Brønsted Acid-Catalyzed Epimerization-Free Preparation of Dual-Protected Amino Acid Derivatives

Abstract

An organocatalytic protocol, employing the commercially available EDC as coupling agent, has been developed for the preparation of dual-protected amino acid derivatives without epimerization. This methodology was then applied to different Boc-amino acid and amine derivatives in moderate to excellent isolated yields. In addition, racemization-free Boc deprotection was also demonstrated. Mechanism investigation through electrospray ionization (+)-mass spectrometry/mass spectrometry revealed an acyclic intermediate (no azlactone formation) activated by the camphorsulfonic acid as an organocatalyst as a key step for the sequential attack of the nucleophile.

Dual‐protected amino acid derivatives as new antitubercular agents

“…Analytical TLC was performed on TLC plates (silica gel 60F254) and visualized employing a ninhydrin (2,2‐dihydroxyindane‐1,3‐dione) indicator. All the tested compounds had satisfactory purity (≥95%), as verified by 1 H and 13 C NMR spectroscopy, high‐resolution mass spectroscopy, infrared, and chiral HPLC analysis …”

“…The dual‐protected amino acid derivatives were prepared following a methodology developed by our research group (Scheme ). Initially N ‐Boc protected amino acids were synthesized by the following method: to an amino acid solution ( l ‐alanine, l ‐valine, l ‐leucine, l ‐isoleucine, or l ‐phenylalanine ‐ 10.0 mmol) in water/1,4‐dioxane (3:2 v/v), 0.5 g of Na 2 CO 3 was added, followed by addition of Boc anhydride (15.0 mmol, 1.5 eq).…”

Cytotoxic Activity of Synthetic Chiral Amino Acid Derivatives

“…By employing the synthetic methodology developed by our research group, 23 32 derivatives from L-amino acids and 2 from D,L-alanine were prepared in moderate to good yields. Furthermore, the previously prepared N-alkyl diamine 39 was successfully employed as nucleophile in the attainment of the derivative 8.…”

Theoretical Study on the Epimerization of Azlactone Rings: Keto–Enol Tautomerism or Base-Mediated Racemization?

“…8 Furthermore, a very interesting aspect about oxazolones bearing a hydrogen linked to C4 is that, to the best of our knowledge, a racemization-free synthesis has never been achieved when the C2 substituent is an aryl or alkyl group, even when employing a single amino acid enantiomer as the initial substrate. 9 In the few reports involving enantiomerically pure oxazolones, 10,11 a modification of the C2 substituent of the cycle is necessary to make racemization less likely to occur, affording 2-alcoxy-azlactones by the cyclization of carbamate-protected amino acids. 12…”