Synthesis and Cytostatic Activities of New 6-Substituted Purinylcarbonucleosides Derived from Indan [1]

Abstract

A new series of 6-substituted purinylcarbonucleosides derivatives of indan, 8a-g and 10a-d, was synthesized from (±)-cis-1,3-indandimethanol acetate (5), which was prepared in three steps from benzonorbornadiene. 6-Chloropurine was introduced both by Mitsunobu reaction with 5 and by substitution of the mesylate 6. Suzuki-Miyaura reactions of the protected 6-chloropurine derivative 7 with substituted phenylboronic acids afforded 9a-d (protected purine derivatives with substituted phenyl rings at position 6); deprotection of the latter yielded the new series of purinylcarbonucleoside indan derivatives 10a-d. Treatment of compound 7 with R′H/NaOH afforded a parallel series 8a-g, with alkoxy or amino groups R′ at position 6 instead of substituted phenyl rings.

Key words

synthesis - antineoplastic agent - indan carbocyclic nucleoside - Mitsunobu reaction - Suzuki-Miyaura cross-coupling reaction

1

Part of this work was presented at the XIV International Round Table on Nucleosides, Nucleotides and their Biological Applications, San Francisco, USA, September 2000 and XII Congreso Nacional de la Sociedad Española de Química Terapéutica, Sevilla, Spain, September 2001.

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1

Part of this work was presented at the XIV International Round Table on Nucleosides, Nucleotides and their Biological Applications, San Francisco, USA, September 2000 and XII Congreso Nacional de la Sociedad Española de Química Terapéutica, Sevilla, Spain, September 2001.