Synthesis of enantiomerically enriched (R)-¹³C-labelled 2-aminoisobutyric acid (Aib) by conformational memory in the alkylation of a derivative of L-alanine

Abstract

SummaryThe method of Kouklovsky and coworkers for the enantioselective alkylation of cyclic N-naphthoyl derivatives of amino acids was used to introduce a 13C label into one of the two enantiotopic methyl groups of 2-aminoisobutyric acid (Aib) by retentive alkylation of L-alanine with 13CH3I. Conditions were identified for optimization of yield and enantiomeric purity, and the absolute configuration of the labelled product was established.

Induction of Unexpected Left‐Handed Helicity by an N‐Terminal L‐Amino Acid in an Otherwise Achiral Peptide Chain

“…Achiral tetramers of Aib were made as their N-terminal azide and C-terminal tert-butyl ester, N 3 Aib 4 OtBu (1), [10] and coupled at their C terminus with either GlyNH 2 to give 2 or with enantiomerically enriched mono-13 C-labeled (R)-Aib* [19] to give 3 (Scheme 1). After reduction of the N-terminal azide, ligation of 2 or 3 with a selection of Cbz-protected l-amino acids gave the sets of compounds 4 and 7 shown in Scheme 1.…”

Synthesis of new, optically active 1-(substituted aryl)pyrrole derivatives via atropisomerism directed diastereoselective metalation

“…These experimental results may be rationalised if one take into consideration that esterification is governed by the acidity difference of the two carboxylic groups while basic hydrolysis occurs more easily on the sterically less hindered site of the molecule. In order to determine the exact structure of (R a ,S)-(+)-9a, two dimensional 1 H, 13 C-HMBC spectroscopic measurements were performed. These measurements confirmed without doubt that the ethoxycarbonyl group is connected to the carbon atom of the benzylic -CH(CH 3 )-group.…”

“…10 In the last decade Clayden published numerous articles on the behaviour and diastereoselective reactions of benzamide derivatives having atropisomeric character. [11][12][13][14] Efficient intramolecular control of enantioselectivity by atropisomeric remote amide conformation has also been studied in SmI 2 -mediated reductive coupling of aldehydes with the crotonates possessing different 2-substituted 8-methoxy-1-naphthamides. 15 Recent developments in the field of intramolecular remote control of stereogenic center(s) formation using asymmetric center or atropisomeric benzamide containing compounds have also been reviewed.…”

Refoldable Foldamers: Global Conformational Switching by Deletion or Insertion of a Single Hydrogen Bond

“…The C terminal hydrogen bond of the Ala residue was “erased” chemically by functionalisation as a tertiary amide derivative using the photosensitive 5‐bromo‐7‐nitroindoline (Bni) 1 ,36 which was ligated to l ‐alanine without racemisation37, 38 to give 2 as a coupling partner. Alaninamide 2 was coupled to an Aib pentamer 3 in which the N terminal residue was enantioselectively isotopically enriched with 13 C in its pro‐ R and pro‐ S methyl groups in a 75:25 ratio,39 giving the helical25 oligomer 4 . …”