Photolysis for Vitamin D Formation. Supporting Information

Transcription

1 S1 Synthesis of 1α-Hydroxyvitamin D 5 Using a Modified Two Wavelength Photolysis for Vitamin D Formation Supporting Information Robert M. Moriarty and Dragos Albinescu Spectra C: 3β-Acetoxy-stigmasta-5,7-diene 8 S C: 9, 10-seco-Stigmasta-5(Z),7(E),10(19)-trien-3β-ol 13 S C: SO 2 Adduct of 9,10-seco-stigmasta-5(Z),7(E),10(19)-trien-3β-ol 14 S C: 9, 10-seco-Stigmasta-5(E),7(E),10(19)-trien-3β-ol 15 S C: 3β-Triethylsilyloxy-9,10-seco-stigmasta-5(E),7(E),10(19)-triene 16 S C: 1α-Hydroxy-3β-triethylsilyloxy-9,10-seco-stigmasta-5(E),7(E),10(19)-triene 17 S C: 1α-Hydroxy-3β-triethylsilyloxy-9,10-seco-stigmasta-5(Z),7(E),10(19)-triene 18 S H: 1α, 3β-Dihydroxy-9,10-seco-stigmasta-5(Z),7(E),10(19)-triene 1 S C: 1α, 3β-Dihydroxy-9,10-seco-stigmasta-5(Z),7(E),10(19)-triene 1 S10 Experimental 1. (24S)-3β-Tosyloxy-stigmasta-5, 22(E)-diene 7 S β-Methoxy-3α, 5-cyclo-5α-stigmast-22(E)-ene 8 S β-Methoxy-3α, 5-cyclo-5α-stigmastane 9 S β-Triethylsilyloxy-9, 10-seco-stigmasta-5(E), 7(E), 10(19)-triene 17 S12

2 S2 13 C-NMR Spectrum of 3β-acetoxy-stigmasta-5,7-diene 8 AcO

3 S3 13 C-NMR Spectrum of 9,10-seco-stigmasta-5(Z),7(E),10(19)-trien-3β-ol 13 HO

4 S4 13 C-NMR Spectrum of SO 2 adduct of 9,10-seco-stigmasta-5(Z),7(E),10(19)-trien-3β-ol 14 H SO 2 HO

5 S5 13 C-NMR Spectrum of 9,10-seco-stigmasta-5(E),7(E),10(19)-trien-3β-ol 15 OH

6 S6 13 C-NMR Spectrum of 3β-triethylsilyloxy-9,10-seco-stigmasta-5(E),7(E),10(19)-triene 16 OTES

7 S7 13 C-NMR Spectrum of 1α-hydroxy-3β-triethylsilyloxy-9,10-seco-stigmasta-5(E),7(E),10(19)-triene 17 HO OTES

8 S8 13 C-NMR Spectrum of 1α-hydroxy-3β-triethylsilyloxy-9,10-seco-stigmasta-5(Z),7(E),10(19)-triene 18 TESO OH

9 S9 1 H-NMR Spectrum of 1α,3β-dihydroxy-9,10-seco-stigmasta-5(Z),7(E),10(19)-triene 1 HO OH

10 S10 13 C-NMR Spectrum of 1α,3β-dihydroxy-9,10-seco-stigmasta-5(Z),7(E),10(19)-triene 1 HO OH

11 S11 Experimental (24S)-3β-Tosyloxy-stigmasta-5,22(E)-diene (7). To a stirred mixture of β-stigmasterol 6 (25 g, 60.6 mmol) in dichloromethane (100 ml) and pyridine (60 ml) at 0 C, p-toluenesulfonyl chloride (34.5 g, mmol) in dichloromethane (100 ml) was added dropwise followed by addition of 4- dimethylaminopyridine (0.37 g, 3.0 mmol). The reaction mixture was stirred overnight at room temperature, then water (300 ml) was added. The reaction mixture was cooled to 0 C, acidified to a ph of 3 with 6 M hydrochloric acid, and extracted three times with diethyl ether (200 ml each time). The ethereal extract was washed with water, 10% sodium bicarbonate and brine, dried over sodium sulfate, concentrated in vacuo, and the resulted solid was recrystallized from acetone, to yield the tosylate 7 (29.4 g, 80%) as white needles. mp C (lit C). 6β-Methoxy-3α,5-cyclo-5α-stigmast-22(E)-ene (8). p-toluenesulfonate 7 (29 g, mmol) as a fine powder, was added to a solution of anhydrous potassium acetate (81.4 g, 829 mmol) in dry methanol (2.0 L) and the stirred mixture was refluxed for 6 hours, under argon. After reflux, the cold slurry was evaporated in vacuo and the residue was partitioned between ether and water. The ether layer was washed with 5% solution of sodium bicarbonate, then with water and brine. Drying of the ethereal extract over anhydrous sodium sulfate and evaporation of the solvent, yielded an oily material that was chromatographed on silica gel (hexanes:ethyl acetate 9:1) to give the desired derivative (17.5 g, 80%) as a soft, crystalline solid. mp C (lit C, from acetone-water). 6β-Methoxy-3α,5-cyclo-5α-stigmastane (9). A mixture of 8 (17.3 g, 41 mmol) in ethyl acetate (250 ml) and 10% palladium on charcoal (4 g), was stirred under a hydrogen atmosphere for 16 hours. The reaction mixture was filtered through celite and the solvent was evaporated under reduced pressure to give g of 9 (100% by 1 H- and 13 C-NMR) as an oil 7, which was used in the next step without any other purification.

12 S12 3β-Triethylsilyloxy-9,10-seco-stigmasta-5(E),7(E),10(19)-triene (17). A solution of 16 (2.24 g, 5.43 mmol) in dichloromethane (35 ml) and dimethylformamide (15 ml) was treated with diisopropylethylamine amine (1.9 ml, mmol) and triethylsilyl chloride (1.4 ml, 1.23 mmol). The reaction mixture was stirred at room temperature for 1 hour and then the reaction was quenched with 1 M potassium carbonate. The aqueous phase was extracted three times with ethyl ether then the organic phase was washed with water, brine and dried over anhydrous sodium sulfate. The residue obtained after solvent evaporation under reduced pressure, was chromatographed on silica gel using hexanes:ethyl acetate 95:5 as the eluent to yield the silylated derivative (2.8 g, 98%). IR (neat): 2950, 2875, 1631 (vw) 1458, 1373, 1234, 1074, 1007, 733 cm 1. 1 H-NMR (CDCl 3 ), δ (ppm): 3.81 (1H, m), 4.66 and 4.96 (2H, s), 5.88 (1H, d, J=11.4 Hz), 6.50 (1H, d, J=11.4 Hz). 13 C-NMR (CDCl 3 ), δ (ppm): 149.9, 144.2, 136.3, 120.2, 116.2, 107.9, 69.8, 56.7, 56.7, 46.1, 46.0, 40.8, 38.1, 36.7, 35.7, 34.1, 31.8, 29.4, 29.2, 27.9, 26.3, 23.8, 23.3, 22.4, 20.0, 19.2, 19.1, 12.3, 12.2, 7.1, 5.1. MS m/z 526 (M + ) for C 35 H 62 OSi. HRMS found: ; calc.: