Stereoselective and improved syntheses and anticancer testing of 3'-O-silatranylthymidines.
A stereoselective synthesis of 3'-O-((R,R,R)-trimethylsilatranyl)thymidine (R,R,R-1) and synthesis of 3'-O-silatranylthymidine (5) via an improved silatranylation procedure using tetrakis(dimethylamino)silane are reported. Diastereomeric mixture 1 showed more activity than R,R,R-1 or 5 in a primary anticancer screen against breast, CNS, and lung cell lines; demonstrating the import of the configuration and presence, respectively, of the silatrane methyl groups for growth inhibition.
Black
Christine A
CA
Xavier University, Chemistry Department, 3800 Victory Parkway, Cincinnati, OH 45207-4221, USA.
Ucci
Jason W
JW
Vorpagel
Jeremy S
JS
Mauck
Matthew C
MC
Fenlon
Edward E
EE
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000473:pathology; D001943:Breast Neoplasms / Q000188:drug therapy / Q000473:pathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000138:chemical synthesis / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000473:pathology; D017646:Organosilicon Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D013936:Thymidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D019086:Bridged Bicyclo Compounds, Heterocyclic; D017646:Organosilicon Compounds; C015503:silatrane; D013936:Thymidine