Stereocontrolled routes to β,β′-disubstituted α-amino acids

Abstract

Owing to their significant abundance in natural products, chiral beta,beta'-disubstituted alpha-amino acids remain an important synthetic objective. Emphasis has been focused in this critical review on the great diversity of enantio- and diastereoselective methodologies to reach these highly functionalized compounds. The oldest and cutting edge synthetic methods are described in parallel with the synthesis of many relevant biologically active targets (224 references).

A Convenient Method for Preparation of α-Imino Carboxylic Acid Derivatives and Application to the Asymmetric Synthesis of Unnatural α-Amino Acid Derivative

“…For column chromatography, silica gel (KANTO KAGAKU N-60) was employed. NMR spectra were recorded using a Bruker AV400N at 400 MHz frequency or JEOL JNM-AL300 for 1 H, and JEOL JNM-AL300 at 75 MHz frequency for 13 C in the stated solvents using tetramethylsilane as an internal standard. Chemical shifts were reported in parts per million (ppm) on the δ scale from an internal standard (NMR descriptions: s, singlet; d, doublet; t, triplet; q, quartet; hept, heptet; m, multiplet; br, broad).…”

“…[7][8][9][10][11] These contexts evoke much interest of synthetic chemists in asymmetric synthesis of the structural unit. 12,13) Enabling easy access to diverse α-amino acids only by changing nucleophiles employed, Mannich-type reaction of α-imino ester has been widely utilized for the asymmetric synthesis. [14][15][16][17][18][19][20] Generally, condensation of glyoxalates and primary amines affords α-imino esters as the requisite substrate for Mannich-type reaction (Chart 1a); however, the glyoxalates are unstable, and suffer easy hydrolysis or polymerization at room temperature.…”

Nitroalkanes as Key Compounds for the Synthesis of Amino Derivatives

“…The tremendous importance that -amino acids hold as biologically active substances is indisputable and is witnessed by the very large number of synthetic procedures available for their preparation [52]. Regarding the chemistry of the nitro group, the most viable strategy to prepare open chain -amino acids consists in the utilization of nitroacetate esters 77.…”

Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

“…Classical approaches continue to be investigated (most notably the Strecker reaction) [2], but recent developments focus on cycloadditions [3], rare amino acids [4], chiral catalysis [5], etc. It is noteworthy, however, that two of the most widely applied methods for the introduction of the amine group – the Beckmann [6–9] and the Hofmann [10–13] rearrangements – are not represented in these approaches.…”