SYNTHESIS OF A 14-MEMBERED CYCLIC PEPTIDE MODEL OF THE CFG RINGS OF RISTOCETIN-A AND OBSERVATIONS ON ATROPDIASTEREOISOMERISM

Two routes for the synthesis of a 14-membered heterodetic cyclic pepti de as a model for the CFG ring system of the antibiotic ristocetin A ( 2) are described. The key aryl ether bonds for this molecule were cons tructed by using the reaction of phenoxides from (hydroxyaryl)glycine derivatives with tricarbonyl (3-methoxy-2-methylchlorobenzene) mangane se hexafluorophosphate (11). This coupling reaction can be performed i n the presence of protected amino acids and dipeptides without racemiz ation of the sensitive arylglycine. Stereoselective introduction of th e F-ring glycine side chain was accomplished by reaction of the aryl e ther manganese complexes with Schollkopf's bislactim glycine enolate e quivalent. The product(s) from this reaction were demetalated and arom atized by treatment with N-bromosuccinimide. Deprotection of the aroma tized compounds followed by cycloamidation furnished two atrodiastereo meric cyclic peptides corresponding to the target molecule, the struct ures of which were assigned on the basis of BD-NMR NOESY experiments c oupled with molecular modeling. One of the product molecules correspon ds closely to the structure that has been proposed for the CFG ring sy stem of proposed for the CFG ring of ristocetin, except for the orient ation of the w(3) amide group.