Supporting Information Unprecedented biological cyclopropanation in the biosynthesis of FR-900848 Tetsuo Tokiwano,* b Hiroaki Watanabe, a Takashi Seo a and Hideaki Oikawa* a a Division of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan. E-mail: [email protected]b Department of Biotechnology, Faculty of Bioresource Sciences, Akita Prefectural University, Akita 010-0195, Japan. E-mail: [email protected]General Unless otherwise noted, nonaqueous reactions were carried out under an argon atmosphere. Dichloromethane (CH 2 Cl 2 ), N,N-dimethylformamide (DMF) and tetrahydrofuran (THF) were dried over 4A molecular sieves. [ 2 H 4 ]methanol (99.8 atom% 2 H) and 2 H 2 O (99.9 atom% 2 H) were purchased from the Cambridge Isotope Lab. All other commercially supplied reagents were used as received. Optical rotations were recorded on a JASCO DIP-360 digital polarimeter. NMR spectra were obtained on a JEOL ECP-300, ECP-400, Alpha-400 and a Bruker AM-500 spectrometer for solutions of CDCl 3 . 1 H and 13 C chemical shifts were referenced to the solvent signals (7.26 and 77.0 ppm). Infrared (IR) spectra were obtained on a Hitachi 270-30 infrared spectrometer. High-resolution mass spectra (HR-MS) were obtained on a JEOL JMS-T100LP mass spectrometer (ESI). [4,4,4- 2 H 3 ]-1-(tert-butyldiphenylsilyloxy)-2-butyne (10). To a solution of 1-(tert-Butyldiphenylsilyloxy)-2-propyne (9, 4.02 g, 13.7 mmol) in THF (22 ml) was added dropwise a solution of BuLi (9.6 ml of a 1.56M solution in hexane, 15.0 mmol) at -78 °C. After stirring at 0 °C for 1 h, a solution of C 2 H 3 OTs (prepared from [ 2 H 4 ]methanol and TsCl, 3.36 g, 17.8 mmol) in THF (5.0 ml) was added. The resulting solution was stirred at 25 °C for 10 h. Then satd. NH 4 Cl (40 ml) was added, and the mixture was extracted with Et 2 O. The organic layers were washed with brine, dried over anhydrous Na 2 SO 4 , and concentrated in vacuo. The resulting residue was purified by flash chromatography (SiO 2 , hexane/EtOAc=100:1–50:1) to give 10 (4.06 g, 95%). 10: a colorless oil; 1 H-NMR (300 MHz, CDCl 3 ) δ 7.74-7.71 (4H, m), 7.44-7.26 (6H, m), 4.28 (2H, s), 1.07 (9H, s); 13 C-NMR (75 MHz, CDCl 3 ) δ 135.6, 133.3, 129.7, 127.6, 81.1, 77.5, 52.9, 26.7, 19.1; IR (film) 3072, 2932, 2856, 1474,1430, 1376, 1178, 1112, 998, 824, 738, 702, 612 cm -1 ; EI-HR-MS (positive) calcd for C 16 H 12 D 3 OSi [M–tBu] 254.1077, found m/z 254.1078. Thioester 14. To a solution of 10 (2.56 g, 8.20 mmol) in THF (40 ml) was added HF-pyridine (64 μl, 3.5 mmol). After stirring at 25 °C for 3 h, satd. NaHCO 3 (70 ml) was added. The resulting mixture was extracted with Et 2 O. The organic layers were dried over anhydrous Na 2 SO 4 , and concentrated in vacuo. The residue was purified by silica gel column
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Supporting - The Royal Society of Chemistry · Supporting Information Unprecedented biological cyclopropanation in the biosynthesis of FR-900848 Tetsuo Tokiwano,*b Hiroaki Watanabe,a
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Supporting Information
Unprecedented biological cyclopropanation in the biosynthesis of FR-900848 Tetsuo Tokiwano,*b Hiroaki Watanabe,a Takashi Seoa and Hideaki Oikawa*a
aDivision of Chemistry, Graduate School of Science, Hokkaido University, Sapporo 060-0810, Japan.
E-mail: [email protected] bDepartment of Biotechnology, Faculty of Bioresource Sciences, Akita Prefectural University, Akita 010-0195, Japan.