Ray McCague

Application of enzymic Baeyer–Villiger oxidations of 2-substituted cycloalkanones to the total synthesis of (R)-(+)-lipoic acid

Oxidation of ketones 1a–h using a monooxygenase from Pseudomonas putida NCIMB 10007 gave the lactones 2a–h in optically active form: lactone 2h was converted into (R)-(+)-lipoic acid 9.

Whole cell catalysed kinetic resolution of 6-azabicyclo[3.2.0]hept-3-en-7-one: synthesis of (–)-cispentacin (FR 109615)

Enantioselective hydrolysis of the β-lactam (±)-2 using Rhodococcus equi provided (1R,5S)-6azabicyclo[3.2.0] hept-3-en-7-one (+)-2, a precursor of the antifungal agent cispentacin.

Enzyme-catalysed kinetic resolution of 4-endo-hydroxy-2-oxabicyclo[3.3.0]oct-7-en-3-one and employment of the pure enantiomers for the synthesis of anti-viral and hypocholestemic agents

The endo-hydroxylactone (+/-)-(1) was resolved by enantioselective acetylation using Candida cylindracea lipase or preferentially Pseudomonas fluorescens lipase (pfl). Alternatively the corresponding butyrate (+/-)-(3) was hydrolysed with pfl to give the ester (+)-(1S,4R,5S)-(3) and the alcohol (-)-(1R,4S,5R)-(1). The latter compound was converted into carbovir (-)-(1R,4S)-(12) while the ester (+)-(3) was transformed into the delta-lactone (+)-(3R,5S)-(18). The exo-hydroxylactone (+/-)-(2) was resolved less efficiently by a trans-esterification process employing pfl and vinyl acetate.

Enantioselective synthesis of the hydroxy-lactone moiety of mevinic acids

Abstract 2-Oxa-4 endo -hydroxybicyclo[3.3.0]-oct-7-en-3-one was resolved with Pseudomonas fluorescens lipase and one of the enantiomers was converted into a key intermediate in the synthesis of mevinic acids.

Conversion of (–)-4-hydroxy-2-oxabicyclo[3.3.0]oct-7-en-3-one into the anti-HIV agent carbovir

The lactone (±)-1 was resolved using Pseudomonas fluorescens lipase and vinyl acetate; the ester (–)-3 obtained by this process was subsequently converted into the anti-HIV agent carbovir (–)-9.

A novel sulfinylation of alkenes by tosyl cyanide with titanium(IV) chloride

Abstract Tosyl cyanide is activated by titanium(IV) chloride to generate a tolylsulfinyl chloride equivalent, which readily stereo- and regio-specifically adds to certain alkenes to provide β-chlorosulfoxides. These chlorides rapidly hydrolyse on silica gel to provide β-hydroxysulfoxides in stereocontrolled manner.

An asymmetric synthesis of α-amino acid derivatives from racemic ethyl N-phenylsulphonyl-α-bromoglycinate using homochiral aluminium complexes

Abstract Reactions of a racemic α-bromoglycinate 2 with readily available alkyl aluminium reagents modified by binaphthol derivatives produce α-amino acid analogues 3 in high yields and with asymmetric induction of up to 62 %.

CHEMOENZYMATIC SYNTHESIS OF A NOVEL LIGAND FOR RHODIUM-CATALYSED ASYMMETRIC HYDROGENATION

The hydrogenation of alkenes 7a–g using a chiral rhodium catalyst 6 (based on a bicyclo[3.2.0]heptane framework) takes place to give the phenylalanine derivatives 8a–g with remarkably high stereoselectivity (59–92% ee).

Synthesis of either enantiomer of cis-3-aminocyclopentanecarboxylic acid from both enantiomers of racemic 2-azabicyclo[2.2.1]hept-5-en-3-one

(–)-2-Azabicyclo[2.2.1]hept-5-en-3-one (–)-1 was converted into (–)-cis-3-aminocyclopentanecarboxylic acid (–)-2 in two steps and into the enantiomeric amino-acid (+)-2 in three steps.

Preparation of carbocyclic analogues of 2′-deoxyribonucleotides possessing a phosphonate substituent at the 5′-position

The epoxycyclopentanol 10 is converted into the methylphosphonate 15 in 30% overall yield. The diol 15 is converted into the protected carbocyclic nucleotide mimics 16, 18, 21 and 22 in 38–70% yield. The diol 15 is resolved using a lipase-catalysed esterification and the absolute configurations of the enantiomers are deduced by CD spectroscopy.