Synthesis of constrained analogues of tryptophan

Abstract

SummaryA Lewis acid-catalysed diastereoselective [4 + 2] cycloaddition of vinylindoles and methyl 2-acetamidoacrylate, leading to methyl 3-acetamido-1,2,3,4-tetrahydrocarbazole-3-carboxylate derivatives, is described. Treatment of the obtained cycloadducts under hydrolytic conditions results in the preparation of a small library of compounds bearing the free amino acid function at C-3 and pertaining to the class of constrained tryptophan analogues.

A novel synthesis of chromone based unnatural $$\upalpha $$ α -amino acid derivatives

“…13 In recent years, both pharmaceutical companies and academics became interested in the design and synthesis of peptidomimetics and peptide analogues as new therapeutic drugs. [14][15][16] The progress of Medicinal Chemistry in these fields was probably inspired by the biochemical advancements in the recognition of new naturally occurring peptides possessing useful biological activities and in the elucidation of their physiological functions. 17 However, peptides assembled with natural amino acids present several drawbacks related to metabolic instability, deficiency in selective interactions and reduced oral absorption that prevent their use in therapy.…”

“…The compound 16 was prepared following the similar procedure as 12 starting from procedure 2-hydroxy-5-methy-acetophenone 6b in a five step synthetic sequence. Various N-protected chromo based amino acid derivatives (13)(14)(15)(16)(17)(18)(19) were prepared using the standard protecting group procedure. 38 The N-acetyl protected amino acid 15 was subjected to chiral HPLC separation using Chiralcel OX-H column and hexane/EtOH (70:30) as the mobile phase ( Figure 2).…”

“…It is noteworthy to mention here that previously inaccessible 2-chromone amino acid conjugates (25)(26)(27)(28)(29)(30)(31) were synthesized in good yields as indicated in Table 1. The 3-chromone amino acid conjugates (13)(14)(15)(16)(17)(18)(19) were prepared in five easy synthetic steps in good yield. All these compounds were well characterized by 1 H-NMR, 13 C-NMR, LC-MS and HRMS analysis.…”

Design, synthesis, and biological evaluation of 2‐substituted‐2,3,4,9‐tetrahydrospiro‐β‐carboline‐3‐carboxylic acid derivatives as first‐in‐class mast cell stabilizers

“…Furthermore, there are key heterocyclic scaffolds and pharmacophores like 4 H ‐chromen‐4‐one (cromolyn), pyrido[1,2‐ a ]‐pyrimidin‐4‐one (pemirolast), phthalazin‐1‐one (azelastine), pyrano[3,2‐ g ]quinolone (nedocromil), and cyclohepta[3,4‐ b ]thiophen‐4‐one (ketotifen) which are well tolerated for mast cell stabilization activity. Recently the role of tryptophan in the suppression of mast cell activation has been confirmed by Silwal et al Tetrahydro‐β‐carboline is a constrained analog of tryptophan . Furthermore, dichotomine C, ML120B, and PS‐1142 are derivatives of β‐carboline which possess potent anti‐allergic effects.…”

Enantioseparation of tryptophan and its unnatural derivatives by nano‐LC on CSP‐teicoplanin silica based

“…In addition, due to their luminescence properties, they are also employed as probes for studying protein conformational dynamics in fluorescence resonance energy transfer . Other uses include the design and synthesis of peptidomimetics and peptide analogues as new therapeutic drugs overcoming the pharmacological limitations of bioactive peptides such as metabolic instability .…”