Аннотация:We developed a conceptually novel method of β-peptides synthesis based on 1,3-cycloaddition of azomethine ylides (Figure 1).[1] Short well-defined β-proline oligomers with up to 6 monomeric pyrrolidine units were synthesized in racemic and non-racemic forms and characterized by X-ray and CD.[1,2] Some oligomeric derivatives revealed potent antiproliferative activity against hormone-refractory prostate cancer cell line PC-3.[2,3]
Figure 1. Synthesis of alternating β-proline oligomers by cycloadditive oligomerization. Reaction conditions: (i) acryloyl chloride, Et3N, CH2Cl2, 0 ˚С; (ii) R1PhCH=NCH2COR (1.0 eq), AgOAc (1.5 eq), Et3N (1.5 eq), toluene, rt. X ˗ OtBu or chiral auxiliary.
Ministry of Education and Science of the Russian Federation is acknowledged for financial support (the grant agreement number 14.578.21.0012, unique project ID RFMEFI57814X0012).
References
[1] K. V. Kudryavtsev, P. M. Ivantcova, A. V. Churakov, S. Wiedmann, B. Luy, C. Muhle-Goll, N. S. Zefirov, S. Bräse, Angew. Chem. Int. Ed. 2013, 52, 12736-12740.
[2] K. V. Kudryavtsev, P. M. Ivantcova, C. Muhle-Goll, A. V. Churakov, M. N. Sokolov, A. V. Dyuba, A. M. Arutyunyan, J. A. K. Howard, C. C. Yu, J. H. Guh, N. S. Zefirov, S. Bräse, Org. Lett. 2015, 17, 6178-6181.
[3] K. V. Kudryavtsev, C. C. Yu, P. M. Ivantcova, V. I. Polshakov, A. V. Churakov, S. Bräse, N. S. Zefirov, J. H. Guh, Chem. Asian J. 2015, 10, 383-389.