Diketomorpholines: Synthetic Accessibility and Utilization

Abstract

Diketomorpholines (DKMs; morpholine-2,5-diones) possess a six-membered ring with a lactone and lactam moiety and belong to the family of cyclodepsipeptides. In this review, the synthetic accessibility of DKMs is summarized and their utilization, in particular, for ring-opening polymerization reactions, is highlighted. The occurrence of the DKM scaffold in natural products encompasses small monocyclic compounds but also complex, polycyclic representatives with a fused DKM ring.

30th Annual GP2A Medicinal Chemistry Conference

“…Imino acid derived diketomorpholines were conceptualized as generally applicable key intermediates prepared through solid-phase synthesis. Due to their susceptibility to ring cleavage upon treatment with primary amines [ 132 ], these diketomorpholines were appropriate educts for a traceless generation of bioactive compounds ( Figure 27 ). This approach led to a compound library whose members were prepared under bioassay-compatible conditions and can directly subjected to the in situ evaluation, allowing a fast prediction of hit compounds.…”

An Optimized and Universal Protocol for the Synthesis of Morpholine-2,5-Diones from Natural Hydrophobic Amino Acids and Their Mixture

“…MDs can be found naturally in small quantities in flowers, mushrooms, , sea cucumbers, bacteria, and algae and in earth samples . The production of MDs using AAs as the raw material has been performed via many different methods using various synthesis paths, conditions, and catalysts. ,− The most common and easiest route for MD production consists of a two-step process wherein the AA is first reacted with an α-halogenated acyl halide to form a N -(α-haloacyl)-α-amino acid (ANX) (Figure B) . This reaction is usually performed in solution with a base as to favor the reaction of the halogenated reagent with the amine group over the acid group.…”