Allan Patrick Marchington

4-Amino-2-(aryl)-butylbenzamides and Their conformationally constrained analogues. Potent antagonists of the human neurokinin-2 (NK2) receptor

A library, evaluating a range of piperazines, piperidines and acyclic amines, as replacements for the 4-hydroxy-4-phenylpiperidine moiety in lead (1b) was prepared. These efforts identified the 4-((N)-benzimidazolone)piperidine analogue (2a) which was further optimised using classical single-compound synthesis to yield the 3-((N)-morpholino)azetidine (2j). Conformationally constrained analogues of (2j), generally offered no potency advantage in this particular series.

Stereocontrolled synthesis of novel enantiomerically pure sulfides and selenides from (+)-camphor and (+)-camphor-10-sulfonyl chloride

Abstract Synthetic approaches to novel enantiomerically pure sulfides and selenides derived from (+)-camphor and (+)-camphor-10-sulfonate esters are described. Lewis acid mediated hemiacetal formation between a camphor-derived ketone and a thiol or selenol, and subsequent in situ reduction using triethylsilane selectively gives the exo-sulfide or -selenide in moderate overall yields. The initial sulfonate ester products can be converted into the corresponding sulfones by subsequent treatment with Grignard or organolithium reagents.

Synthesis of new potential aminopeptidase inhibitors by Lewis acid induced rearrangement of 2,3-epoxy amines and regiospecific nucleophilic trapping of aziridinium ion intermediates with α-amino esters

Abstract Optically active 2,3-epoxy alcohols, prepared using the Sharpless asymmetric epoxidation, are readily converted into 2,3-epoxy amines which, upon treatment with TMSOTf, undergo stereospecific rearrangement to the corresponding 3-trimethylsilyloxy-1,2-aziridinium triflates. These electrophilic species undergo efficient regiospecific nucleophilic ring opening at C-1 using α-amino esters with full control of absolute and relative stereochemistry. The products are structurally related to the known potent aminopeptidase inhibitor bestatin and other biologically active molecules.

Selective alkylation of β-ketoester enolates using O-methyl aminosulfoxonium salts; the first example of C-alkylation using sulfoxonium salt electrophiles

The alkylation of β-ketoester enolates with O-methyl aminosulfoxonium tetraphenylborate salts is reported; good to excellent selectivity for C-vs. O-alkylation is observed, and is found to be dependent on the nature of the β-ketoester, solvent, metal counterion and aminosulfoxonium salt.

Generation of homochiral aziridinium ion intermediates derived from2,3-epoxy amines: regiospecific nucleophilic trapping with nitrogennucleophiles. Application in the synthesis of novelmorpholinosphingolipid analogues with potential glucosylceramidesynthase inhibitory activity

The Lewis acid induced rearrangement of 2,3-epoxy amines into the corresponding 2-trimethylsilyloxymethylaziridinium ions is described. Such intermediates have been characterised by 1H NMR spectroscopy, and react with nitrogen nucleophiles regiospecifically to form 1-substituted 2,3-amino alcohols in good to excellent yields and with full stereochemical control. This methodology has been applied to the synthesis of a potential inhibitor of glucosylceramide synthase, a promising target for cancer chemotherapy.

The first X-ray crystal structure of an O-alkyl aminosulfoxonium salt: conclusive evidence for O-alkylation of sulfinamides and planarity of nitrogen

The X-ray crystal structure of O-methyl (2R,5R)-bis(methoxymethyl)pyrrolidin-1-yl-(S)-p-tolylaminosulfoxonium tetraphenylborate 5 is reported: this is the first X-ray crystal structure of an O-alkyl aminosulfoxonium salt, and provides conclusive evidence that alkylation of sulfinamides occurs on oxygen.