IMPROVED METHOD FOR DERIVATIZED SOLID PHASE RESINS

THE PREPARATION OF PEPTIDES BY SOLID PHASE METHODS USUALLY REQUIRES A RAPID, RELIABLE, AND RACEMIZATION-FREE PROCEDURE TO ATTACH THE FIRST AMINO ACID ONTO THE FUNCTIONALIZED SOLID SUPPORT. CURRENT METHODS EITHER GIVE UNACCEPTABLE LOSS OF OPTICAL PURITY OR FAIL TO GIVE HIGH ENOUGH LEVELS OF CONVERSIONS. THE LATTER PROBLEM AT BEST MEANS A LOWER YIELD OF DESIRED PRODUCT AND AT WORST LEAVES BEHIND UNDERIVATIZED FUNCTIONAL GROUPS THAT MAY INTERFERE WITH SUBSEQUENT STEPS IN THE SYNTHESIS. RECENTLY CARPINO ET AL, HAVE REPORTED THAT FMOC PROTECTED AMINO ACID FLUORIDES CAN FURNISH SUPERIOR RESULTS IN SOLID PHASE SYNTHESIS BY PROVIDING AN EXTREMELY RAPID (LESS THAN 10 MINUTES) AND RACEMIZATION-FREE COUPLING METHOD. WE WILL EXTEND THEIR REAGENTS TO THE COMMERCIAL PREPARATION OF A COMPLETE LINE OF FMOC-AMINO ACID WANG RESINS. OUR PRELIMINARY STUDIES SUGGEST THAT THE SPEED OF THE COUPLING ALSO EXTENDS TO THE INITIAL RESIN FUNCTIONALIZATION STEP THE FEASIBLITY OF THIS APPROACH WILL BE FURTHER VERIFIED BY THE USE OF VARIOUS CHROMATOGRAPHIC METHODS (TO CONFIRM THE STEREOSPECIFICITY OF THE ATTACHMENT STEP) AND BY THE PREPARATION OF FMOC-HIS(TRT)-RESINS AND FMOC-CYS(TBU)-RESINS.