Calanolide → (-)-Inophyllum P

Participants

Reaction Steps

This example illustrates the preparation of antiviral 7,8-dihydro compounds (FIG. 6) of series 2, specifically 7,8-dihydrocalanolide A, 7,8-dihydrocalanolide B, 7,8-dihydro-costatolide, and 7,8-dihydrosoulattrolide from the corresponding 7,8-unsaturated compounds of series 1. Of these six compounds, only one structure (7,8-dihydrocostatolide; Stout, G. H., et al., J. Org. Chem., 29, 3604-3609 (1964)) had been previously reported, however none of the six were known heretofore to have antiviral activity. The 7,8-dihydro compounds were made by catalytic hydrogenation of the selected appropriate 7,8-unsaturated precursors. In a typical procedure, 10 mg of calanolide A was stirred with 2.5 mg PtO2 (Aldrich) in 4 ml MeOH under an atmosphere of H2 (a balloon filled with H2 was attached to the reaction vessel to provide a slightly positive pressure of H2) for 30 min. The mixture was filtered, and the solvent removed in vacuo to provide a light yellow oil which was purified by SiO2HPLC (21.1×300 mm, Dynamax column) eluted with 25 ml/min hexane/EtOAc (7:3) to give 9.0 mg of 7,8-dihydrocalanolide A (EIMS m/z 372, appropriate for C22H28O5 ; 1H NMR, see Table 5). In an exactly analogous fashion, 6 mg of calanolide B with 3 mg PtO2 in 4 ml MeOH was converted to 3.6 mg of 7,8-dihydrocalanolide B (EIMS m/z 372, appropriate for C22H28O5 ; 1H NMR, see Table 5); 100 mg of costatolide with 15 mg PtO2 in 20 ml MeOH was converted to 89.9 mg 7,8-dihydrocostatolide (EIMS m/z 372, appropriate for C22H28O5 ; 1H NMR, see Table 5); and 12 mg of soulattrolide with 3 mg PtO2 in 4 ml MeOH was converted to 8.9 mg 7,8-dihydrosoulattrolide (EIMS m/z 406, appropriate for C25H26O5 ; 1H NMR, see Table 5).

Provenance & Evidence