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  • The synthesis route of strobol C

    2021-10-18

    The synthesis route of strobol C started from kirenol, which was treated with phosphomolybdic Amikacin australia hydrate in acetone to afford isopropylidenkirenol () as illustrated in . Treatment of with acetic anhydride in a mixture of dry pyridine, gave fully protected intermediate in 84.5% yields. Hydrolysis of in aqueous MeOH with trifluoroacetic acid (TFA, 1.2 equiv) afforded the desired 2, 19-diacetoxykirenol () in 86.0% yields. Oxidation of with sodium periodate in the aqueous of tetrahydrofuran (THF) gave the expected 2, 19-diacetoxy-pimarane-15-al () in 85% yields. Condensation of formyl group in the presence of a reducing agent of sodium borohydride in MeOH could afford the desired 12, 19-diacetoxy-15-hydroxy-16-norpimarane () in 78% yields, which could be transformed into strobol C () through the Wagnar-Meerwein rearrangement reaction enabled by methanesulfonyl chloride (The proposed mechanism was illustrated in )., The syntheses of strobol D and its intermediate products were achieved as shown in . The route was similar to that of strobol C. In summary, a six-step synthetic route to strobols C and D was designed, which was achieved using ordinary reagents. In this study, the formation of carbenium ion at C-15 mediated by MsCl, and the 1, 2-rearrangement of the carbenium ion were successfully accomplished to provide the corresponding strobane diterpenoids. All reaction steps were carried out by using conventional reagents. Consequently, this efficient and scalable methodology should be benefit for further the biological investigations on strobane diterpenoids. The structures of compounds and were established based on the interpretation of HRESIMS, 1D and 2D NMR data, and the analysis of chemical synthesis. The H NMR spectrum of () exhibited signals for an olefinic proton at 5.25 (1H, dd,  = 9.0, 5.2 Hz, H-15), and five methyl groups at 1.99 (3H, s), 1.16 (3H, s), 1.09 (1H, m), 0.79 (3H, s), 0.89 (3H, s), and 0.81 (3H, s). C NMR and DEPT data showed five methyl, seven methylene, four methine (including one olefinic carbon at 118.4 and one oxygenated at 80.4), three quaternary carbons (including one olefinic carbon at 141.9), one carbonyl carbon 170.8, and one oxygenated tertiary carbon at 75.1. In the HMBC spectrum, the cross-peaks from Me-17 (s) to C-13 ( 75.1), C-14, and C-12; and from H-15 ( 5.25) to C-7, C-9, C-13, and C-14, along with two proton spin systems of H-9/H-11/H-12 and H-14/H-15 in the COSY spectrum, demonstrated a unique seven-membered ring with a hydroxy group at C-13. In addition, the HMBC cross-peaks from Me-20 (s) to C-1, C-5, C-9, and C-10; and from Me-18 (s) to C-3, C-4, C-5, and C-19, together with the COSY correlations of H-1/H-2/H-3 and H-5/H-6/H-7. All these above characterized the structure of as a norstrobane diterpenoid. The relative configuration of C-13 was established on the basis of a NOESY experiment (). The correlations between Me-17, H-11a and H-9, and the correlations between OH-13 and H-15 rather than H-11 and H-9, indicated that the Me-17 at C-13 should be adopted -orientations. The structure of compound was determined using the same methord. Since species have been used to treat thromboembolic diseases as traditional Chinese medicine and previously isolated constituents from these species have been shown to have antithrombotic and anti-inflammatory activities,, compounds – were assessed for their antithrombotic potential by measuring the inhibitory effects on FXa (). The concentration of inhibitor required to inhibit the FXa activity by 50% under the assay conditions was defined as the IC value. Edoxaban was used as a positive control and gave an IC value of 3.4 ± 0.4 nM. The results presented are the mean values of three independent experiments. Compounds , , and showed significant activities with IC values of 1067 ± 164, 81 ± 11, 1023 ± 89 nM, respectively, and the other compounds showed weak or no effects in the same assay (IC > 2000 nM).