Peter D. Edwards

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 and Binding Properties of a Macrocyclic Peptide Receptor

Synthetic receptors for peptides and amino acid derivatives are of considerable interest because of their direct relevance to many biological peptide–protein complexes, and may also lead, for example, to new biosensors, therapeutics and catalysts for peptide hydrolysis. Macrocycle 1 is a selective receptor for various dipeptide derivatives in chloroform, and most notably shows a strong preference for N-Cbz-β-alanyl amino acids over N-Cbz-β-alanyl lactic acids.

Modified synthesis and binding properties of a peptide receptor

Abstract Macrocyclic receptor 9 , has been prepared in homochiral form. The receptor shows selectivity for certain dipeptides, and most notably a strong preference for N -Cbz-β-alanyl amino acids over N -Cbz-β-alanyl lactic acids.

Boron trifluoride catalysed reactions of 2,2,2-trichloroethyl 6-diazopenicillanate with aromatic aldehydes: rearrangements via penam c(5)-c(6) bond cleavage.

Abstract The BF3·Et2O catalysed reactions of diazopenicillanate 1 with aromatic aldehydes provide 2,3-dihydrothiazolo[2,3-b][1,3]oxazin-5-ones 4 via C(5)-C(6) cleavage of 6-formyl-penicillanates 8.

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.

Cytotoxic compounds. Part XVII. o-, m-, and p-(Bis-2-chloroethylamino)phenol, p-[N-(2-chloroethyl)methylamino]phenol, NN-bis-2-chloroethyl-p-phenylenediamine, and NN-bis-2-chloroethyl-N′-methyl-p-phenylenediamine as sources of biologically active carbamates

New or improved syntheses are reported of the nitrogen mustards named in the title, and of methyl m-(bis-2-chloroethylamino)-p-hydroxybenzoate. By reactions of the amines with aryl chloroformates, or of the phenols with aryl isocyanates or with isocyanates derived from α-amino-esters, carbamates containing alkyl, chloro-, alkoxy-, hydroxy-, methoxycarbonyl, carboxy-, acetyl, and sulphamoyl groups are obtained. Some of these have shown marked anti-tumour activity. p-(Bis-2-chloroethylamino)phenyl chloroformate has been prepared; it provides an alternative route to mustard carbamates. Some carbamates of the lachrymator type have been synthesised from p-aminophenacyl chloride.

Reactions of 2,2,2-trichloroethyl 6-diazopenicillanate with aromatic aldehydes. X-Ray crystal structures of (3S,8aS)-2,2,2-trichloroethyl 2,3-dihydro-6-(4-methoxyphenyl)-2,2-dimethyl-5-oxo-5H,8aH-thiazolo[2,3-b][1,3]oxazine-3-carboxylate and (2S,5S)-2,2,2-trichloroethyl-4-formyl-2-(4-methoxyphenyl)-6,6-dimethyl-3-oxotetrahydro-1,4-thiazine-5-carboxylate

Treatment of 6-diazopenicillanate (1) with aromatic aldehydes in the presence of Lewis acids provides spiro epoxides, oxazinones, and thiazepines, the product distribution depending upon the particular aldehyde and Lewis acid catalyst used. The structure of the oxazinone (5) derived from 4-methoxybenzaldehyde, was established by an X-ray crystal structure determination. An explanation for the formation of these products is proposed, and 6-acylpenicillanate intermediates either isolated or trapped. The epoxidation of the oxazinone (5) by m-chloroperoxybenzoic acid provided the tetrahydrothiazine (29), identified by X-ray crystallography.

Cytotoxic compounds. Part XVI. Reactions of the bismethanesulphonates of 3-(N-methylanilino)propane-1,2-diol and of 2-(N-methylanilino)-propane-1,3-diol with nucleophiles

The products formed in the reactions of these bismethanesulphonates with various nucleophiles have been identified by n.m.r. spectroscopy. With methanol, both gave only the 1,2-dimethyl ether, but with sodium methoxide identical mixtures of the 1,2- and the 1,3-dimethyl ether were obtained from each. With potassium acetate, both gave identical mixtures of the 1,2- and the 1,3-diacetate. All these reactions proceeded under kinetic control, and the results reflect the variations in the preferred mode of attack on intermediate aziridinium ions. Reactions with sodium phenyl sulphide proceeded partly by direct displacement, not involving a cyclic ion.