Pseudopolymorphism: occurrences of hydrogen bonding organic solvents in molecular crystals

Multi-point recognition with strong and weak hydrogen bonds between solvent and solute molecules facilitates the retention of organic solvents in crystals

Isostructurality in crystalline oxa-androgens: a case of C-O-···O and C-H···O interaction mimicry and solid solution formation

A C-H···O interaction in 2-oxa-4-androstene-3,17-dione is replaced by a C-O-H···O hydrogen bond in the isostructural 6a-hydroxy analogue, and these compounds form a binary solid solution, showing the similarity of these two crystal structures

Multiple molecules in the crystallographic asymmetric unit. Self host-guest and doubly interpenetrated hydrogen bond networks in a pair of keto-bisphenols

The presence of two molecules in the crystallographic asymmetric unit in a pair of closely related keto-bisphenols that differ by a methyl substituent only, leads to open frameworks that fill space through self-inclusion in one case, and through interpenetration in the other

Synthesis, x-ray crystal structures and biological evaluation of some mono- and bi-cyclic 1,3-diazetidin-2-ones: non-natural β -lactam analogues

Mono- and bi-cyclic 1,3-diazetidin-2-ones (aza-β -lactams) are synthesised and evaluated as non-natural analogues of β -lactams. The aza-β -lactams are designed on the principle that their reaction with active site serine hydroxy will form a carbamoyl-enzyme intermediate that is sluggish to hydrolysis. The synthesis of racemic mono- and bi-cyclic aza-β -lactams is carried out starting from pyrimidinone 18 which is transformed to the densely functionalised substrate 20. The chemical reactivity of tricarbonyl 20 for selective functional group manipulation was first assessed and then it was transformed to amino alcohol 24. Cyclisation of 24 affords aza-carbapenams and its homologation followed by aldol cyclisation provides access to aza-carbacephams. The X-ray structures of aza-carbapenam 35 and aza-carbacepham 42 suggest that the structural requirements for biological activity in β -lactams are fulfilled. An unexpected ozonolysis product, phenol 52 resolves spontaneously during crystallisation and its crystal structure was also determined. The biological activity of the novel mono- and bi-cyclic aza-β -lactams was evaluated with potent gram-positive bacterial strain, Bacillus subtilis and compared with β -lactam antibiotics, ampicillin and penicillin G. Of the 19 aza-β -lactams tested, eight compounds show inhibition better than the standards while another eight are of comparable activity. This study shows that aza-β -lactams represent a novel and non-natural lead towards serine peptidase inhibitors