Synthesis from erythrose

4 Synthesis from erythrose a-Homonojirimycin (1) has been synthesized from the erythrose derivative by Sharpless asymmetric epoxidation to the 5y -epoxide 48 

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Synthesis from erythrose An efficient approach for the synthesis of (-l-)-trihy-droxyheliotridane (180) via a chiral erythrose derivative has been reported (Scheme 16). Wittig reaction of 2,3-(9-isopropylidene-L-erythrose (172) with Ph3P=CHCH=CHC02Et produced a 1 5 mixture of the ( , )-173 and (Z,A)-174 isomeric dienes, respectively. The diene 173 could be quantitatively obtained by isomerization of 174 with E. The diene 174 was converted to the azide 177, which upon boiling in benzene gave the vinyl aziridine 176. Pyrolysis of 176 furnished the pyrrolizidine 178. On the other hand, the diene 173 was... 

Deoxy-araWno-heptulosonic acid 7-phosphate (10) is a metabolic intermediate before shikimic acid in the biosynthetic pathway to aromatic amino-acids in bacteria and plants. While (10) is formed enzymically from erythrose 4-phosphate (11) and phosphoenol pyruvate, a one-step chemical synthesis from (11) and oxalacetate has now been published.36 The synthesis takes place at room temperature and neutral pH... 

In the third reaction, transketolase catalyzes the synthesis offructose 6-phosphate and glyceraldehyde 3-phosphate from erythrose 4-phosphate and xylulose 5-phosphate. 

Synthesis from o-erythrose The synthesis of 1 has been achieved from D-erythrose via its 2,3-0-isopropylidene derivative (Scheme 15). Reaction of... 

Synthesis from o-erythrose The D-erythrose derivative 9 has been used for the synthesis of (15, 2i ,8ai )-l,2-dihydroxyindolizidine (13) by transformation into the azide 10 (Scheme 2). Intramolecular cycloaddition of 10 in boiling benzene produced the bi-cyclic iminium ion 11, which underwent sodium borohydride reduction to give 12, followed by acid hydrolysis of the isopropylidene group to provide 13 in 49% overall yield from 10. 

Besides showing the unbranched pathway from erythrose-4-phosphate and phosphoenolpyruvate to shikimic acid. Figure 2L13 also shows the sequence of reactions from shikimic acid to chorismate, the first major branch point in the synthesis of the aromatic amino acids and histidine. The sixth reaction of the shikimic acid pathway is inhibited specifically by glyphosate (see here), which is the active ingredient in the broad spectrum herbicide known as Roundup. 

Figure 21.12 provides an overview of the biosynthesis of aromatic amino acids and histidine. All of the carbons in phenylalanine and tyrosine are derived from erythrose-4-phosphate and phosphoenolpyruvate. A key intermediate in synthesis of virtually all aromatic compounds (including p-aminobenzoic acid) in plant and bacterial cells is shikimic acid. Shikimic acid gives rise to chorismate... 

Preparation (4, 4S). D-Ribose may be synthesized from D-arabinose by alkaline isomerization, by the glycal synthesis, or through the pyridine-catalyzed epimerization of D-arabonic acid followed by reduction. The sugar also has been prepared by the oxidative degradation of calcium D-altronate (44) and by the nitromethane synthesis from D-erythrose (4 ). 

A one pot enzymatic synthesis of (6/ )- and (65 -fluoroshikimic acid from erythrose 4-phosphate and both isomers of 3-fluorophosphoenolpyruvate in the presence of 3-deoxy-D-ara mo-heptulosonic acid 7-phosphate synthase, followed by treatment with 3-dehydroquinate synthase and dehydroquinase simultaneously, then finally shikimate dehydrogenase has been described. ... 

With the same synthetic sequence, labeled ribose molecules produced AIRs labeled on the ribose moiety. From D-erythrose and (l3C)NaCN, the Fischer-Kiliani synthesis, as modernized by Serianni et al.59 produced D-(l-l3C)ribose and D-(l-l3C)arabinose. The labeled arabinose was transformed into D-(2-l3C)ri-bose in the presence of dioxobis(2,4-pentanedionato)-0-0 -molybdenum(VI) in... 

The borohydride reduction-periodate cleavage applied to 2,3-O-isopro-pylidene-D-ribono- 1,4-lactone (16a) led to L-erythrose (30). The method was also employed (31) for the synthesis of D-erythrose, starting from an Obenzylidene-D-ribonolactone. However, in this case, the structural assignments for the intermediate compounds must be revised, as the starting material formulated as 3,5-O-benzylidene-D-ribono-1,4-lactone (2) was, as discussed previously in this section, the 3,4-0-benzylidene-D-ribono-1,5-lactone (3a). Therefore, the correct structure for the product described as 3,5-O-benzylidene-D-ribitol (20, not isolated) would be 3,4-O-benzylidene-... 

