Synthesis of Lactam-Based Peptidomimetics from β-Keto Esters and β-Keto Amides

Abstract

Pyrrolidinone-based peptidomimetics, in which the peptide bond is forced to adopt either a cis or trans geometry, have been prepared from readily available amino acids. Peptidomimetics based on amino acid side chain to side chain cyclization (17), side chain to N cyclization (18), and R-H to side chain cyclization (28) have been developed. A key step in the syntheses is the treatment of a peptide-based β-keto ester or amide with an amine. The absolute configuration of compounds 28 was established using Seebach oxazolidinone chemistry.

Preparation of [1,2,3,4,5‐13C5]‐5‐Amino‐4‐oxopentanoic Acid (ALA) − Design of a Synthetic Scheme to Prepare Any 13C‐ and 15N‐Isotopomer with High Isotopic Enrichment

“…The analytical data for compound 14 are in complete agreement with those published in the literature. [18,19] In principle, this could be a useful result because compound 14 has the full carbon skeleton of ALA which could possibly be converted into ALA by simple reaction steps. Nitrosation of compound 14 could lead to the introduction of a nitrogen function in the vinylic position, which on catalytic reduction and subsequent hydrolysis might lead to ALA.…”

Efficient Total Synthesis of Pulchellalactam, a CD45 Protein Tyrosine Phosphatase Inhibitor

“…Recent synthetic studies toward lactam-containing heterocycles for use in biological discovery efforts have been intense, − but no general synthetic method that is applicable to the liquid- or solid-phase synthesis of 3-pyrrolin-2-ones substituted at the 4-position has yet been reported. In this total synthesis, the key steps of our approach were focused on the formation of the 3-pyrrolin-2-one ring and its condensation with an aldehyde.…”

Propargylation of Ugi Amide Dianion: An Entry into Pyrrolidinone and Benzoindolizidine Alkaloid Analogues

“…Next, we decided to evaluate the synthetic interest of these new cyclic enamides. , Their enamine nature should be associated with potential iminium formation under acidic conditions. This nature can be confirmed by the facile addition of indole to 3a under treatment with a catalytic amount of tosic acid (10 mol %) in toluene at 60 °C (Scheme ).…”