Uridine 5-trityl

These were originally prepared by Khorana as selective protective groups for the 5 -OH of nucleosides and nucleotides. They were designed to be more acid-labile than the trityl group because depurination is often a problem in the acid-catalyzed removal of the trityl group. Introduction of p-methoxy groups increases the rate of hydrolysis by about one order of magnitude for each p-methoxy substituent. For 5 -protected uridine derivatives in 80% AcOH, 20°, the time for hydrolysis was... 

Acetyl-5 -0-trityl-uridin-3 - -dibenzylester XII/2, 197 -acylamid-diamide... 

Direct experimental confirmation of the conclusion that position(l ) is not the point of union was provided in 1934 by Levene and Tipson," who succeeded in methylating the pyrimidine residue without methylating the ribose residue. The methylating agent employed was diazomethane in dry ether and the uridine derivative chosen for methylation was 2,3-diacetyl-5-trityl-uridine (since all its sugar hydroxyls are substituted and it is soluble in dry ether). On hydrolysis of the acetyl and trityl groups from the product a monomethyl-uridine was obtained. This proved to be iV(T)-methyl-uridine since on hydrolysis 1-methyl-uracil, identical with the synthetic product, was isolated. 

This formulation has been confirmed by a study of trityl-uridine, a substance first isolated (in a highly impure state) by Bredereck" in 1932 and assumed by him, without direct experimental evidence, to be 6-trityl-uridine. Levene and Tipson - succeeded in separating the crude material into two crystalline substances, one a monotrityl- and the other a ditrityl-uridine. Furthermore they found that treatment of the monotrityl-uridine with trityl chloride gives the ditrityl derivative. The structure of the monotrityl-uridine was determined as follows. On... 

By analogy with the purine nucleotides of ribosenucleic acid it seems probable that the phosphoryl group is situated at position (3) of the ribose chain, but no direct experimental evidence has yet appeared. Uridylic acid has been synthesized by the action of phosphorus oxychloride on uridine in the presence of barium hydroxide solution and by phosphorylation of 5-trityl-uridine but, unfortunately, these syntheses shed no light on the question. Furthermore, the fact that uridylic acid condenses with trityl chloride to give a trityl-uridylic acid does not prove its structure, though it suggests that position (5) of uridylic acid is free. This tentative conclusion is strengthened by the observation that neither of the pyrimidine nucleotides forms a complex with boric acid. 

To date, the sugar ring structure of only one desoxyribosyl nucleoside (namely, thymidine) is known. In 1935, Levene and Tipson - found that thymidine condenses with trityl chloride in the presence of dry pyridine to give a crystalline monotrityl-thymidine. From their previous proof of the structure of monotrityl-uridine as the 5-trityl ether, it seemed probable that the thymidine ether is 5-trityl-thymidine. This was confirmed by tosylation, to give tosyl-trityl-thymidine, followed by treatment with sodium iodide in acetone under standard conditions. 

In a synthesis of coenzyme uridine-diphosphate-glucose (UDPG), Todd and coworkers protected the primary 5-hydroxyl group of uridine (5) by tritylation, benzylated the 2- and 3-hydroxyl groups (6), and removed the trityl group with 80% acetic acid. 

A 2, 3 -unsaturated derivative of uridine was prepared by base-catalyzed elimination of the methylsulfonyloxy group of l-[2-deoxy-3-0- (methylsulfonyl) - 5 - O - trityl -/3-D-threo-pentofuranosyljuracil.362 The cis relationship between the aglycon and the sulfonyloxy group precluded occurrence of intramolecular displacement. 

Compounds of the type 65 have been prepared by opening of the epoxide ring of l-(2,3-anhydro-5-0-trityl-P-D-lyxofuranosyl)uracil with a variety of carbon nucleophiles such as ethynyl lithium, vinylmagnesium bromide/cuprous iodide and l,3-dithian-2-yl lithium. These reactions afforded regioselectively 3 -C-substituted-3 -deoxy-P-D-arabinofuranosyl nucleosides 69-71 in 10-68% yield [84, 87] (Fig. 12). These intermediates have been transformed into a variety of other 3 -C-substituted-3 -deoxy-arabinofuranosyl uridines 72-77 [84]. 9-(3-Deoxy-3-C-methyl-P-D-xylofuranosyl)adenine has been prepared by glycosidation reaction of a 3-deoxy-3-C-methyl-P-D-xy/ofuranosyl chloride with adenine [90]. 

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