Malcolm M. Campbell

Aminophosphonic and aminophosphinic acid analogues of aspartic acid

Abstract 4-Oxoazetidin-2-ylphosphonates and phosphinates, obtained from Arbusov reactions of 4-acetoxyazetidin-2-one and 4α-acetoxy-3β-phthalimido-2-one with a variety of phosphites and phosphonites, were hyrdolysed to β-phosphono- and β-phosphino β-alanine (phosphono- and phosphinoaspartic acid) derivatives. In model studies for their incorporation in peptides, conditions for the selective removal of protecting groups for carboxylic acids, phosphonic and phosphinic acids, and amines, in derived di- and tri-peptides were investigated. Alanyl and alanyl alanyl peptide incorporation into bacteria was studied.

A novel and convenient synthesis of bis[arylthio]methanes

Abstract Bis[arylthio]methanes are produced in high yield on treatment of aryl chloromethyl sulphides with neutral alumina.

New reaction of penicillins: the formation, and crystal and molecular structure of a β-lactam-fused heterocyclic ylide

The formation and X-ray crystallographic structure of the ylide (3) derived from reaction of chloramine T with methyl 6β-phenylacetamidopenicillanate are reported.

Conversion of 6α-alkoxyformamidopenicillanates into 6α-aminopenicillanates, and the formation of 6-spiropenicillanates

Methyl 6β-phenoxyacetamido-6α-trichloroethoxyformamidopenicillanate has been converted into a 6α-aminopenicillanate; 6α-ethoxyformamido-6β-phenoxyacetamidopenicillanates reacted with phosgene and base to afford unique (1-ethoxycarbonyl-3-phenoxyacetyl-2-oxo-1,3-diazetidine)-4-spiro-6′-penicillanates.

Formation of enantiomeric 4-oxa-2,6-diazabicyclo[3.2.0]hept-2-en-7-ones from methyl 6α- and 6β-phenoxyacetamidopenicillanates

Methyl 6α-phenoxyacetamidopenicillanate was transformed by reaction with chloramine T or (dichloroiodo)-benzene into methyl 3-methyl-2-[(1R,5S)-3-phenoxymethyl-7-oxo-4-oxa-2,6-diazabicyclo[3.2.0]hept-2-en-6-yl]but-2-enoate. The (1S,5R)-isomer was prepared by the reaction of (dichloroiodo)benzene with methyl 6β-phenoxyacetamidopenicillanate. Differences in the reactivities of the 6α- and 6β-acylaminopenicillanates towards chloramine T and (dichloroiodo)benzene are noted.

Conversion of secopenicillanic acid derivatives into β-lactam sulphimides and oxazolines

4-(Methylthio)azetidin-2-ones when treated with chloramine T gave in each case a single sulphimide enantiomer, together with both possible sulphoxides. The sulphimides were readily converted by heating, or by attempted oxidation or reduction, into β-lactam fused oxazolines. The 4-methylthio-3-(triphenylmethylamino)azetidin-2-one derivative did not undergo comparable reaction with chloramine T.

A new route to 6,6-disubstituted penams and 7,7-disubstituted cephems

The reaction of penicillanate esters with N-chloro-N-sodiourethane gave 6,6-diacylaminopenicillanates from which the corresponding 7,7-diacylaminodeacetoxycephalosporanates were prepared via the sulphoxides.

Michael additions to steroidal 1-ene-3-ones

Abstract A reactivity pattern was established for Michael addition of aryl thiolates to 17-acetoxy 5α-androst-1-en-3-one. An abnormal bicyclic bridged adduct was obtained in the reaction of thiourea.

Transformations of penicillins: reactions with chloramine T

Reaction of chloramine T trihydrate with certain 6β-amidopenicillanates affords β-lactam-fused thiadiazine S-imides. The structure of one S-imide was established by X-ray crystallography and those of the others were deduced by spectroscopic comparison. Penicillanates lacking a secondary amide group at C-6 did not undergo comparable reaction. The β-lactam-fused heterocyclic S-imides were particularly stable towards a series of reactants, including oxidising and reducing reagents. Trichloroethyl 6β-phenylacetamidopenicillanate was significantly different in its reactivity towards chloramine T, affording β-lactam-fused oxazolines and a monocylic chlorozetidinone. A by-product in these reactions was identified as NN′-thiobis(toluene-p-sulphonamide).

Cephalosporin sulphoxides: functionalization at C-2 and C-4

Deacetoxycephalosporanate (S)-1-oxide 2-anions afforded (a) the Michael adducts with acrylonitrile, (b) Pummerer reactions with alkoxychloroformates, and (c) diazo-exchange reactions with tosyl azide, whereas the (R)-oxide under similar conditions reacted only with acrylonitrile giving a Michael adduct at C-4.