Selective Protection of 2‘,2‘-Difluorodeoxycytidine (Gemcitabine)
- 1 October 1999
- journal article
- Published by American Chemical Society (ACS) in The Journal of Organic Chemistry
- Vol. 64 (22) , 8319-8322
- https://doi.org/10.1021/jo9911140
Abstract
Gemcitabine (1) is a promising new anticancer agent used in pancreatic cancer. Improvement in the selective targeting of compound 1 and other cytotoxic agents to solid tumors may be enhanced by conjugation to ligands that target peripheral benzodiazepine receptors (PBRs) located on mitochondria and known to be overexpressed in human brain tumors. Development of such chemical conjugates requires selective protection on 4-NH(2), 3'-OH, and 5'-OH of compound 1. All three monoprotected and three diprotected gemcitabine derivatives (2 to 7) were synthesized in good yield by employing a single commonly used protecting reagent, di-tert-butyl dicarbonate, under different conditions. Consequently, the three mono-ligand-gemcitabine conjugates coupled at 4-NH(2), 3'-OH, and 5'-OH respectively (14 to 16) were synthesized in high yield using the PBR ligand PK11195. This selective protection/deprotection strategy offers a relatively straightforward means to modify other nucleosides.Keywords
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