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CONFORMATIONAL ANALYSIS AND SYNTHETIC APPLICATIONS OF DEOXYNITRORIBOFURANOSES; SYNTHESIS OF ULOSENUCLEOSIDES

Mahmood, Khalid (1991) CONFORMATIONAL ANALYSIS AND SYNTHETIC APPLICATIONS OF DEOXYNITRORIBOFURANOSES; SYNTHESIS OF ULOSENUCLEOSIDES. PhD thesis, University of Karachi, Karachi.

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Abstract

A new approach to ulose-derived nucleosides is described. It is based upon a chain elongation of 1-deoxy-1-nitroaldoses, followed by activation of the nitro group as a leaving group, and introduction of a pyrimidine or purine base. Thus, the nitroaldose Y106) was prepared from Y161) by pivaloylation (-Y103), synthesis of the nitrones Y107)/Y108), which were characterized as the acetates Y109)/Y110) and transformed into the nitrones Y111)/Y112).Ozonolysis of Y111)/Y112) gave Y113)/Y114), which were acetylated to Y115)/Y116). Henry reaction of Y106) lead to Y117) and Y118), which were acetylated to Y119)/Y120). Michael addition of Y106) to acrylonitrile, and to methyl propiolate yielded the anomers Y121)/Y122), and Y123)/Y124), respectively. Similar reactions of Y115)/Y116) were prevented by a facile B-elimination. Therefore, the nitrodiol Y114) was transformed into the orthoesters Y125) and hence, by Henry reaction, patial hydrolysis, and acetylation, into Y126) and Y127). The structure of Y117) was established by X-ray analysis. It is the major product of the kinetically controlled Henry reaction of Y106). Similarly, the B-D configurated nitroladoses Y121), and Y123) are the major products of the Michael addition. This indicates a preferred endo attack on the nitronate anion derived from Y160). AMI calculations for this anion indicate a strong pyramidalization at C(1), in agreement with an endo attack. Nucleosidation of Y119) by Y129) afforded Y131) and Y130). Yields depend strongly upon the nature and the amount of the promoter, and reach 68% for Y130) which was transformed into Y134), Y135) and the known psicouridine *Y136). To probe the mechanism, the trityl protected Y128) was nucleosidated, yielding Y133), or Y133) and Y132), depending upon the amount of FeCl3. Nucleosidation kof the nitroacetate Y126) was more difficult, required SnCl2 as a promoter, and yielded Y137) and Y138). The B-d-anomer Y138) was transformed into Y136). Nucleosidation of Y121) (SnCl4) yielded the anomers Y139) and Y140), which were transformed into Y141) and Y142), and hence into Y143) and Y144). Similarly, nucleosidation of Y123) yielded Y145) and Y146) which were deprotected to Y147) and Y148), respectively. The nucleoside Y147) was saponified to Y149). Nucleosidation of Y119) by Y150) (SnCl2) afforde the purine nucleosides Y152). The purine nucleoside Y152) was deprotected (-Y153)-Y154) to psicofuranine (Y102), which was also obtained from Y156), obrained along with Y155), by nucleosidatlion of Y126). The structure, and particularly the conformation of the intradoses, nitrouloses, and of the nucleosides are examined.

Item Type:Thesis (PhD)
Uncontrolled Keywords:deoxynitroribofuranoses, ulosenucleosides, pyrimidine, nitroaldose
Subjects:Physical Sciences (f) > Chemistry(f2)
ID Code:714
Deposited By:Mr. Muhammad Asif
Deposited On:27 Sep 2006
Last Modified:04 Oct 2007 21:02

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