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. Author manuscript; available in PMC: 2017 Aug 26.
Published in final edited form as: Science. 2016 Aug 26;353(6302):912–915. doi: 10.1126/science.aag1028

Fig. 2. Complete synthetic sequence for the chemical synthesis of (+)-anhydroryanodol and (+)-ryanodol.

Fig. 2

Reagents and conditions as follows: 1. potassium hexamethyldisilazide (2.5 equiv), THF −78 °C; then 11 (2.4 equiv), 42-50% yield. 2. benzyl chloromethyl ether (5.0 equiv), iPr2NEt (8.0 equiv), nBu4NI (2.0 equiv), CH2Cl2, 50 °C, 65% yield. 3. Propynylmagnesium bromide, THF, 0 °C, 81% yield, 5:1 dr. 4. O3,/O2, CH2Cl2/MeOH (4:1), −78 °C; then PPh3, 91% yield. 5. Ethoxyethynylmagnesium bromide (5.0 equiv), THF, 0 °C, 75% yield. 6. AgOTf (2 mol %), PhMe, 0 °C, 90% yield. 7. CuI (3.0 equiv), vinylmagnesium bromide (6.0 equiv), THF, −78 to −30 °C, 84% yield. 8. [RhCl(CO)2]2 (1 mol %), CO (1 atm), m-xylene, 110 °C, 85% yield. 9. SeO2 (10 equiv), 4Å MS, 1,4-dioxane, 110 °C. 10. Comins' reagent, iPr2NEt, CH2Cl2, −78 to 0 °C, 28% yield, 2-steps. 11. PdCl2(PPh3)2, tributyl(prop-1-en-2-yl)stannane, LiCl, 2-MeTHF, 85 °C, 64% yield. 12. LiBH4, THF, −15 to −10 °C; then KHF2/MeOH. 13. H2, Pd(OH)2/C, EtOH, 61% yield, 2-steps. 14. Trifluoroacetic anhydride, urea hydrogen peroxide, Na2HPO4, 86% yield. 15. Li0 wire, NH3/THF, −78 °C, 38% yield.