Synthesis and conformation studies of rubiyunnanin B analogs

Five new analogs 4-8 of rubiyunnanin B (1), mainly modified on the tetrapeptide subunit, were synthesized. These agents 4-8 were substituted D-Ala-L-Ala-L-Tyr(OMe)-L-Ala, D-Ala-L-Ala-L-Phe-L-Ala, D-Ala-L-Ala-L-Tyr-L-Ala, D-Ala-L-Ala-L-Pro-L-Ala, and D-Ala-L-Ala-L-Ala for the D-Ala-L-Ala-c-N-Me-Tyr(OMe)-L-Ala tetrapeptide subunit. Unlike the natural product, the synthetic agents 4-8 adopt only a single solution conformation, and the central peptide bond in the cyclodityrosine subunit of compounds 4-8 adopt trans stereochemistry. Cytotoxic activities of analogs 4-8 against three human cancer cell lines including A549, BGC-823, and HeLa were evaluated and all the five synthesized peptides exhibited no effects against the test cell lines. These compounds were also evaluated for their antiinsulin resistance and insulin sensitizing activities and none of them showed activity in these assays. (C) 2014 Elsevier Ltd. All rights reserved.