Serine-containing 10-membered cyclodepsipeptides. Synthesis and molecular structure of PhCH2CO-DSer-Pro-Pro- and PhCH2CO-DSer-Pro-DPro-.
As a part of a research program aimed at studying synthesis and conformation of small ring peptides, the cyclization of diastereoisomeric N-phenylacetyl-seryl-propyl-proline tripeptides has been examined. Two 10-membered peptide lactones, PhCH2CO-DSer-Pro-Pro- 5a and PhCH2CO-DSer-Pro-DPro- 5b, have been isolated by treating the corresponding linear p-nitrophenyl esters with DBU in dry benzene. In these two compounds the serine lactone fragment (a common structural feature of several bioactive cyclodepsipeptides) is inserted into a highly strained small ring system. The conformation in the crystal of 5a and 5b has been studied by X-ray analysis. Both the 10-membered rings of 5a and 5b adopt an overall cis-cis-trans conformation in which the lactone junction is trans. The deviations from planarity of the peptide units vary from delta omega = 30 degrees for the DSer-Pro bond in 5b to delta omega = 5-6 degrees for the DSer-Pro bond in 5a and Pro-DPro bond in 5b. The skeletal atoms of 5b, containing the Pro-DPro sequence, are related by a pseudo-symmetry mirror plane passing through the Pro carbonyl and the opposite DSer C beta H2 group. In both the molecules the exocyclic amide bond adopts an extended conformation with respect to the DSer-Pro ring junction; this arrangement gives rise to a C5-type ring structure which is well evidenced in the case of 5a.
Cerrini
S
S
G. Giacomello Institute of Structural Chemistry, C.N.R., Monterotondo Stazione, Rome, Italy.
Gavuzzo
E
E
Luisi
G
G
Pinnen
F
F
D000595:Amino Acid Sequence; D008958:Models, Molecular; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000737:chemistry; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry; D011487:Protein Conformation; D012694:Serine / Q000737:chemistry; D014961:X-Ray Diffraction
D009842:Oligopeptides; D010456:Peptides, Cyclic; D012694:Serine