Synthesis of Protected L,L-Cyclotryptophyltyrosine, a Key Unit of Tryptorubin A

A protected form of L,L-cyclotryptophyltyrosine, a key structure of the bicyclic hexapeptide tryptorubin A isolated from Streptomyces sp. CLI2509, was synthesized. Treatment of Boc-L-Trp-3-borono-L-Tyr(Me)-OMe, obtained from the coupling reaction of Boc-L-Trp-OH and H2N-3-iodo-L-Tyr(Me)-OMe and the subsequent borylation of iodide, with Cu(OAc)2, pyridine, and 4 Å molecular sieves in dichloromethane at 30 °C for 48 h at a concentration of 0.001 M gave protected L,L-cyclotryptophyltyrosine in 58% yield. The structure of obtained protected L,L-cyclotryptophyltyrosine was confirmed by X-ray crystallography, revealing the presence of a pyramidal indole nitrogen atom.