A nuclear magnetic resonance study of the solution conformations of the antibiotic pseudomonic acid A

Abstract

The proton and carbon n.m.r. spectra of pseudomonic acid A (1) were assigned by two-dimensional (2D) n.m.r. methods. The solution conformations of the tetrahydropyran (thp) ring, and some of the side-chain bonds of (1) and its sodium salt (2), were very similar to those of the antibacterially inactive monic acid A (3). Thus the inactivity of (3) is due to the lack of the nonanoic acid side-chain rather than any conformational changes. In D₂O both (2) and (3) were shown to populate a previously undetected thp ring conformation. The crystal structures of three compounds related to (1), (2), and (3) displayed only some of the conformations adopted by (1)–(3) in solution. It was concluded that there is a great potential for n.m.r. data as well as X-ray data to be used as input for computer modelling of molecular shape.