John J. Wright

Mass spectral studies on aminocyclitol–aminoglycoside antibiotics

The electron impact mass spectral fragmentation patterns of a series of underivatized aminocyclitol–aminoglycoside antibiotics are reported, and their utility in making structural assignments is discussed. The compositions of the fragment ions were confirmed by high resolution mass measurements, and in some cases the origins of the ions were determined by the “direct analysis of daughter ions” technique. The chemical ionization mass spectra of representative compounds of this class are also reported. In general the mass spectra of the underivatized compounds, at least up to the pseudotrisaccharide size, were simpler to interpret and afforded more useful diagnostic information than those of their more volatile permethyl, trimethylsilyl, and per-N-aralkylidene derivatives studied by others.

Structural elucidation of heptaene macrolide antibiotics 67–121-A and 67–121-C

The total gross structures of two heptaene macrolide antibiotics of the aromatic subgroup have been determined.

Synthesis of 14-α-aminomethyl substituted lanosterol derivatives; inhibitors of fungal ergosterol biosynthesis

Several 14-α-aminomethyl-substituted lanosterol derivatives have been synthesized involving a complete Δ7,8to Δ8,9isomerization; these compounds are inhibitors of fungal ergosterol biosynthesis and are active against intact Candida and dermatophyte strains.

Synthesis of 3-amino-2,3-dideoxy-α-D-arabino-hexopyranosyl gentamine C1

Acid catalysed addition of 3-acetamido-3-deoxy-4,6-di-O-acetyl-D-glucal (2) to the relatively complex pseudodisaccharide (4) resulted in regio- and stereoselective formation of the 2-deoxy-α-glycoside (5).

Semisynthetic aminoglycoside antibacterials. Part 11. Solution conformations of semisynthetic and naturally occurring aminoglycoside antibiotics

A critical analysis of the 13C n.m.r. spectral data for a wide range of naturally occurring aminoglycoside antibiotics, as well as for a diverse assortment of semisynthetic aminoglycoside antibacterials, has revealed new insights into the solution conformation of these clinically important drugs. Correlation of the Δδc values for C-4 and C-6 determined in going from deoxystreptamine to the pseudo di-or tri-saccharides, as well as changes in the chemical shifts of C-1′ and C-1″, has revealed that these molecules adopt a wide range of well defined conformations in solution, that are dependent not only on the structure, but also the pH. The limitations of the ‘Nagabhushan–Daniels Rule,’ which has been reported to break down when applied to some classes of aminoglycosides, are discussed in the light of these new observations.