Ibe novel dimeric amino acid isodityrosine I has been synthesized by a route which uses a new method of diil ether pqaraLia~. Nucleophilic addition of a protected tymsine to cyclohexenone oxide and the Pd(O)-catalyzed coupling of an aryl iodide with a pmteued iodoalani derivative are the key steps in thii synthesis. This represents one of the first efficient syntheses of this molecule beginning with two oat~y-occurring amino acids as inexpensive starting materials 0 1997 Elsevier Science Ltd. Isodityrosine4 (1). the key structural subunit which defines a large class of biologically active natural products was isolated in the early 1980's from extensin, a plant cell wall glycoprotein. Piperazinomycins (2a) possesses antimicrobial and antifungal activity, the cyclic tripeptide K-136 (2b) is a potent, noncompetitive inhibitor of angiotensin I converting enzyme, and OF4949-I -OF4949-IV7 (2c-I') are inhibitors of aminopeptidase B and also exhibit immunopotentiating and antitumor activity. The bicyclic hexapeptides bouvardins (2g) and deoxybouvardins (2h) are members of a large class of potent antitumor antibiotics, including RA-I -RA-IV9 (2i-I). tzLC02H 5's HO*C,*%F;aH*c NH2 ;