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STUDIES OF THE ALKYLATION OF CYTIDINE AND URIDINE NUCLEOTIDES UNDER STRONGLY ALKALINE CONDITIONS

Muhammad, Qudart-e-Khuda (1991) STUDIES OF THE ALKYLATION OF CYTIDINE AND URIDINE NUCLEOTIDES UNDER STRONGLY ALKALINE CONDITIONS. PhD thesis, University of Karachi, Karachi.

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Abstract

The pyrimidine nucleotides viz 5-CMP and 5-UMP were alkylated with various ethyliodide, normal-and chloride under strongly alkylating agents iso-propyliodides such as methyliodide, and unsaturated allylalkaline conditions. The products formed showed that the alkylation occurred predominantly on the ribose moiety of the nucleotides. When 5MP was reacted with methyliodide it gave N3-rnethyl 5-CMP;2,3-di-O-methyl 5-CMP; 2-Omethyl 5-CMP and 3-O-methyl 5-CMP derivatives. Reaction of 5-CMP .with ethyliodide gave three new products namely 2,3-di-O-ethyl 5'-CMP; 3-O-ethyl 5-CMP and 2'-O-ethyl 5-CMP derivatives. Reaction of 5-CMP with n-propyliodide resulted in the formation of N3-2-di-n-propyl 5-CMP, 2 -O-n-propyl 5 -CMP and N3-n-propyl 5 -CMP. Contrary to this the reaction of 5 -CMP with iso-propyliodide formed only one product i, e 3-Q-iso-propyl 5-CMP. The reaction of 5-CMP with Allylchloride also gave new products namely cytidine 5-monophosphate allylester, 2,3-di-O-allyl 5-CMP, 2-O-allyl 5-CMP, and 3'-O-allyl 5-CMP. Reaction of 5-UMP with the same alkylating agents as described above for 5-CMP also resulted in the formation of new products. Thus, with methyliodide it formed 2,3-diQ-methyl 5'-UMP; 2-O-methyl 5-UMP, and 3-O-methyl 5-UMP. The reaction with ethyliodide yielded 2,3-di-O-ethyl 5-UMP, 3-Q;-ethyl 5-UMP and 2-O-ethyl 5-UMP. The 5-UMP was also made to react with iso-propyliodide which resulted into two new products namely uridine 5-monophosphate iso-propyl ester, and 3 -O-iso-propyl 5-UMP. The reaction with n-propyliodide also gave two new products such as 2,3 -di-O-n-propyl 5-UMP and 2-O-n-propyl resulted in 5-UMP. The reaction of 5-UMP with Allylchloride the formation of four products namely 2,3-di-O-allyl 5; 3-0-allyluridine 5-monophosphate allylester, 2-O-allyl 5-UMP and -O-allyl 5-UMP. The new alkylated nucleotides of 5-CMP and 5 -UMP are characterized by their U. V. and 1H-NMR spectra, paper electrophoresis and Fast Atom Bombardment (FAB) mass spectroscopy. The Rf values in three different solvent systems are also reported. The U.V. spectra of the compounds at pH (2.0) and pH (12.0) together with their extinction coefficients and optical density ratios at 250/260 and 280/260 Are also reported. The studies reported in the thesis indicate that under strongly alkaline conditions the alkylation predominantly occurs at ribose hydroxyls of 5-CMP and 5-UMP while it is minimum at other centres of equal reactivity e.g. phosphate groups, amino groups, ring nitrogens and the keto groups of CMP and UMP. These studies also indicate that among the monoalkylated derivatives the syntheses of 2-O-alkylated derivatives occur in maximum yield indicating a greater stabilization of 3-OH. .Oanion under strongly alkaline conditions, The iso-propylation reaction is interesting as only the 3-O-iso-propyl derivative is obtained in case of 5-CMP; while in case of 5-UMP in addition to 3-O derivative an iso-propylester is also obtained. This points to steric hindrance offered to bulkier iso-propyl group by the base at the 2-O-position, while the 3-O-position of ribose is relatively free for the reaction to occur.

Item Type:Thesis (PhD)
Uncontrolled Keywords:cytidine nucleotides, uridine nucleotides, alkylation, phosphate groups, amino groups, ring nitrogens, keto groups, nucleoside analogues, cyclic nucleotides
Subjects:Physical Sciences (f) > Chemistry(f2) > Biochemistry(f2.1)
ID Code:1061
Deposited By:Mr. Muhammad Asif
Deposited On:19 Dec 2006
Last Modified:04 Oct 2007 21:04

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