I= STUDIES OF THE ALKYLATION OF CYTIDINE AND URIDINE NUCLEOTIDES UNDER STRONGLY ALKALINE CONDITIONS
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Title of Thesis
STUDIES OF THE ALKYLATION OF CYTIDINE AND URIDINE NUCLEOTIDES UNDER STRONGLY ALKALINE CONDITIONS

Author(s)
M. Qudart-e-Khuda
Institute/University/Department Details
Department of Biochemistry/ University of Karachi
Session
1991
Subject
Biochemistry
Number of Pages
201
Keywords (Extracted from title, table of contents and abstract of thesis)
cytidine nucleotides, uridine nucleotides, alkylation, phosphate groups, amino groups, ring nitrogens, keto groups, nucleoside analogues, cyclic nucleotides

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 5’MP 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’ –O-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’UMP; 3’-0-allyluridine 5-monophosphate allylester, 2-O-allyl 5’-UMP and 3’-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.

Download Full Thesis
1292.91 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents
93.34 KB
2 1 Introduction 1
55.51 KB
3 2 Nucleoside Analogues 7
114.64 KB
  2.1 Clinically Important Synthetic Base Analogues 9
  2.2 Nucleosides With Modifications In Heterocyclic Base Moiety 11
  2.3 5-Substitued Pyrimidine Deoxyriosides 11
  2.4 Cytosie Arbinosides 11
  2.5 Clinically Important Nucleoside Analogues 15
  2.6 Miscellaneous Biologically Active Nucleosides 17
  2.7 Nucleosides With Modification In Sugar And Heterocyclic Base Moiety 20
4 3 Nucleotides 21
241.4 KB
  3.1 Cyclic Nucleotides 26
  3.2 Synthesis Of Nucleotides 27
  3.3 Physical Properties Of Nucleotides 30
  3.4 Conformation Of Nucleotides 32
  3.5 Chemical Reactions Of Nucleotides 33
5 4 2- Alkyl Purine Nucleotides 59
31.71 KB
6 5 6-Substituted Pyrimidine Nucleotides 64
11.32 KB
7 6 Alkylation Of Nucleosides And Nucleotides 64
45.25 KB
8 7 Results And Discussions 71
595.8 KB
  7.1 Reaction Of 5’-CMP With Methyliodide 82
  7.2 Reaction Of 5’-CMP With Ethyliodide 88
  7.3 Reaction Of 5’-CMP With N- Propyliodide 96
  7.4 Reaction Of 5’-CMP With Propyliodide 102
  7.5 Reaction Of 5’-CMP With Allylchloride 104
  7.6 Reaction Of 5’-CMP With Methyliodide 117
  7.7 Reaction Of 5’-CMP With Ethyliodide 122
  7.8 Reaction Of 5’-CMP With Iso-Propyliodide 1130
  7.9 Reaction Of 5’-CMP With N- Propyliodide 133
  7.10 Reaction Of 5’-CMP With Allylchloride 136
9 8 Experimental 151
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  8.1 Alkylation Of Cytidine 5’- Monophosphate( 5’-CMP) With Methyliodide 158
  8.2 Alkylation Of Cytidine 5’- Monophosphate( 5’-CMP) With Ethyliodide 161
  8.3 Alkylation Of Cytidine 5’- Monophosphate( 5’-CMP) With N- Propyliodide 163
  8.4 Alkylation Of Cytidine 5’- Monophosphate( 5’-CMP) With Iso-Propyliodide 166
  8.5 Alkylation Of Cytidine 5’- Monophosphate( 5’-CMP) With Allylchloride 167
  8.6 Alkylation Of Uridine 5’- Monophosphate( 5’-UMP) With Methyliodide 171
  8.7 Alkylation Of Uridine 5’- Monophosphate( 5’-UMP) With Ethyliodide 172
  8.8 Alkylation Of Uridine 5’- Monophosphate( 5’-UMP) With Iso-Propyliodide 175
  8.9 Alkylation Of Uridine 5’- Monophosphate( 5’-UMP) With N- Propyliodide 177
  8.10 Alkylation Of Uridine 5’- Monophosphate( 5’-UMP) With Allylchloride 179
10 9 References 183
127.28 KB