Tailor‐Made Amino Acids in Pharmaceutical Industry: Synthetic Approaches to Aza‐Tryptophan Derivatives

Abstract

Over the recent years there has been a noticeable upsurge of interest in aza‐analogs of tryptophan which are isosteric to the latter and found numerous applications in medicinal, bioorganic chemistry, and peptide research. In the present review article, five aza‐tryptophan derivatives are profiled, including aza‐substitution in the positions 2, on the five‐membered ring, as well as in positions 4, 5, 6, and 7 on the six‐membered ring. A detailed and comprehensive literature overview of the synthetic methods for the preparation of these aza‐tryptophans is presented and general facets of the biological properties and most promising applications are discussed.

Asymmetric Metal‐Templated Route to Amino Acids with 3‐Spiropyrrolidine Oxindole Core via a 1,3‐Dipolar Addition of Azomethine Ylides to a Chiral Dehydroalanine Ni(II) Complex

“…Nowadays, chiral unnatural amino acids (AAs) are in a great demand in biochemistry and pharmaceutical industry due to their extensive application for the modification of peptides and proteins in order to improve their metabolic stability, aggregation and pharmacokinetic properties, [1] and using for the design of new blockbuster drugs [2] . Among them, AAs featuring heterocyclic cores have a considerable and essential interest [2c,e] . In particular, a 3‐spiropyrrolidine oxindole skeletal is presented in various biologically active compounds with pronounced therapeutic properties; [3,4] for example, such as Spirotryprostatine A, [4a] the substance I with antitumor activity [4c] and the compound II , containing AA fragment, has an anticancer activity [4e] (Scheme 1A).…”

Asymmetric Metal‐Templated Approach to Amino Acids with a CF3‐Containing 3,2’‐Pyrrolidinyl Spirooxindole Core via a Michael/Mannich [3+2]‐Cycloaddition Reaction

“…In particular, the introduction of a fluorine atom into the molecules increases their metabolic stability, bioavailability and favourable pharmacokinetic properties [3] . On the other hand, the incorporation of heterocycles into the AA residue can lead to the pronounced therapeutic properties [2d,4] . One of the privileged classes of heterocycles are the spirocyclic oxindoles, often found in natural products with potential pharmacokinetic activity [5] .…”

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

“…Asymmetric synthesis of functionalized amino acids is a subject of intense research because these compounds are of great demand for pharmaceutical industry, health care, and food production [ 1 – 3 ]. Various approaches to enantiomerically enriched amino acids have been developed employing chiral auxiliaries [ 4 – 5 ] and asymmetric phase-transfer catalysis [ 6 – 7 ].…”