Synthesis of Constrained Peptidomimetics Containing 2‐Oxo‐1,3‐oxazolidine‐4‐carboxylic Acids

Abstract

Sulfonyl peptides containing a serine or threonine residue undergo cyclization with bis(succinimidyl) carbonate (DSC) and diisopropylethylamine (DIPEA) to give peptides with a 2‐oxo‐1,3‐oxazolidine‐4‐carboxylate (Oxd) group, either in solution or in the solid phase. The position of the serine or threonine residue in the sequence is relatively unimportant. Under the same conditions, the corresponding Fmoc‐ or Boc‐peptides gave dehydration products, in agreement to previous studies. The protocol constitutes a valuable approach to the preparation of oxazolidinone‐containing peptides, which are a recently emerging class of constrained peptidomimetics. As a representative example, an Oxd analogue of the endogenous opioid peptide endomorphin‐1, characterized by an all‐trans conformation, was readily prepared.

Integrin Ligands with α/β‐Hybrid Peptide Structure: Design, Bioactivity, and Conformational Aspects

“…This Amo ring incorporated the α‐hydroxy‐β‐amino acid and the amine function of the adjacent residue. This result was complementary to the previously observed reactions with sequences including β‐hydroxy‐α‐amino acids, which gave under the same conditions oxazolidinone (Oxd)‐peptides . Indeed, depending on the stereochemistry, linear peptides including two consecutive β‐hydroxy‐α‐amino acids gave rise to sequences Oxd‐Oxd or ΔAbu‐Oxd (ΔAbu, dehydroaminobutanoic acid).…”

Expedient synthesis of pseudo-Pro-containing peptides: towards constrained peptidomimetics and foldamers

“…The treatment of Ms-Ala-Ser-PheNH 2 (1d) with DSC in the presence of a catalytic amount of DIPEA did not give rise to the formation of the Oxd-peptide (entry 18); the use of 1.2 equiv. of DIPEA (entry 19) or DMAP (entry 20) afforded the product only in traces.…”

“…18 In this work we considerably expand the scope of our preliminarily described preparation of peptides containing the Oxd ring. 19 The reaction proceeds by the direct cyclization of N-sulfonyl peptides containing a Ser residue (Scheme 1) by treatment with bis(succinimidyl) carbonate (DSC) and diisopropylethylamine (DIPEA).…”

Routes to N-glycinamide oxazolidinone derivatives: The reaction of 4-trityloxymethyl-3-oxa-1-azabicyclo[3.1.0]hexan-2-one with active halides

“…[1][2][3] Oxazolidinones and related linkers have been used previously to prepare a variety of peptidomimetics. The use of both the oxazolidin-4-one type rings (1) 4 as well as oxazolidine-2-one rings (2) [5][6][7][8][9] (Figure 1) have been reported. In both cases, the oxazolidinone ring has generally been used to induce formation of secondary structures.…”