Ribose synthetic route

A ray of hope appeared when a synthetic route was developed in the laboratory of Albert Eschenmoser in Zurich, leading in good yields to ribose-2,4-diphosphate (in racemic form). The starting material was glycol aldehyde, which was phospho-rylated in the 2-position and then incubated with formaldehyde. Unfortunately the synthetic conditions are only those of a modern laboratory, but could the reaction have taken place on the primeval Earth (Muller et al., 1990). 

The synthesis of pentose-2,4-diphosphate referred to above gave the best yields of a ribose derivative. Thus, the search for an effective synthesis leading to necessary starting materials such as glycol aldehyde phosphate (GAP) was important Krishnamurthy et al. (1999, 2000) reported new synthetic routes to GAP glycol aldehyde is allowed to react with amidotriphosphate (AmTP) in dilute aqueous solution. The triphosphate derivative is formed from trimetaphosphate and NH4OH. 

A convenient synthetic route to enantiomerically pure hydroxylated pyrroline-7V-oxides (108) has been reported (292). A key step is the formation of oo-oxo-enoates from D-ribose (107) and the subsequent 1,3-azaprotio cyclo-transfer reaction of the resulting oximino alkenoate derivatives (Scheme 2.43). 

Fig. 32 Synthetic route from D-ribose towards cyclooctane derivative.

More recently, a simple synthetic route for a large scale production of 12 (2,3-0-isopropylidene-L-lyxonolactone) was described [27]. The chosen starting material was D-ribose (13), which was oxidized to the corresponding lactone 14 (Scheme 5). The latter was submitted in situ to acetonation to provide the 2,3-0-isopropylidene derivative 9, which was then mesylated at OH-5. Treatment of the crude 5-0-mesylate 15 with potassium hydroxide led to 12 according to the mechanism proposed in Scheme 5. 

Biosynthetic processes Elongation of RNA or DNA chains Other synthetic routes RNA polymerase I DNA polymerase Poly(ADP-ribose)polymerase Carbamoyl phosphate synthetase Anthranilate synthase-phosphoribosyl transferase Glycogen synthetase Methionyl-tRNA synthetase ATP phosphoribosyl transferase Zn2+... 

Several general synthetic routes for the preparation of 2-desoxy-D-ribose have been described. 

The quest for synthetic routes to ribose continued. The reduction of the high pH in the formose reaction was made possible by adding Mg(OH)2 the aldopentoses obtained were more stable, but the reaction was slower. The search for more effective catalysts led to Pb2+ ions. The first mention of this possibility was made by Wolfgang Langenbeck (University of Halle) as early as 1954 (Langenbeck, 1954). 

The synthesis of 3,4-di-0-acetyl-2,6-dideoxy-6,6,6-trifluoro-a-L-/yxo-hexopyra-nosyl bromide from D-lyxose features the use of timethylsilyltrifluoromethane in the presence of fluoride ion to effect the addition of the trifluoromethyl group to an aldehyde. Similar methodology has been utilized in the synthesis of 5-deoxy-5,5,5-trifluoro-D-lyxose, -L-ribose, -L-arabinose and -D-xylose. A symposium report has looked at synthetic routes to 6-deoxy-6,6,6-trifluorosugars and the synthesis of racemic 3-deoxy-2-C-trifluoromethyI-er> //tro and -threo -pentofura-noses is covered in Chapter 14. 

Ribonucleic Acid. A major contribution to the formulation of RNA structure was the demonstration that alkaline hydrolysis of RNA quantitatively liberates about equal amounts of mononucleotide isomers of all four bases 103). Although it was readily established that none of these mononucleotides is the 5 -phosphate isomer, it was not until some years later that Cohn and associates 103) by controlled degradation experiments, and Brown and associates 121) by the synthetic route, established that the products were isomers involving phosphate attachment at positions 2 and 3 of the ribose. Of equal significance was the discovery 161) that hydrolysis of RNA by the enzyme phosphodiesterase (snake venom or intestinal) liberates mononucleotides exclusively of still another type, the 5 -mono-nucleotides. It was thus necessary to establish the mechanisms which could account for one phosphodiester structure in the RNA chain giving rise to three isomers of each mononucleotide. 

Midtkandal et al reported a facile and new synthetic route to a C-nucleoside, 2-deo>y benzamide riboside (21). The synthesised target was found to be active against a number of cancer cell lines. Similar ribose-based C-nucleosides are known as antiviral and antiproliferative drugs, such as formycin, tiazofurin and benzamide riboside. 

Another promising route was reported in patent and open hterature by both DSM and Diversa [13, 14]. This route employs a 2-deoxy-D-ribose 5-phosphate aldolase (DERA) that catalyzes a tandem aldol addition in which two equivalents of acetaldehyde (AA) are added in sequence to chloroacetaldehyde (CIAA) to produce a lactol derivative that is similar to the 3,5-dihydoxy side chain of synthetic statins (Figure 6.2e). Diversa screened environmental libraries for novel wild-type DERAs and identified an enzyme that was both tolerant to increased substrate concentrations and more active than DERA from E. coli in the target reaction [13]. 

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