WE ARE EXPLORING SYNTHETIC ROUTES TOWARD THE SYNTHESIS OF AMINO ACIDS WHICH CONTAIN EITHER A SELENIUM OR TELLURIUM ATOM. CURRENT TARGETS ARE TE AND SE LABELED METHIONINE, TRYPTOPHAN, CYSTINE, AND CYSTEINE. THESE DERIVATIVES, WHEN INCORPORATED INTO BIOMACROMOLECULES, CAN ACT AS A RATIONAL HEAVY ATOM DERIVATIVE FOR X-RAY DIFFRACTION STUDIES AND AS NOVEL NMR PROBES. THE IODOALANINE IS CONVENIENTLY CONSTRUCTED. THE SYNTHESIS CAN BE CARRIED OUT IN BULK AND HAS BEEN REPORTED TO OCCUR WITHOUT RACEMIZATION. THE IODOALANINE USUALLY NEEDS TO BE FRESHLY CRYSTALLIZED BEFORE USE. RACEMIC SELENOCYSTINE HAS BEEN CONSTRUCTED USING CHLOROALANINE AND DISODIUM DISELENIDE IN A 27% YIELD BASED ON SELENIUM. SINCE THE COST OF 92% ENRICHED 77SE IS 20-30$/MG AND ~500 MG OF THE RACEMIC AMINO ACID WILL BE NEEDED FOR BIOINCORPORATION, WE HAVE DEVELOPED A MORE EFFICIENT ROUTE USING IODOALANINE. TREATMENT OF SELENIUM WITH SUPER HYDRIDE GIVES THE DILITHIODISELENIDE. THE SOLUTION WAS CHILLED TO -78OC AND THE IODOALANINE WAS ADDED. THE PROTECTED SELENOCYSTINE WAS ISOLATED IN 85% YIELD. REPEATING THE ABOVE PROTOCOL WITH SUBLIMED 92% 77SE GAVE A 90% YIELD OF THE AMINO ACID. HYDROLYSIS WITH 2.0 EQUIVALENTS OF LIOH AFFORDED THE DIACID. INITIAL RESULTS FROM COUPLING OF THE DIACID TO THE CHIRAL SELONE NMR REAGENT, FOLLOWED ANALYSIS BY 77SE NMR SPECTROSCOPY, HAVE INDICATED THAT THE ENANTIOMERIC EXCESS IS GREATER THAN 97%. CLEAVAGE OF THE BENZYL ESTER WITH LIOH FOLLOWED BY IN SITU DEPROTECTION OF THE BOC PROTECTING PROTECTING GROUP WITH TRIFLUOROACETIC ACID GIVES THE AMINO ACID.
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