Hany Fathy Nour

• Over the past few decades, bacterial resistance against antibiotics has emerged as a real threat to human health. Both mutation and most importantly the rapid exchange in genetic information between bacteria have resulted in multidrug resistant strains. A statement of the world health organization (WHO) predicts that by year 2020, 30% of all bacterial infections will not be successfully treated because of resistance. Accordingly, there is an urgent demand to develop innovative approaches for discovering new antibiotics. In an attempt to provide such approach, a novel class of chiral non-racemic macrocycles has been synthesized in [2+2]-cyclocondensation reactions of chiral dioxolane dihydrazides obtained from commercially available tartaric acids with aromatic dialdehydes. The novel macrocycles were named tetra-carbohydrazide cyclophanes and can be readily available in both enantiomeric forms (R or S). Three macrocycles underwent successfully dynamic exchange to generate a small dynamic combinatorial library (DCL) of eight members. Electrospray ionization time-of-flight mass spectrometry (ESI-TOF/MS) and tandem MS showed potential recognition of a one member from the generated DCL to AcNH-L-Lys- D-Ala-D-Ala-Gly-COOH oligopeptide which mimics bacterial cell wall structure. Reactions of dioxolane dihydrazides with aromatic diiso- and isocyanates afforded novel classes of tetra-(hydrazinecarboxamide) cyclophanes and bis-N-substituted hydrazinecarboxamide receptors, which also showed potential recognition to a wide selection of chiral carboxylic acids and oligopeptides as confirmed by ESI-TOF/MS.