Tailor‐Made Amino Acids and Fluorinated Motifs as Prominent Traits in Modern Pharmaceuticals

Abstract

Structural analysis of modern pharmaceutical practices allows for the identification of two rapidly growing trends: the introduction of tailor‐made amino acids and the exploitation of fluorinated motifs. Curiously, the former represents one of the most ubiquitous classes of naturally occurring compounds, whereas the latter is the most xenobiotic and comprised virtually entirely of man‐made derivatives. Herein, 39 selected compounds, featuring both of these traits in the same molecule, are profiled. The total synthesis, source of the corresponding amino acids and fluorinated residues, and medicinal chemistry aspects and biological properties of the molecules are discussed.

Asymmetric synthesis of (S)‐α‐(octyl)glycine via alkylation of Ni(II) complex of chiral glycine Schiff base

“…[2][3][4][5] Notably, over 30% of small-molecule drugs contain residues of Tailor-Made Amino Acids™. [2][3][4][5][6][7] One should also mention the growing acceptance and importance of AAs-based classes of drugs, such as peptidomimetics and peptides. [8][9][10][11][12][13] Subsequently, the current need for synthetic approaches affording enantiomerically pure Tailor-Made Amino Acids™ is at an all-time high.…”

“…The presence of the chemically orthogonal amino and carboxyl groups, combined with the stereogenic carbon and side chains, provides a three‐dimensional structural scaffold with an extraordinary degree of chemical/biological functionality. These properties render amino acids (AAs) ideally suited for design of complex molecules used as the basic components in modern pharmaceutical industry 2–5 . Notably, over 30% of small‐molecule drugs contain residues of Tailor‐Made Amino Acids™ 2–7 .…”

“…These properties render amino acids (AAs) ideally suited for design of complex molecules used as the basic components in modern pharmaceutical industry 2–5 . Notably, over 30% of small‐molecule drugs contain residues of Tailor‐Made Amino Acids™ 2–7 . One should also mention the growing acceptance and importance of AAs‐based classes of drugs, such as peptidomimetics and peptides 8–13 .…”

Asymmetric Synthesis of Tailor-Made Amino Acids Using Chiral Ni(II) Complexes of Schiff Bases. An Update of the Recent Literature

“…), combined with elements of chirality and diverse side chains, provides an exceptional three-dimensional structural framework with a high degree of chemical/biological functionality. These properties make AAs ideally suited for syntheses of complex molecules, highly diverse elements for SAR campaigns, basic components of modern pharmaceuticals [2][3][4][5]. In fact, over 30% of small-molecule drugs contain residues of tailor-made AAs [2,[6][7][8], while peptidomimetics and peptide class drugs are fully based on AAs [9][10][11][12].…”

Asymmetric Synthesis of Perfluoroalkylated α‐Amino Acids through Generated Radicals Using a Chiral Ni(II) Complex

“…Among them, fluorinated amino acids (FAAs) constitute an important niche in biochemistry. To date, FAAs are extensively applied in drug design [8–10] and as bioisosteres to enhance the bioactivity of peptides [11] . For example, avagacestat ( A ), a γ‐secretase inhibitor used in the treatment of Alzheimer disease, contains the residue of ( S )‐2‐amino‐5,5,5‐trifluoropentanoic acid; [12] fluorinated leucine is presented in odanacatib ( B ) – the cathepsin K inhibitor; [13] a selective induced nitric oxide synthase inhibitor ( C ) is based on 4,4‐difluorinated l ‐lysine; [14] trifluoromethylglutamic acid ( D ) is an important building block for the synthesis of modified calcium‐dependent antibiotics (CDAs) ( Figure 1).…”