Potential silicon-containing antifolates

Novel silicon-containing folate derivatives were synthesized as potential i nhibitors of folate-dependent enzymes in an attempt to develop more effecti ve antitumor agents. A dimethylsilyl moiety was inserted into the sidechain of two known antifolates with the aim of improving passive transport prope rties and sidechain conformational flexibility. An efficient, convergent pa lladium-catalyzed coupling methodology was used to link known heterocycles to novel, highly functionalized vinyl and ethynyl silanes. (C) 1999 Elsevie r Science Ltd. All rights reserved.