1235568-38-3Relevant academic research and scientific papers
Synthesis and conformational analysis of bicyclic extended dipeptide surrogates
Ranatunga, Sujeewa,Liyanage, Wathsala,Del Valle, Juan R.
experimental part, p. 5113 - 5125 (2010/10/04)
(Figure presented) Regio- and diastereoselective reactions of a homoproline enolate enable the synthesis of novel extended dipeptide surrogates. Bicyclic carbamate 9 and fused β-lactam scaffold 11 were prepared from l-pyroglutamic acid via substrate-controlled electrophilic azidation. Synthesis of orthogonally protected hexahydropyrrolizine, hexahydropyrrolizinone, and hexahydropyrroloazepinone dipeptide surrogates relied on allylation of proline derivative 5, followed by Curtius rearrangement to introduce the N-terminal carbamate group. A total of six azabicycloalkane derivatives were evaluated for conformational mimicry of extended dipeptides by a combination of X-ray diffraction and molecular modeling. Analysis of putative backbone dihedral angles and N- to C-terminal dipeptide distances indicate that compounds (α′S)-14b and 21 approximate the conformation of dipeptides found in β-sheets, while tripeptide mimic 28 is also highly extended in the solid state. Structural data suggest that ring size and relative stereochemistry have a profound effect on the ability of these scaffolds to act as β-strand mimetics and should inform the design of related conformational probes.
