Studies in the chemistry of glutarimides
This thesis describes investigations made into the chemistry of C-4 substituted glutarimides. It develops two contrasting approaches to this goal, which reflect the previous synthetic interests in the area. The glutarimides made were screened for potential agrochemical actions at Shell Research Centre, Sittingbourne. The anti-Leukemia alkaloid sesbanimide has prompted much recent work into the formation of glutarimides attached to functionalised precursors. This chemistry was developed by the formation of a glutarimide from C-5 of xylodialdofuranose, using standard methods. Wittig extension of the aldehyde, followed by Michael addition of malonate and dealkoxycarbonylation gave a glutarate diester, this was converted to the glutarimide via an anhydride. A glutarimide was similarly constructed from a β-ribose residue, forming an analogue of the β-C-nucleosides. An approach to the epimeric α- ribo-glutarimide was also made. The α- and β-riboaldehydes, from which the glutarimides were elaborated, were each formed stereospecifically by the ring contractions of a pyranose triflate. Synthetic interest towards the so-called glutarimide antibiotics has centred around the elaboration of a side chain attached to a pre-formed glutarimide. The common precursors in this work were glutarimides attached via C-4 to β-acetyl functions. The corresponding side chain in this work was activated, in a novel manner, by the formation of a stabilized ylid at that centre. Wittig reactions between this ylid and a number of carbonyl compounds were achieved. Some of these Wittig products were elaborated further, a number of simple heterocycles were thus formed, attached to glutarimide via a 1-carbon extension. Using a carbohydrate derived side chain an attempt to form a glutarimide attached to a shikimate-related residue was made, by means of an intramolecular aldol cyclisation. An N-substituted glutarimide was formed in a novel reaction between an iminophosphorane and glutaric anhydride. Many of these synthetic glutarimides exhibited some biological activity.