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Keywords = crystallization-induced diastereomer transformation

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15 pages, 1832 KiB  
Article
Total Synthesis of Hemerocallisamine I Paved by Gram-Scale Synthesis of (2S,4S)-4-Hydroxyglutamic Acid Lactone
by Lucia Pinčeková, Eva Jančiová, Dušan Berkeš, Róbert Gyepes, Andrej Kolarovič and Oľga Caletková
Molecules 2023, 28(5), 2177; https://doi.org/10.3390/molecules28052177 - 26 Feb 2023
Cited by 2 | Viewed by 2323
Abstract
Total synthesis of the 2-formylpyrrole alkaloid hemerocallisamine I is presented, both in racemic and enantiopure form. Our synthetic strategy involves (2S,4S)-4-hydroxyglutamic acid lactone as the key intermediate. Starting from an achiral substrate, the target stereogenic centers were introduced by [...] Read more.
Total synthesis of the 2-formylpyrrole alkaloid hemerocallisamine I is presented, both in racemic and enantiopure form. Our synthetic strategy involves (2S,4S)-4-hydroxyglutamic acid lactone as the key intermediate. Starting from an achiral substrate, the target stereogenic centers were introduced by means of crystallization-induced diastereomer transformation (CIDT) in a highly stereoselective fashion. A Maillard-type condensation was crucial to constructing the desired pyrrolic scaffold. Full article
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11 pages, 758 KiB  
Proceeding Paper
Synthesis of (2S,3S)-3-Aroyl Pyroglutamic Acid Amides
by Lucia Pincekova and Dusan Berkes
Chem. Proc. 2021, 3(1), 86; https://doi.org/10.3390/ecsoc-24-08377 - 14 Nov 2020
Cited by 1 | Viewed by 2105
Abstract
A new methodology for the asymmetric synthesis of enantiomerically enriched 3-aroyl pyroglutamic acid derivatives has been developed through effective 5-exo-tet cyclization of N-chloroacetyl aroylalanines. The three-step sequence starts with the synthesis of N-substituted (S,S)-2-amino-4-aryl-4-oxobutanoic acids [...] Read more.
A new methodology for the asymmetric synthesis of enantiomerically enriched 3-aroyl pyroglutamic acid derivatives has been developed through effective 5-exo-tet cyclization of N-chloroacetyl aroylalanines. The three-step sequence starts with the synthesis of N-substituted (S,S)-2-amino-4-aryl-4-oxobutanoic acids via highly diastereoselective tandem aza-Michael addition and crystallization-induced diastereomer transformation (CIDT). Their N-chloroacetylation followed by base-catalyzed cyclization and ultimate acid-catalyzed removal of chiral auxiliary without loss of stereochemical integrity furnishes the target substituted pyroglutamic acids. Finally, several series of their benzyl amides were prepared as 3-aroyl analogs of known P2X7 antagonists. Full article
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Scheme 1

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