Partial synthesis of five new analogues of the peptido-lactone Virginiamycine S1, modified in the fifth and/or sixth position ([Xxx5]-VS1 with Xxx = Ala, Asp, Asn and Lys and [Ala5,Gly6]-VS1).
We achieved the reconstruction of VS1-analogues containing a substitute for the fifth residue, gamma-oxo-Pip (Pip = pipecolic acid), starting from VS1-pentapeptide (VS5P;3) the latter being prepared by a two-step degradation process of the native antibiotic VS1 (1a). Protecting groups during the procedure were chosen in order to realize a minimal number of steps. Most of these gave excellent yields, including final cyclization between the fourth and fifth residue. In total, four analogues were synthesized with Ala, Asp, Asn and Lys (1b) replacing gamma-oxo-Pip. Among these, [Lys5(Tfa salt)]-VS1 is water-soluble, which is an important characteristic for eventual application of VS1 as a pharmaceutical agent. In the proposed reaction sequence, we made sure that residues 4 (MePhe) and 6 (Phg) became partially epimerised. We therefore obtained each time after cyclization a total of four epimers that have been separated by preparative TLC. The chiral identity of the final residues was realized by GC (Chirasil Val-III) on the total hydrolysates.
Moerman
M C
MC
Laboratory for Organic Chemistry, State University of Ghent, Belgium.
Anteunis
M J
MJ
D000595:Amino Acid Sequence; D009682:Magnetic Resonance Spectroscopy; D008722:Methods; D008969:Molecular Sequence Data; D015394:Molecular Structure; D013237:Stereoisomerism; D014769:Virginiamycin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry
D014769:Virginiamycin