School of Chemistry, University of Manchester , Oxford Road, Manchester M13 9PL, U.K.
J Org Chem. 2014 May 16;79(10):4659-75. doi: 10.1021/jo500714b. Epub 2014 Apr 24.
Oligomers of α-aminoisobutyric acid (Aib) are achiral peptides that typically adopt 310 helical conformations in which enantiomeric left- and right-handed conformers are, necessarily, equally populated. Incorporating a single protected chiral residue at the N-terminus of the peptide leads to induction of a screw-sense preference in the helical chain, which may be quantified (in the form of "helical excess") by NMR spectroscopy. Variation of this residue and its N-terminal protecting group leads to the conclusion that maximal levels of screw-sense preference are induced by bulky chiral tertiary amino acids carrying amide protecting groups or by chiral quaternary amino acids carrying carbamate protecting groups. Tertiary L-amino acids at the N-terminus of the oligomer induce a left-handed screw sense, while quaternary L-amino acids induce a right-handed screw sense. A screw-sense preference may also be induced from the second position of the chain, weakly by tertiary amino acids, and much more powerfully by quaternary amino acids. In this position, the L enantiomers of both families induce a right-handed screw sense. Maximal, and essentially quantitative, control is induced by an L-α-methylvaline residue at both positions 1 and 2 of the chain, carrying an N-terminal carbamate protecting group.
α-氨基异丁酸（Aib）的低聚物是手性无规肽，通常在 310 螺旋构象中采取无规卷曲，其中对映体的左、右手性构象必然是等量的。在肽的 N 末端引入一个保护的手性残基，会导致螺旋链中诱导出螺旋手性偏好，这可以通过 NMR 光谱来定量（以“螺旋过剩”的形式）。通过改变这个残基及其 N 末端保护基，可以得出结论，最大程度的螺旋手性偏好是由带有酰胺保护基的大体积手性叔氨基酸或带有氨基甲酸酯保护基的手性季铵酸诱导的。低聚物 N 末端的叔 L-氨基酸诱导出左旋螺旋手性，而季 L-氨基酸诱导出右旋螺旋手性。螺旋手性偏好也可以从链的第二个位置诱导，叔氨基酸的诱导作用较弱，而季铵酸的诱导作用要强得多。在这个位置，两种氨基酸家族的 L 对映体都诱导出右旋螺旋手性。通过在链的第 1 位和第 2 位都使用带有 N 末端氨基甲酸酯保护基的 L-α-甲基缬氨酸残基，可以诱导出最大的、几乎定量的控制。
