Structures of Azole‐Containing Macrocyclic Peptides

Abstract

The substantial subclass of known organic heterocyclic compounds containing a fivemembered aromatic ring with at least one nitrogen atom is termed as the azoles [1]. This parent class of heterocycles, together with its reduced analogs azolines and azolidines, can be found in various important biomolecules, such as amino acid building blocks (proline, histidine, tryptophan) of many proteins (myoglobin, carboxypeptidase A, azurin, etc.), natural tetrapyrrolic pigments (hemoglobin, chlorophyll), vitamins (thiamine, cobalamin, biotin), and nucleobases (adenine, guanine) [2]. In addition, many secondary metabolites of living organisms, many alkaloids contain five-membered aza-heterocycles and demonstrate a wide range of physiological properties [3]. The importance of azole-related synthetic organic compounds is also obvious in everyday life, covering various fields of application in human civilization and economy. For example, synthetic pyrrole and imidazole derivatives are among the most commonly prescribed and top-selling active pharmaceutical ingredients (APIs) (Scheme 23.1) [4], while some of the most profitable crop-protection chemicals also incorporate five-membered aza-, oxaza-, and thiazaheterocycles (Scheme 23.2) [5]. Several industrial food additives contain pyrazole (E102, E107) and imidazole (E234, E239, E626-629, E630-633), as well as thiazole (E239, E700) and isothiazole (E954) substructures [6].Apart from the life sciences and related chemical technologies, other branches of the chemical industry produce and utilize azole derivatives of high structural diversity. For example, quaternary imidazolium and pyrrolium salts with ionic liquid properties excel as reaction mediums, extraction and processing solvents, heat storage and transfer fluids, low-temperature electrolytes, lubricants, or seals [7]. Modeling of Molecular Properties, First Edition. Edited by Peter Comba. Scheme 23.2 Chemical structure of some well-known azole-containing pesticides. 366j 23 Structures of Azole-Containing Macrocyclic Peptides 7 Patellamide D Scheme 23.3 Structural formulae of selected cyclohexa-, cyclohepta-, and cyclooctapeptide Lissoclinum alkaloids. 23.2 Azole-Containing Macrocyclic Peptides in Nature j367 Figure 23.2 Optimized structures of lissoclinamide 7 (3, left) and cis,cis-ceratospongamide (4), using B3LYP/6-31G Ã . 372j 23 Structures of Azole-Containing Macrocyclic Peptides

Bio-inspired Herringbone Foldamers: Strategy for Changing the Structure of Helices

“…In previous studies, we were able to show that an alkyl group (e.g., a methyl or isopropyl group) leads to a significant deviation of the dihedral angle θ­(C1–N2–C3–C4) from 180°. , Model studies have shown that an imidazole with a methyl group attached to the δ position have two minima: one thereof shows a dihedral angle θ­(C1–N2–C3–C4) of −156°; the strongly bent one has a dihedral angle of −102°. The first conformation is stabilized by interaction between the σ­(C3–Me) orbital and the π imidazole * orbital; the second one exhibits a stabilizing interaction between the σ*­(C3–N2) orbital and the π imidazole orbital …”