Supporting Information. Expeditious Construction of the DEF Ring System of Thiersinine B

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1 Supporting Information Expeditious Construction of the DEF Ring System of Thiersinine B Masaru Enomoto and Shigefumi Kuwahara* Laboratory of Applied Bioorganic Chemistry, Graduate School of Agricultural Science, Tohoku University, Tsutsumidori-Amamiyamachi, Aoba-ku, Sendai , Japan skuwahar@biochem.tohoku.ac.jp Contents General Information S2 Experimental Procedures and Characterization Data S2 S4 1 H and 13 C NMR spectra S5 S18 S1

2 General Information IR spectra were recorded by an FT/IR spectrometer using an ATR (ZnSe) attachment. 1 H NMR spectra were recorded at 400 or 600 MHz and 13 C NMR spectra were recorded at 100 or 150 MHz with TMS as an internal standard in CDCl 3. High-resolution MS data were obtained by operating in the EI or FAB mode. Column chromatography was performed using mesh silica gel. Solvents for reactions were distilled prior to use: THF and DME from Na and benzophenone; CH 2 Cl 2 from CaH 2 ; toluene and Et 2 from LiAlH 4. All air- or moisture-sensitive reactions were conducted under a nitrogen atmosphere unless otherwise stated. H 7 PivCl Et 3 N 80% Piv 6 Kt-Bu AllocCl Piv 13 Pd(PPh 3 ) 4 then DBU 56% from 6 Piv 8 (1S*,8aS*)-8a-Methyl-6-oxo-1,2,3,4,6,7,8,8a-octahydronaphthalen-1-yl 2,2-dimethylpropanoate (6). To a stirred solution of 7 (3.14 g, 17.2 mmol) in THF (30 ml) were added DMAP (0.421 g, 3.45 mmol), triethylamine (7.21 ml, 51.7 mmol) and pivaloyl chloride (6.37 ml, 51.7 mmol) at rt under N 2. After 3 days, the mixture was diluted with saturated aq NH 4 Cl and extracted with ethyl acetate. The extract was successively washed with saturated aq NaHC 3 and brine, dried (MgS 4 ), and concentrated in vacuo. The residue was chromatographed over Si 2 (hexane/ethyl acetate, 10:1) to give 4.10 g (90%) of 6 as a colorless oil: IR ν max 2948 (m), 1726 (s), 1670 (s); 1 H NMR δ 1.22 (9H, s), 1.30 (3H, s), (1H, m), (1H, m), (4H, m), (1H, m), (3H, m), 4.62 (1H, dd, J = 12.0, 4.4 Hz), 5.82 (1H, d, J = 2.0 Hz); 13 C NMR δ 16.6, 22.8, 26.6, 27.1, 31.8, 33.4, 33.9, 39.0, 40.5, 78.7, 125.7, 166.8, 177.5, 198.9; HRMS (FAB) m/z calcd for C 16 H 25 3 ([M+H] + ) , found (1S*,8aS*)-5-Allyl-8a-methyl-6-oxo-1,2,3,4,6,7,8,8a-octahydronaphthalen-1-yl 2,2- dimethylpropanoate (8). To a stirred solution of 6 (231 mg, mmol) in THF (10 ml) was added Kt-Bu (147 mg, 1.31 mmol) at 0 C under N 2, and the mixture was stirred for 30 min at rt. Alloc chloride (111 µl, 1.05 mmol) was then added, and the resulting mixture was stirred at 0 C for 10 min. The mixture was poured into saturated aq NH 4 Cl at 0 C and extracted with S2

