Semisynthesis of DB-67 and other silatecans from camptothecin by thiol-promoted addition of silyl radicals.
Thiol- or acid-promoted additions of silyl radicals to camptothecin are reported. At 105 degrees C, mixtures of 7-silyl (favored) and 12-silyl camptothecins are formed alongside substantial amounts of recovered camptothecin. At 160 degrees C, 12-silyl isomers are formed preferentially, but the total mass balance is substantially reduced. The silyl radical addition is featured in short semi-syntheses of DB-67 (7-tert-butyldimethylsilyl-10-hydroxy camptothecin) from both camptothecin and 10-hydroxycamptothecin.
Du
Wu
W
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Kaskar
Bashir
B
Blumbergs
Peter
P
Subramanian
P-K
PK
Curran
Dennis P
DP
D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry*; D005609:Free Radicals / Q000737:chemistry; D006358:Hot Temperature; D007536:Isomerism; D017646:Organosilicon Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis / Q000737:chemistry*
D005609:Free Radicals; D017646:Organosilicon Compounds; D013438:Sulfhydryl Compounds; C415575:7-tert-butyldimethylsilyl-10-hydroxycamptothecin; D002166:Camptothecin