Solid-phase synthesis of a thymidinyl dipeptide urea library.
A thymidinyl dipeptide urea library with structural similarity to the nucleoside peptide class of antibiotics was designed and synthesized. To generate the library, a solid-phase synthesis was developed starting from 5'-azidothymidine attached to a polystyrene butyl diethylsilane (PS-DES) resin support. This study describes the prelibrary solid-phase synthesis development including maximum loading capacity optimization, selection of orthogonal functionalized side-chain protection strategies, synthesis of a 64-member test library, and optimization of the final cleavage step. Using the optimized procedures, we synthesized a 1000-member library in a 50 micromol quantity using IRORI-directed sorting technology in MiniKans, producing the target library in good yields and purity.
Sun
Dianqing
D
Department of Pharmaceutical Sciences, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.
Lee
Richard E
RE
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D019151:Peptide Library; D011137:Polystyrenes / Q000737:chemistry; D012821:Silanes / Q000737:chemistry; D013237:Stereoisomerism; D013941:Thymine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D014508:Urea / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry
D004151:Dipeptides; D019151:Peptide Library; D011137:Polystyrenes; D012821:Silanes; C520894:polystyrene butyl diethylsilane; D014508:Urea; D013941:Thymine