Raymond C. F. Jones

Amide bond isosteres: Imidazolines in pseudopeptide chemistry

Abstract The 2-imidazoline ring has been incorporated as an amide bondreplacement into pseudodipeptides, a pseudotripeptide, andpseudopentapeptide enkephalin analogues.

Annulation of imidazolines: synthesis of imidazo[1,2-a]pyridones

Abstract The enaminoester 1-benzyl-2-(ethoxycarbonylmethylene)-imidazolidine undergoes N-acylation and conjugate C-addition with α,β-unsaturated acyl imidazolides to afford imidazo[1,2- a ]pyridones.

A new route to homochiral piperidines

Abstract The synthesis of an enantiomeric pair of enaminoesters from phenylglycine is described. Conjugate addition to α,β-enones, reductive cyclization-fragmentation to octahydroimidazopyridines and further reduction to remove the auxiliary atoms, completes a new route to homochiral piperidines in which the enaminoesters function as homochiral ‘ethanal enamines’.

Conjugate addition of imidazolines: a protocol for 1,4-addition to enones and other acceptors

Abstract The enaminoester 1-benzyl-2-ethoxycarbonylmethyleneimidazolidine reacts with α,β-enones and other Michael acceptors to give 1,4-adducts; removal of the ethoxycarbonyl group completes overall conjugate addition of the imidazoline α-anion (which itself adds 1,2 to enones), and hydrolysis affords carboxylic acids.

Structural elucidation studies of erythromycins by electrospray tandem mass spectrometry.

Erythromycin A (EryA), sec-butyl erythromycin B (SEryB), oleandomycin (Olean) and a synthetic derivative, roxithromycin (Rox), were used to investigate the fragmentation of polyketide macrolide antibiotics by collision induced dissociation (CID) tandem mass spectrometry (MS/MS). Analyses were performed with two commercially available mass spectrometers: a Q-TOF hybrid quadrupole time-of-flight instrument and a BioApex II (4.7 Tesla) Fourier transform ion cyclotron resonance (FTICR) instrument both equipped with electrospray ionisation (ESI) sources. One of the first fragmentation processes is the loss of an H(2)O molecule from the [M+H](+) ion. EryA has three hydroxyl groups on the polyketide ring and loses three H(2)O molecules during CID. This study indicates that these facts are not necessarily related. Deuterium exchange experiments were carried out in order to isotopically label free hydroxyl groups. (18)O-exchange experiments were also carried out in order to label the carbonyl group at the 9-position. In EryA and its analogue the first H(2)O loss shifts in mass from loss of 18 Da to loss of 20 Da in deuterated solvents. For both molecules the loss also shifts in mass from loss of 18 Da to loss of 20 Da during the (18)O-exchange experiments. This suggests that the first loss of H(2)O is from the 9-position carbonyl group, indicating that this, and not the nitrogen of the amino sugar, is the site of protonation of the activated MH(+) ions. For Rox the initial loss of H(2)O is replaced by loss of the 9-position oxime group, the rest of the fragmentation sequence being the same as for EryA. For Olean, there is no H(2)O loss from the parent ion. The results have allowed the proposal of a mechanism for the first loss of H(2)O in the EryA MS/MS fragmentation.

Annulation of imidazolines with bis-electrophiles: Synthesis of imidazo[1,2-a]pyridines

Abstract 1-Benzyl-2-(ethoxycarbonylmethylene)-2,3,4,5-tetrahydroimidazole undergoes annulation with a variety of 1,3-bis-electrophiles (α,β-unsaturated acid derivatives, β-ketoesters, α,β-unsaturated aldehydes) to form imidazo[1,2-a]pyridines.

Cycloaddition of homochiral imidazolinium ylides: A route to optically active pyrroloimidazoles

Abstract The synthesis of either enantiomer of 1-benzyl-4-phenyl-2-imidazoline from phenylglycine is described. ‘One-pot’ generation and enantioselective 1,3-dipolar cycloaddition of homochiral azomethine ylides prepared from these imidazolines with a range of alkene dipolarophiles affords optically active hexahydropyrroloimidazole adducts.

Solid-phase synthesis of substituted 2-aminomethylbenzimidazoles

Abstract Resin-bound 4-fluoro-3-nitrobenzoic acid is converted by reaction with a range of amines and reduction, to substituted 1,2-diaminobenzenes, whose reaction with activated amino acids followed by acid-catalyzed cyclisation gave resin-bound benzimidazoles; Fmoc-deprotection, acylation and TFA-mediated cleavage gave substituted 2-aminomethylbenzimidazoles via a new solid support strategy.

1,3,4-Oxadiazole formation; a novel solid support strategy

Abstract A new approach to the synthesis of 1,3,4-oxadiazoles on solid support is described. Resin bound 1-acyl thiosemicarbazides were treated with a variety of dehydrating agents at different temperatures, which revealed that thiosemicarbazides were effectively cyclised by 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDC·HCl); mild acidic cleavage from the solid support released the substituted 1,3,4-oxadiazoles in excellent purity.

Annulation of imidazolines: A 1,3-dipolar cycloaddition route to pyrroloimidazoles, pyrrolidines and pyrroles

Abstract Azomethine ylides, prepared from imidazolinium salts, undergo 1,3-dipolar cycloaddition with a variety of dipolarophiles to produce hexahydropyrrolo[1,2- a ]imidazoles, which are reduced to pyrrolidines; with 2-chloroacrylonitrile as dipolarophile, pyrroles can be prepared from the cycloadducts by elimination.