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Synthesis and Derivatization of 3‐Aroyl Pyroglutamic Acids
Author(s) -
Markus Jozef,
Puchľová Eva,
Pinčeková Lucia,
Moncol Ján,
Doháňošová Jana,
Berkeš Dušan,
Caletková Oľga
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202000162
Subject(s) - pyroglutamic acid , stereocenter , diastereomer , chemistry , derivatization , yield (engineering) , stereochemistry , absolute configuration , derivative (finance) , amino acid , crystallization , organic chemistry , combinatorial chemistry , enantioselective synthesis , high performance liquid chromatography , catalysis , biochemistry , materials science , economics , financial economics , metallurgy
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.