (+)-cytoxazone. 

To verify the level of stereocontrol that could be potentially achieved by this process, the same authors exploited the presence of a stereocenter a- to the aldox-ime ether moiety derived from 2,3-isopropyhdene-D-glyceraldehyde (665). The expected products were, in this case, 3,4,5-trisubstituted y-lactones (666). The trans-trans products were obtained in all three of the reported examples, in good to excellent yields and with good stereoselectivity (8 1 ds) (Scheme 138). 

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