Calanolide → (-)-Inophyllum P

HRID 342698Notes

Reaction equation

HRID 342698 reaction equation
[CH3:1][CH2:2][CH2:3][C:4]1[C:10]2[C:11]3[O:25][C:24]([CH3:27])([CH3:26])[CH2:23][CH2:22][C:12]=3[C:13]3[O:18][C@@H:17]([CH3:19])[C@H:16]([CH3:20])[C@H:15]([OH:21])[C:14]=3[C:9]=2[O:8][C:6](=[O:7])[CH:5]=1.[CH3:28][CH2:29][CH2:30]C1C2C3OC(C)(C)C=CC=3C3OC(C)C(C)C(O)C=3C=2OC(=O)C=1>CO.O=[Pt]=O>[CH3:20][C@@H:16]1[C@H:15]([OH:21])[C:14]2[C:9]3[O:8][C:6]([CH:5]=[C:4]([C:3]4[CH:28]=[CH:29][CH:30]=[CH:1][CH:2]=4)[C:10]=3[C:11]3[O:25][C:24]([CH3:27])([CH3:26])[CH:23]=[CH:22][C:12]=3[C:13]=2[O:18][C@H:17]1[CH3:19])=[O:7]

Participants

5

Reactant 2

HCID 1201CalanolideHCID 65061Dihydrocostatolide

Product 1

HCID 72978(-)-Inophyllum P

Reagents, catalysts & solvents 2

HCID 345198Adams' catalystCatalystHCID 887MethanolSolvent

Procedure

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).

Workup

  1. additionfilled with H2
  2. customto provide a slightly positive pressure of H2) for 30 min
  3. filtrationThe mixture was filtered
  4. customthe solvent removed in vacuo
  5. customto provide a light yellow oil which
  6. customwas purified by SiO2HPLC (21.1×300 mm, Dynamax column)
  7. washeluted with 25 ml/min hexane/EtOAc (7:3)

Sources & evidence

ORD record
ord-a555ee34d19a4472a5b48cb935df6098
Source dataset
uspto-grants-1999_01
Patent number
US05859049

Reaction notes

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