Allan G. Brown

Crystal and molecular structure of compactin, a new antifungal metabolite from Penicillium brevicompactum

The structure of compactin (I){7-[1,2,6,7,8,8a-hexahydro-2-methyl-8-(2-methylbutyryloxy)naphthyl]-3-hydroxyheptan-5-olide}, a metabolite isolated from cultures of Penicillium brevicompactum, has been determined by a combination of spectroscopic, chemical, and X-ray crystallographic methods.

Clavulanic acid, a novel β-lactam isolated from Streptomyces clavuligerus; X-ray crystal structure analysis

The structure of clavulanic acid, a β-lactamase inhibitor isolated from Streptomyces clavuligerus, has been shown by spectroscopic methods and X-ray analysis to be a novel fused β-lactam.

Structures of olivanic acid derivatives MM 4550 and MM 13902; two new, fused β-lactams isolated from Streptomyces olivaceus

The structures of two new, naturally occurring β-lactams are proposed on the basis of spectroscopic properties, and their interconversion.

The isolation and characterisation of (3R,5R)- and (3S,5R)-carbapenam-3-carboxylic acid from Serratia and Erwinia species and their putative biosynthetic role

Two new β-lactams (4b) and (5b), and (3S,5R)-carbapenam-3-carboxylic acid, have been isolated from strains of Serratia and Erwinia spp.; their possible role, and that of (5R)-carbapen-2-em-3-carboxylic acid as intermediates in the biosynthesis of the more complex members of the carbapenem family of β-lactam antibiotics is discussed.

Synthesis of diaryl ethers from tyrosine derivatives

Abstract Diaryl ethers of tyrosine, maintaining optical activity, have been formed through the reaction of a tyrosine derivative with an aryl iodonium salt.

SYNTHESIS OF ANALOGUES OF THE BIPHENOMYCIN ANTIBIOTICS

Abstract The oxidative coupling of L-tyrosine derivatives with vanadium oxyhalides has given dityrosine intermediates which were cyclized to give analogues of the biphenomycin antibiotics.

Synthesis of phenolically linked cyclic peptides

Abstract Cyclization of a diaryl ether containing an α, ω-amino acid residue leads to cyclic peptides which resemble the vancomycin binding pocket.

Clavulanic acid and its derivatives. Structure elucidation of clavulanic acid and the preparation of dihydroclavulanic acid, isoclavulanic acid, esters and related oxidation products

Clavulanic acid, a novel β-lactamase inhibitor from Streptomyces clavuligerus, has been shown to be Z-(2R,5R)-3-(β-hydroxyethylidene)-7-oxo-4-oxa-1 -azabicyclo[3.2.0]heptane-2-carboxylic acid (1). The structure and absolute stereochemistry was confirmed by X-ray analysis of the p-nitrobenzyl and p-bromobenzyl esters, (14) and (15). The conversion of clavulanic acid into a variety of esters and acyl derivatives is described. An account of its isomerisation to the E isomer (30) and the formation of an oxetane (45) as a by-product of the photolysis of the phenacyl ester (18) is given. The reduction and oxidation of acid (1) under a variety of conditions has also been examined in detail.

Application of the Suzuki biphenyl synthesis to the natural products biphenomycin and vancomycin

The synthesis of the unsymmetrical biphenyls 10 and 25 has been carried out by the palladium(0) catalysed coupling of the aryl boronic acid derivatives 5 and 20 with the aryl bromides 9 and 23 derived from (R)-4-hydroxyphenylglycine and (S)-tyrosine. In the former case unsuccessful attempts were made to bring about cyclization to compound 4 which is an analogue of the biphenyl ring system found in vancomycin. In the latter case, a variety of cyclization methods were used to give the cyclic products 34 and 35 which are analogues of the biphenomycin antibiotics.

Studies related to the structures of the olivanic acids MM 13902, MM 4550 and MM 17880 : Three β-lactam antibiotics from streptomyces olivaceus

Abstract MM 13902, a β-lactam antibiotic isolated from Streptomyces olivaceus, has been identified as (5R6R)- 3- [(E)- 2- acetamidoethenylthio]- 6- [(S)- 1- hydroxysulphonyloxyethyl]- 7- oxo- 1- azabicyclo [3.2.0] hept- 2- ene- 2- carboxylic acid (2) by chemical and spectroscopic studies. The related olivanic acids MM 4550 and MM 17880 have been shown to be the corresponding 3- [(E)- 2- acetamidoethenylsulphinyl]- and 3- (2- acetamidoethylthio)- derivatives (1 and 5), respectively. A number of carboxylate and sulphate esters of 1, 2 and 5 have been prepared. A key reaction in the characterisation of 2 was the oxidative degradation of its C-2 monomethyl ester (12) in dimethylsulphoxide to methyl 3 -[(E)- 2- acetamidoethenylthio]- 5- [(1R,2S)- 1- carboxy- 2- hydroxysulphonyloxyprop- 1- yl]pyrrole- 2- carboxylate (22). The configuration of the C-6 substituent of 2 was determined by a stereospecific elimination reaction of its ethyl sulphate, p-nitrobenzyl carboxylate (19) to yield the 6- (E)- ethylidene derivative (32). MM 13902 was oxidised to MM 4550 with m-chloroperbenzoic acid.