Molecular orbital studies on nucleoside Antibiotics. I. Conformation of C‐C linked antibiotics, formycin and showdomycin

Quantum-mechanical studies, using the PCILO method, have been carried out on the conformational properties of formycin (both neutral and protonated), formycin B, oxoformycin B, and showdomycin with respect to XCN (whether anti or syn) and ΦC4′-C5′ (whether gg, gt, or tg). The results indicate that for neutral formycin, FMB, and oxoformycin B, the intrinsically preferred conformation is syn for XCN associated with gg for ΦC4′-C5′, while for protonated formycin and showdomycin, an anti conformation for XCN associated with the gg conformation for ΦC4′-C5′ is favored. The results also indicate the high probability for neutral formycin to adopt an anti conformation and support the dual behavior of neutral formycin as proposed by Ward and coworkers in order to explain the anomalous properties of formycin nucleotides and polynucleotides. The PCILO predictions for OXOFMB agree well with the observed crystallographic conformation. For the other compounds, the crystallographic conformation is attributed to inter- and intramolecular hydrogen bonding and packing forces in the crystal. Recent nuclear magnetic resonance results on neutral formycin and FMB show that the intrinsically preferred conformation (syn, gg) is observed for these molecules in solution.