Synthesis of the side chain cross-linked tyrosine oligomers dityrosine, trityrosine, and pulcherosine

Abstract

An efficient synthesis of dityrosine and the first syntheses of the tyrosine trimers trityrosine and pulcherosine have been achieved. Protected 3-iodotyrosine underwent tandem Miyaura borylation-Suzuki coupling to give protected dityrosine. The choice of benzyl carbamate, ester, and ether protecting groups enabled a one-step global deprotection to give dityrosine. Suzuki coupling of protected 3,5-diiodotyrosine and tyrosine-3-boronic acid derivatives gave the corresponding trityrosine, but in low yield. However, use of a potassium tyrosine-3-trifluoroborate derivative in place of the corresponding pinacol boronate ester, in combination with protecting group variation, gave protected trityros..