Synthesis, Structural Aspects, Antimicrobial Activity, and Ion Transport Investigations of Four New [1 + 1] Condensed 12‐Membered Cyclophane Amides

• Published in: Journal of heterocyclic chemistry Vol. 54; no. 2; pp. 952 - 958
• Main Authors: Gürbüz, Mustafa Ulvi, Aghatabay, Naz Mohammed, Karabulut, H. Rıza Ferhat
• Format: Journal Article
• Language: English
• Published: HOBOKEN Wiley 01.03.2017; Wiley Subscription Services, Inc
• Subjects: Antimicrobial agents; Chemistry; Chemistry, Organic; Ions; Physical Sciences; Science & Technology; PHANE NOMENCLATURE; DESIGN; DEPSIPEPTIDES; CYCLIC-PEPTIDES
• ISSN: 0022-152X; 1943-5193
• DOI: 10.1002/jhet.2659

Two new diamines (a, b) and their four [1 + 1] condensed macrocyclic peptides (c–f) were synthesized via dilution method affording the expected dilactams in reasonably high‐yield yields. The compounds were characterized by elemental analyses, mass, FT‐IR, 1H, and 13C NMR spectral data. Mass spectra reveal their [1 + 1] cyclic condensation. The macrocycles having two peptide units in the ring would constitute three configurational isomers: cisoid–cisoid, transoid–transoid, and cisoid–transoid. Their 1H and 13C NMR show one signal for each chemically equivalent SCH2 and CONH and could be assigned symmetrical structures lacking any configurational isomerism. The ion transport activity of the compounds (c) and (d) on Na+ and K+ ions were evaluated by CH2Cl2 liquid–liquid membrane method using a U tube system. Slightly higher affinity for potassium than sodium was also observed, which is undoubtedly related to the matching size of the cavity between K+ and cyclic peptides. The antimicrobial and antifungal activities of four macrocyclic amides (c, d, e, and f) were illuminated using disk diffusion method in dimethyl sulfoxide as well as the minimal inhibitory concentration dilution method, against several bacteria and yeast cultures. Comparing all methods, in most cases, the (e) and (f) compound seems to show slightly higher biological activity than the (c) and (d) macrocycles. This may be because of the presence of extra chlorine atoms on the exterior part of the molecules.