Berkeleylactone A is a potent 16-membered macrolactone antibiotic, recently isolated from a coculture of Berkeley Pit Lake fungi. Although its antimicrobial activity has already been investigated, little is known about...

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.

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.

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.