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KMID : 0617320020110010305
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Journal of Pharmacetical Sceiences Ewha Womans University
2002 Volume.11 No. 1 p.305 ~ p.313
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Synthesis and Biological Evaluation of Novel Thioapio Dideoxynucleosides
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Moon, Hyung Ryong
Kim, Hea Ok/Lee, Sang Kook/Choi, Won Jun/Chun, Moon Woo/Jeong, Lak Shin
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Abstract
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On the basis of the bioisosteric rationale to apio dideoxynucleosides. novel thioapio dideoxynucleosides have been syn-thesized, starting from 1,3-dihydroxyacetone via thioapio sugar acetate 6 as a key intermediate. The intermediate 6 was condensedwith silylated pyrimidine bases such as N^4-benzoylcytosine, uracil or thymine inl the presence of TMSOTf to give the β-anomers (8a,1la, and 12a) and α-anomers (8b, llb, and 12b), respectively. The intermediate 6 was also condensed with silyiated 6-chloropurineto give the 6-chloropurine derlvatives 14a and 14b which were converted to adenine derivatives 15a and 15b, N^6-methyladeninederivatives 16a and 16b, and hypoxanthine derivatives 17a and 17b. respectively. The guanine analogues 20a and 20b were alsosynthesiaed from the condensation of sugar acetate 6 with 2-acetamido-6-chlororurine . All synthesized fina1 compound swere testedaSainst HIV-1. Most of the synthesized compounds exhibited toxiclty-dependent anti-HIV-1 activity, among which 6-chloropurinederivative 14b was found to be the most cytotoxic and showed good cytotoxicity against colon cancer ceil lines. Although we couldnot find good anti-HIV agents in this study, findings of some anticancer activity in this series will allow this class of nucleosides tobe the new template for the development of new anticancer agents (Fig. 1).
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KEYWORD
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