We have extended our work on a new synthesis of the antiprotozoal antibiotic anisomycin to the necine bases of the pyrrolizidine alkaloids, in particular retronecine and crotanecine. The key intermediate, (2R,3S,4R)-2-(alkoxy-carbonylmethyl)-3,4—isopropylidenedioxypyrrolidine, has been prepared by three distinct routes from D-ribose and g-erythrose, using reactions of high stereoselectivity. 

Alkaloid biosynthesis needs the substrate. Substrates are derivatives of the secondary metabolism building blocks the acetyl coenzyme A (acetyl-CoA), shikimic acid, mevalonic acid and 1-deoxyxylulose 5-phosphate (Figure 21). The synthesis of alkaloids starts from the acetate, shikimate, mevalonate and deoxyxylulose pathways. The acetyl coenzyme A pathway (acetate pathway) is the source of some alkaloids and their precursors (e.g., piperidine alkaloids or anthraniUc acid as aromatized CoA ester (antraniloyl-CoA)). Shikimic acid is a product of the glycolytic and pentose phosphate pathways, a construction facilitated by parts of phosphoenolpyruvate and erythrose 4-phosphate (Figure 21). The shikimic acid pathway is the source of such alkaloids as quinazoline, quinoline and acridine. 

Buchanan et al. (48) reported a new route to the synthesis of the chiral hydroxy-pyrrolidines 234 and 238 from D-erythrose (230) via an intramolecular cycloaddition of an azide with an alkene (Scheme 9.48). Wittig reaction of the acetonide 230 with (carbethoxyethylene)triphenylphosphorane gave the ( ) and (Z) alkenes 231 and 232. On conversion into the triflate followed by its reaction with KN3, the ( ) isomer 231 allowed the isolation of the triazoline 234 in 68% overall yield, which on treatment with sodium ethoxide afforded the diazo ester 235 in 86% yield. 

Pearson and Lin (52) developed an elegant approach to the synthesis of optically active ( )-swainsonine (247) from isopropylidene-D-erythrose (242) (Scheme 9.52). Wittig reaction of the acetonide 242 led to the (Z) alkene 252 in 86% yield. The chloro alcohol 252 was converted to the azide 253 in 76% yield, which subsequently underwent 1,3-dipolar cycloaddition, isomerization and hydroboration-oxidation to give the indolizidine 255 in 70% overall yield. Cleavage of the acetonide unit in 255 using 6 N HCl gave the target molecule 247 in 85% yield. 

In these tissues the cycle may operate as indicated in Fig. 17-8A with the C3 product also being used in biosynthesis. Furthermore, any of the products from C4 to C7 may be withdrawn in any desired amounts without disrupting the smooth operation of the cycle. For example, the C4 intermediate erythrose 4-P is required in synthesis of aromatic amino acids by bacteria and plants (but not in animals). Ribose 5-P is needed for formation of several amino acids and of nucleic acids by all organisms. In some circumstances the formation of ribose 5-P may be the only essential function for the pentose phosphate pathway.120... 

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. 

Aromatic compounds arise in several ways. The major mute utilized by autotrophic organisms for synthesis of the aromatic amino acids, quinones, and tocopherols is the shikimate pathway. As outlined here, it starts with the glycolysis intermediate phosphoenolpyruvate (PEP) and erythrose 4-phosphate, a metabolite from the pentose phosphate pathway. Phenylalanine, tyrosine, and tryptophan are not only used for protein synthesis but are converted into a broad range of hormones, chromophores, alkaloids, and structural materials. In plants phenylalanine is deaminated to cinnamate which yields hundreds of secondary products. In another pathway ribose 5-phosphate is converted to pyrimidine and purine nucleotides and also to flavins, folates, molybdopterin, and many other pterin derivatives. 

Good yields are obtained at all stages of this synthesis of 2-desoxy-D-ribose, and for preparative purposes Sowden167 claims that the isolation of intermediates is unnecessary. The method would be a valuable one for the preparation of 2-desoxy-D-ribose if D-erythrose were obtainable in a pure state in large quantities. Overend and coworkers1 8 have investigated various methods for the preparation in bulk of this tetrose from easily accessible materials, but a completely satisfactory method is still required. 

The final reaction to be covered in this section is known as the Kiliani-Fischer synthesis. It is a method that converts an aldose to two diastereomeric aldoses that contain one more carbon than the original sugar. The Kiliani-Fischer synthesis is illustrated in the following reaction sequence, which shows the formation of the aldopentoses D-ribose and D-arabinose from the aldotetrose D-erythrose ... 

Isopropylidene-D-erythronolactone and the corresponding lactol, 2,3-0-isopropylidene-D-erythrose are useful chiral synthons in the total synthesis of certain natural products such as the leukotrlenes.4 The lactol is readily available from the lactone, in excellent yield, by reduction with diisobutylalumlnum hydride.4 2,3-0-Isopropylidene-L-erythrose has been employed as the starting material in an enantioselective synthesis of (+)-15S-... 

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