Solid-phase synthesis of linear ureas tethered to hydantoins and thiohydantoins.
An efficient method for the solid-phase synthesis of hydantoins and thiohydantoins tethered to ureas, starting from a resin-bound amino acid, is presented. Following reduction of the amide with borane-THF, a second amino acid was selectively coupled to the primary amine followed by treatment of the secondary amine by an isocyanate to generate the corresponding urea. Hydantoin and thiohydantoin formation was achieved through the use of carbonyldiimidazole and thiocarbonyldiimidazole, respectively. Cleavage from the solid support using hydrogen fluoride, followed by extraction and lyophilization, provided the desired urea-linked heterocyclic compounds in good yield and high purity.
Nefzi
Adel
A
Torrey Pines Institute for Molecular Studies, 3550 General Atomics Court, San Diego, California 92121, USA.
Giulianotti
Marcello
M
Truong
Long
L
Rattan
Somkit
S
Ostresh
John M
JM
Houghten
Richard A
RA
D020650:Combinatorial Chemistry Techniques; D006827:Hydantoins / Q000138:chemical synthesis*; D013867:Thiohydantoins / Q000138:chemical synthesis*; D014508:Urea / Q000031:analogs & derivatives*
D006827:Hydantoins; D013867:Thiohydantoins; D014508:Urea