Synthesis of the side chain cross-linked tyrosine oligomers dityrosine, trityrosine, and pulcherosine.
[reaction: see text] 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 trityrosine in good yield. Access to pulcherosine was achieved through copper-catalyzed coupling of phenylalanine-4-boronic acid and 4-O-protected dopa derivatives to give an isodityrosine derivative. Selective halogenation followed by Suzuki coupling with the potassium tyrosine-3-trifluoroborate gave protected pulcherosine. Global deprotection of the protected trityrosine and pulcherosine derivatives completed the first syntheses of the corresponding tris-alpha-amino acids.
Skaff
Ojia
O
School of Chemistry, The University of Sydney, NSW 2006, Australia.
Jolliffe
Katrina A
KA
Hutton
Craig A
CA
D014443:Tyrosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis
C101095:trityrosine; C065089:pulcherosine; D014443:Tyrosine; C007543:dityrosine