Premium
Pyroglutamic Acid in Drug Synthesis, Part 1 A Method for the Synthesis of Enantiomerically Pure 4‐Alkyl‐4‐arylpyroglutamic Acids
Author(s) -
Fleischhacker Wilhelm,
Riedl Thomas,
Völlenkle Horst,
Noe Christian R.
Publication year - 1996
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19963290108
Subject(s) - pyroglutamic acid , alkylation , acetal , chemistry , aldol reaction , yield (engineering) , alkyl , stereochemistry , methyl iodide , lactam , cleavage (geology) , total synthesis , derivative (finance) , iodide , organic chemistry , catalysis , amino acid , biochemistry , materials science , geotechnical engineering , fracture (geology) , economics , financial economics , engineering , metallurgy
Synthesis of the title compounds is described, starting from alkylation of the pyroglutaminol‐acetal 4a [1] at the α‐lactam position C‐6 with methyl iodide. Subsequent addition of 2‐cyclohexen‐1‐one led to diastereoselective formation of the 1,2‐aldol addition product 7b/7c , which after dehydratization was aromatized with DDQ to yield the 6‐methyl‐6‐phenyl derivative 7h. Acetal cleavage and Jones oxidation yielded 4,4‐disubstituted, enantiomerically pure pyroglutamic acid 3b. X‐ray analysis confirmed the assignment of the configuration of the newly created chiral centre.