Ashley L. Dey

Mankind has immensely benefited from the first marketed antibacterial drug i.e. Salvarsan® in 1910 to the recently released Vaborem®, and the discovery of penicillin gave birth to the modern age of antibacterial treatment. Since the ‘golden age’ of antibacterial discovery (from the ‘40s to the ‘60s), in which most common antibacterial agents were discovered, antibacterial discovery has slowed dramatically with no new antibacterial scaffolds being introduced from 1962 until 2000. Recent developments in Oxford have led to identification of non-β-lactam indole carboxylates as potent metallo-β-lactamase inhibitors; as a result, and in extension of the aforementioned endeavours in combating antibacterial resistance, herein this work reports a set of novel nitrofuranyl indole carboxylates (NInCs) which are thought to have potential to be developed into antibacterial drug conjugates. Inasmuch as stable ester prodrugs of the aforementioned NInCs may be biologically inactive, this work also presents various methods for ester hydrolysis of these potential antibacterial drug conjugates together with some modification to their cleavable linkers.

Imidazo-fused diazaborines which serve as intermediary structures somewhat along benzene and borazine had been of particular interest to Dewar and Snyder more than 60 years ago. To this end, Dewar utilised his ‘π- complex theory’ so as to represent ‘borazaros’ as ‘quadrivalent’ species; however, sadly modern representations have deviated and leapt into ‘trivalent’ counterparts. Inasmuch as bonding in boron species has never been straightforward to such an extent that the orthodox ‘ethane’ like diborane i.e. H3B–BH3 which conferred to the paradigmatic rules of molecular structure, in particular, hybridisation and electronegativity was later evolved to a more realistic ‘3-centre 2-electron’ bonding, so as to give the lie to the purported diborane structures of X-ray diffractors, herein 11B NMR together with IR spectroscopy sheds light on the nature of bonding in borazaros and ‘caged’ cyclic oxazaborons so as to reenforce and reinvigorate the old literature which could be of interests to the synthetic and medicinal chemist alike.

Anisotropically induced ring currents are not confined to Hückel’s aromatics, and many non-aromatic compounds, in particular, cyclopropane exhibit ring currents in an applied magnetic field. To this end, aromatic protons of 5-nitrofurfural give rise to two signals in its 1H NMR spectrum in CDCl3 which as expected, are only ~ ±0.1 ppm apart; however, in marked contrast to 5-nitrofurfural, the analogous aforementioned protons of (E)- 5-nitrofuran-2-yl methylene hydrazine are nearly ±1.0 ppm apart in its 1H NMR spectrum in DMSO-d6. This anomaly may, though it need not of necessity, suggest that the hydrazone moiety in (E)-5-nitrofuran-2-yl methylene hydrazine force the furan ring into a puckered non-aromatic ring so as to pave the way for an induced ring current in an applied magnetic field. 5-nitro-N'-5-nitrofuran-2-carbonyl furan-2-carbohydrazide also appears to exhibit a similar perturbation; however, to a lesser extent.

Most 5-nitrofuranyl derivatives, in particular, the frequently used 5-nitrofurfural building block in synthesis, are coloured compounds and their intrinsic colours can be a good indication of their purity by virtue of their specific extended π-delocalisation. To this end, the work herein reports a first-of-its-kind anhydrous synthesis of (E)-5- nitrofuran-2-yl methylene hydrazine, 5-nitrofuran-2-carbohydrazide, and its dimeric 5-nitro-N'-5-nitrofuran-2- carbonyl furan-2-carbohydrazide, alongside their intrinsic colours, and most importantly their reactivity towards several deuterated solvents together with their 1H and 13C NMR features in an attempt to unravel the basis of discrepancies in the appearance of purported (E)-5-nitrofuran-2-yl methylene hydrazine of high purity in the literature and that obtained herein.