Highly Efficient Stereoconservative Amidation and Deamidation of α-Amino Acids

Abstract

[reaction: see text] An overall stereoconservative protection and deprotection method of amino and carboxyl groups is presented. N-Phthaloyl N'-alkyl secondary amides of alpha-amino acids can be generated from corresponding N-phthaloyl amino acids by coupling reaction of N-alkylamines using mixed anhydride method. These secondary amides can be transformed by thermal rearrangement of intermediate nitrosoamides to O-alkyl esters with retention of configuration and excellent yields.

Asymmetric Synthesis of γ‐Fluorinated α‐Amino Acid Derivatives

“…Then the deamidation reaction was carried out by thermal decomposition of the in situ generated NЈ-nitrosoamide in a stereoconservative reaction to give the methyl ester (S)-7 in 91% yield. [46] In due course the enantiopure NЈ-methylamides 4a and 4b will be used in peptide synthesis. [44] The fluorovinyl group in compounds 2a and 2b was also stable under stronger aqueous basic conditions but hydrolysis to 4-oxonorvalines occurred under stronger aqueous acidic conditions.…”

Strain Promoted Click Chemistry of 8-Azidopurine and 5-Azidopyrimidine Nucleosides and Nucleotides with Cyclooctynes and Applications to Living Cell Imaging

“…to afford amide 324. The tert-Butyloxycarbonyl (Boc) protection on the amino group was easily deprotected using a mixture of trifluoroacetic acid and dichloromethane at ambient temperature; 312 however, deprotection of the S-trityl group was unsuccessful and led to significant glycosidic bond cleavage. Furthermore, staining of a TLC of the reaction mixture with Ellman's reagent, a stain used to visualize free thiol groups, showed no yellow color, thus proving that no free thiol was present.…”

A Simple Organocatalytic Enantioselective Synthesis of Pregabalin

“…For the purposes of the ee determination after crystallization, the amine was Boc-protected and the acid converted into the N-methyl amide. [20] N-Boc Protection of Free Amino Acid 1: NaHCO 3 (791 mg, 9.42 mmol) and Boc 2 O (822 mg, 3.77 mmol) were added consecutively at 0°C to a solution of the free amino acid 1 (crystallized from 30 % 2-propanol in water, 500 mg, 3.14 mmol) in a 1:1 mixture of THF/H 2 O (20 mL). After 30 min, the white suspension was stirred at room temp.…”