Abstract
The synthetic potential of a novel precursor of 2,6-diaminopurine CDK inhibitors, 2-(benzylsulfanyl)-6-chloro-9-isopropylpurine, is described. The Traube purine synthesis was chosen to prepare the required 2-(benzylsulfanyl)hypoxanthine intermediate. Attempts to prepare its purin-6-yl methanesulfonic ester analogue failed. Conversion to the 6-chloropurine derivative enabled the introduction of arylamines in the presence of catalytic amounts of acid. Further chemical variety was introduced on the purine through a regioselective Mitsunobu N-9 alkylation. Oxidative cleavage of the 2(benzylsulfanyl) leaving group with an aliphatic amine was implemented as previously reported. Purvalanol A, a potent CDK inhibitor, was synthesised using this methodology. The template and intermediates were fully characterised by modern spectroscopic techniques and single-crystal X-ray diffraction. ((C) Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005).
Original language | English |
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Pages (from-to) | 939-947 |
Number of pages | 9 |
Journal | European Journal of Organic Chemistry |
DOIs | |
Publication status | Published - 25 Feb 2005 |
Keywords
- antitumor agents
- enzymes
- inhibitors
- nitrogen heterocycles
- template synthesis
- SOLID-PHASE SYNTHESIS
- IN-VITRO EVALUATION
- 2,6,9-TRISUBSTITUTED PURINES
- CELL-CYCLE
- DERIVATIVES
- DESIGN
- POTENT