Method for making a prenyl group-substituted tyrosine compound

A method for making a prenyl group-substituted tyrosine compound of formula (I)

• a pharmaceutically acceptable salt, solvate, tautomer, stereoisomer or combination thereof;
• wherein R1 is an optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted aryl;
• R2 is —OH, —NH2, OR6, —NHR6, or —NR6R6;
• R3 is —H, —R6, —COR6, —COOR6, or —SO2R6;
• R4 and R5 are independently —H, —OH, —NH2, —OR6, —NHR6, —NR6R6;
• each R6 is independently an optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted aryl;
• R7 and R8 are independently optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted aryl;
• the method comprising:
• rearranging, in an uncatalyzed intramolecular sigmatropic rearrangement, an O-allylated tyrosine-based compound of the formula
• to form a rearranged tyrosine-based compound having an allyl group and a phenolic hydroxyl group of the formula
• reacting the phenolic hydroxyl group of the rearranged tyrosine-based compound with acetic anhydride;
• then
• olefin cross metathesizing the allyl group with an alkene in the presence of a metal complex catalyst to form the prenyl group-substituted tyrosine compound of formula (I).