Synthesis and Derivatization of 3‐Aroyl Pyroglutamic Acids. Issue 7 (17th February 2020)

• Record Type: Journal Article
• Authors: Markus, Jozef; Puchľová, Eva; Pinčeková, Lucia; Moncol, Ján; Doháňošová, Jana; Berkeš, Dušan; Caletková, Oľga
• Is Part Of: ChemistrySelect. Volume 5:Issue 7(2020)
• Page Start: 2115
• Page End: 2118
• Publication Date: 2020-02-17
• Subjects: amino acids -- asymmetric synthesis -- cyclization -- α-hydroxylation -- lactams; Chemistry -- Periodicals; 540.5
• DOI: 10.1002/slct.202000162
• Languages: English
• ISSNs: 2365-6549

Abstract

Abstract: A practical synthetic strategy for the preparation of enantiomerically pure 3‐substituted pyroglutamic acid derivatives is described. This procedure pivots on fast 5‐ exo ‐tet cyclization of the chloroacetylated amino acids, prepared by the crystallization induced diastereomeric transformations (CIDT). Furthermore, oxidation of obtained 3‐substituted pyroglutamic acids afforded highly valuable scaffolds with a quaternary stereogenic center with excellent diastereoselectivity. The absolute stereochemical configuration of both, 3‐aroyl pyroglutamic acid and its 3‐hydroxylated derivative, was confirmed by single‐crystal X‐ray analysis. The versatility of the methodology is exemplified using a variety of aromatic and heteroaromatic amino acids. The efficiency of this chromatography‐free approach predestines it for the gram‐scale synthesis. This was demonstrated with the synthesis of more than 10 mmol of the model substrate with excellent overall yield and diastereoselectivity. Abstract : A novel and practical synthetic strategy for the preparation of enantiomerically pure 3‐substituted pyroglutamic acid derivatives is based on a fast 5‐ exo ‐tet cyclization of the chloroacetylated amino acids. Further oxidation of prepared products afforded highly valuable scaffolds with the quaternary stereogenic center with excellent diastereoselectivity.