John R. Kalman

On the structure and mode of action of the antibiotic ristocetin A

The antibiotics ristocetin A and ristomycin A are shown to be identical. It is concluded that ristocetin A is constituted from six sugars and an aglycone portion based on (i) a bis-ether containing three benzenoid rings, (ii) a fragment which on hydrolysis affords a 2′,4,6-trihydroxybiphenyl-2,3′-diyldiglycinate derivative, (iii) a previously isolated fragment incorporating a biphenyl ether, and (iv) at least one (and perhaps two) moles of potential glycine from alkaline hydrolysis. An approximate molecular-weight determination (2 063 ± 5 Daltons) of the antibiotic by californium plasma desorption mass spectrometry, 13C, and 1H n.m.r. spectra, and functional group determinations, are consistent with the incorporation of the above structural units in a tetracyclic aglycone structure. A cellwall component analogue, acetyl-D-alanyl-D-alanine, forms with ristocetin A a complex whose dissociation [in (CD3)2SO solution at 40 °C] is slow on the 1H n.m.r. time scale.

The conformations of triostin A in solution

The two symmetrical conformations of triostin A in deuteriochloroform have been investigated by 1H n.m.r. spectroscopy. The occurrence of two conformations is rationalised as resulting from the reversal of chirality of the disulphide bond, which is postulated to exist as a rapidly interconverting mixture of several rotameric states. Analysis of the spectrum of the least polar conformer is consistent with the presence of an intramolecular hydrogen bond.

Solution conformations of two synthetic analogues of quinoxaline antibiotics

The solution conformations of two synthetic quinoxaline antibiotics (TANDEM and ELSERTA) have been determined by proton n.m.r. The parameters utilised include chemical shifts, coupling constants, and the temperature variation of NH chemical shifts (all in the solvents [2H]chloroform, [2H5]pyridine, and [2H6]dimethyl sulphoxide). The conclusions have then been checked and amplified by the measurement of nuclear Overhauser effects in CDCl3 solution to indicate proximities of the various protons. The structures deduced are compared with other conformationally detailed structures of quinoxaline antibiotics, and their relevance to DNA-binding studies is discussed.

Methyl radical expulsions occurring with kinetic energy release

Evidence is presented to show that a reaction channel exists for the addition of a methyl radical to the central carbon atom of a delocalised –[graphic omitted]–CH[graphic omitted]R–system (X = O or NH) requiring a kinetic energy of ca. 40 kJ mol–1, since the delocalisation energy is lost in the addition process.