Département de Chimie, Université de Montréal, C.P. 6128 Succursale Centre-Ville, Montreal, QC H3C 3J7, Canada.
Molecules. 2021 Dec 23;27(1):67. doi: 10.3390/molecules27010067.
The constrained dipeptide surrogates 5- and 7-hydroxy indolizidin-2-one -(Boc)amino acids have been synthesized from L-serine as a chiral educt. A linear precursor ∆-unsaturated (2,8)-2,8-bis[-(Boc)amino]azelic acid was prepared in five steps from L-serine. Although epoxidation and dihydroxylation pathways gave mixtures of hydroxy indolizidin-2-one diastereomers, iodolactonization of the ∆-azelate stereoselectively delivered a lactone iodide from which separable (5)- and (7)-hydroxy indolizidin-2-one -(Boc)amino esters were synthesized by sequences featuring intramolecular iodide displacement and lactam formation. X-ray analysis of the (7)-hydroxy indolizidin-2-one -(Boc)amino ester indicated that the backbone dihedral angles embedded in the bicyclic ring system resembled those of the central residues of an ideal type II' β-turn indicating the potential for peptide mimicry.
已经从 L-丝氨酸合成了受约束的二肽替代物 5-和 7-羟基吲哚里西啶-2-酮-（Boc）氨基酸。从 L-丝氨酸出发，通过五步反应制备了线性前体 ∆-不饱和（2,8）-2,8-双[（Boc）氨基]庚酸。尽管环氧化和二羟基化途径得到了羟基吲哚里西啶-2-酮非对映异构体的混合物，但 ∆-庚酸的碘内酯化立体选择性地提供了内酯碘化盐，可通过特征为分子内碘取代和内酰胺形成的序列来合成可分离的（5）-和（7）-羟基吲哚里西啶-2-酮-（Boc）氨基酯。（7）-羟基吲哚里西啶-2-酮-（Boc）氨基酯的 X 射线分析表明，双环环系统中嵌入的主链二面角类似于理想的 II'β-转角的中心残基的二面角，表明具有肽模拟的潜力。
