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Guo ZW , Gallo JM
Selective Protection of 2',2'-Difluorodeoxycytidine (Gemcitabine)
J Org Chem. 1999 Oct 29;64(22) :8319-8322
PMID: 11674754 URL: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=11674754
AbstractGemcitabine (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.
Notes0022-3263 Journal article