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Reagent‐induced asymmetric induction in addition reaction of reduced glutathione onto bis ‐Mannich chalcones
Author(s) -
Bernardes Aline,
D'Oliveira Giulio D. C.,
Silezin Aneta,
Kuzma Mónika,
Molnár Szilárd,
Noda Pérez Caridad,
Perjési Pál
Publication year - 2018
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.201700386
Subject(s) - chemistry , mannich reaction , reagent , glutathione , stereoselectivity , deprotonation , nucleophile , michael reaction , derivative (finance) , protonation , selectivity , asymmetric induction , medicinal chemistry , nucleophilic addition , amine gas treating , organic chemistry , enantioselective synthesis , catalysis , enzyme , ion , financial economics , economics
The stereochemistry of non‐enzyme catalyzed nucleophilic addition of GSH to 4′‐hydroxychalcone 1 and its bis ‐Mannich derivative 2 was investigated at different pH values (pH 3.2, 6.1, 7.4, and 8.0). The stereochemical outcome of the reactions was evaluated by HPLC‐UV‐Vis method. Under strongly acidic conditions (pH 3.2), an unexpected diastereoselective addition of GSH onto the bis ‐Mannich derivative 2 was observed. Such a selectivity could not be observed in the similar reaction of 2 with N ‐acetylcysteine. The observed stereoselectivity can be rationalized by ion‐pair formation between the protonated Mannich nitrogens and the deprotonated GSH(glutamate)‐carboxylate. To the best of our knowledge, this is the first example of reagent‐induced asymmetric induction in Michael‐type additions of thiols.