Synthesis, crystal structure and conformation in solution of four stereoisomeric cyclo-lanthionine derivatives.

Abstract

The synthesis of the four stereoisomeric cyclo-lanthionine derivatives: [formula: see text] (where AlaL denotes one end of the lanthionine unit) was carried out on a Kaiser-oxime resin starting from orthogonally protected lanthionine units. The peptide ring was prepared in 79-85% yield via amide bond formation by utilizing the method of peptide cyclization on an oxime resin (PCOR). The crystal and molecular structures of the protected cyclic dipeptides have been determined by X-ray diffraction techniques. The two cyclic lanthionine derivatives with chiralities of [R,S] and [S,R] crystallized in the orthorhombic space group P2(1)2(1)2(1) and the [R,R]- and [S,S]-cyclo-lanthionine derivatives in the monoclinic space group C2. The structures were solved by direct methods and refined to an R factor of 0.0368-0.0573. The ring amide bonds in all four compounds are cis, while the urethane group is trans and extended. The NMR spectra of the four stereoisomers in DMSO-d6 were used to determine their conformation in solution. The analysis of the NMR data with constrained distance geometry search showed the same conformational features in solution as in the crystalline state.