Synthesis of tryptophan-dehydrobutyrine diketopiperazines and analogues

Article abstract of DOI:10.1016/S0040-4020(98)01095-3

Condensation of N¹-methyl-cyclo-Trp-Gly and aldehydes in basic media was studied to confirm the structure of the natural product TDD (N-methyl- Tryptophan Dehydrobutyrine Diketopiperazine, 1) and to prepare analogues with potential activity as GST (Glutathione-S-Transferase) inhibitors. This strategy was successful for 1,4-diacetyl-cyclo-Trp-Gly but it did not work for N⁴-acetyl, N¹-methyl-cyclo-Trp-Gly derivatives. Pyrolytic cyclization of N-Boc-L-Thr-N-methyl-L-Trp methyl ester gave the Z-isomer of N- methyltryptophan dehydrobutyrine diketopiperazine, which was previously supposed to be the natural product. However, by comparison of melting points and pectroscopic data with those of 1, we conclude that the proposed structure for TDD must be corrected.