Reaction Steps
To prepare 22, a solution of 3 (Srinivasan et al., PLoS Biol. 10:e1001237 (2012), which is hereby incorporated by reference in its entirety) (181.5, 413 μmol) in dry tetrahydrofuran (0.5 mL) was added to a mixture of LiOH (8.9 mg, 371 μmol) and water (0.2 mL) in 1,4-dioxane (1 mL). After stirring at 67° C. for 40 minutes the solution was acidified with few drops of glacial acetic acid and concentrated in vacuo. Flash column chromatography on silica using a gradient of 10-40% ethyl acetate in hexanes afforded 20 (48.5 mg, 145 μmol, 35%) as a colorless oil. A solution of 20 (48.5 mg, 145 μmol) in dry dichloromethane (2 mL) was treated with Dess-Martin periodinane (88 mg, 208 μmol). After 5 hours the solution was diluted with 10 mL dichloromethane and washed three times with a solution of 5% Na2S2O3 in H2O. The organic layer was dried over Na2SO4 and concentrated in vacuo. Flash column chromatography on silica using a gradient of 0-30% ethyl acetate in hexanes afforded 21 (26.8 mg, 81 μmol, 56%) as a colorless oil. A solution of 21 (24.5 mg, 74 μmol) in 1:1 dichloromethane:methanol (0.7 mL) was treated with NaBH4 (12 mg, 317 μmol). After 10 minutes the solution was acidified with glacial acetic acid and diluted with dichloromethane and concentrated in vacuo. Flash column chromatography on silica using a gradient of 0-40% ethyl acetate in hexanes afforded (2S,3R,5S,6R)-6-((R)-hex-5-en-2-yloxy)-5-hydroxy-2-methyltetrahydro-2H-pyran-3-yl benzoate (22) (18.2 mg, 54 μmol, 74%) as a colorless oil. 1H NMR (600 MHz, acetone-d6): δ (ppm) 8.04-8.01 (m, 2H), 7.67-7.63 (m, 1H), 7.55-7.50 (m, 2H), 5.89 (ddt, J=17.1 Hz, J=10.3 Hz, J=6.6 Hz, 1H), 5.09-5.04 (m, 1H), 4.99-4.95 (m, 1H), 4.84 (d, J=3.7, 1H), 4.69 (ddd, J=11.4 Hz, J=9.8 Hz, J=4.6 Hz, 1H), 4.04-3.98 (m, 1H), 3.89-3.82 (m, 1H), 3.78-3.71 (m, 1H), 2.29-2.16 (m, 3H), 1.93-1.86 (m, 1H), 1.79-1.72 (m, 1H), 1.65-1.58 (m, 1H), 1.19 (d, J=6.1 Hz, 3H), 1.16 (d, J=6.3 Hz, 3H). 13C NMR (151 MHz, acetone-d6): δ (ppm) 165.9, 139.6, 134.1, 131.1, 130.2, 129.5, 114.9, 96.4, 73.7, 72.9, 67.8, 66.8, 37.3, 34.3, 30.7, 19.5, 17.9. See FIGS. 94A-B.