3 Et 2. The extract was successively washed with water and brine, and dried (MgS 4 ). The mixture was filtered through a pad of Si 2, and the filter cake was washed with EtAc. The combined filtrate and washings were concentrated in vacuo to give crude 13, which was then dissolved in DME (4.0 ml). The solution was added to a mixture of Pd(PPh 3 ) 4 (202 mg, mmol) and PPh 3 (91.5 mg, mmol) in DME (4.5 ml) at 0 C under Ar, and the mixture was stirred for 20 min at 0 C. DBU (350 µl) was then added, and the resulting mixture was stirred for 45 min at rt. The mixture was poured into saturated aq NH 4 Cl aq at 0 C and extracted with Et 2. The extract was successively washed with water and brine, dried (MgS 4 ), and concentrated in vacuo. The residue was chromatographed over Si 2 (hexane/etac, 40:1) to give 145 mg (56%) of 8 as a colorless oil. The spectral data (IR, 1 H NMR, 13 C NMR, MS) of 8 obtained by this procedure were identical with those of the enone prepared through the Claisen route described in the text. Piv 5 Ac Ac s 4 NM 1-Me-AZAD NaCl, KBr 46% Piv H H 17 48% Piv 18 Ac 1-Me-AZAD PhI(Ac) 2 58% s 4 (3 eq), Py 21% (5% from 5) Piv 19 CH Piv 3 H H Ac (1S*,8aS*)-5-(4-Acetoxy-4-methyl-2,3-dioxopentyl)-8a-methyl-6-oxo-1,2,3,4,6,7,8,8aoctahydronaphthalen-1-yl 2,2-cimethylpropanoate (18). To a stirred solution of 5 (129 mg, mmol) in CH 3 CN/water (3.6 ml, 2:1) were added NM (74.5 mg, mmol) and a catalytic amount of s 4 at rt. After 3 h, the mixture was diluted with water and extracted with EtAc. The extract was successively washed with water and brine, dried (MgS 4 ), and concentrated in vacuo. The residue was chromatographed over Si 2 (hexane/etac, 4:1 2:1) to give 64.5 mg (46%) of 17 (diastereomeric mixture) as a slightly brown oil. To a mixture of 17 (4.8 mg, 0.011mmol), KBr (0.1 mg, mmol) and 1-Me-AZAD (ca. 0.1 mg) in CH 2 Cl 2 /saturated aq NaHC 3 (1:1, 0.4 ml) was added 8% aq NaCl (51 µl, mmol) at 0 C, and the mixture was vigorously stirred for 20 min at rt. The mixture was diluted with EtAc and water, and extracted with EtAc. The extract was successively washed with water S3

4 and brine, dried (MgS 4 ), and concentrated in vacuo. The residue was chromatographed over neutral Si 2 (hexane/etac, 6:1) to give 2.3 mg (48%) of 18 as a colorless oil: IR ν max 2973 (s), 1723 (s), 1671 (s); 1 H NMR δ 1.22 (9H, s), 1.33 (3H, s), (1H, m), (3H, s), (3H, s) (1H, m), (4H, m) 2.04 (3H, s), (1H, m), (3H, m), 3.88 (2H, s), 4.68 (1H, dd, J = 11.6, 4.4 Hz); 13 C NMR δ 17.5, 21.0, 22.6, 24.1, 24.2, 26.3, 27.2 (3C), 27.5, 32.8, 33.0, 33.9, 39.0, 41.2, 78.6, 82.1, 127.7, 163.2, 172.1, 177.6, 195.8, , ; HRMS (FAB) m/z calcd for C 24 H 35 7 ([M+H] + ) , found EDF ring model 3. To a stirred solution of 18 (11.4 mg, mmol) in Et 2 (1.0 ml) were added s 4 (20.3 mg, mmol) and pyridine (60 µl, mmol) at rt. After 1 h, saturated aq NaHS 3 was added, and the resulting mixture was stirred for 20 h at rt. The mixture was extracted with EtAc, and the extract was successively washed with water and brine, dried (MgS 4 ), and concentrated in vacuo. The residue was chromatographed over Si 2 (hexane/etac, 5:1) to give 2.6 mg (21%) of 3 as a crystalline solid. The melting point and spectral data (IR, 1 H NMR, 13 C NMR, MS) of 3 obtained by this procedure were identical with those of the spirocyclic compound prepared from 5 by the two-step sequence described in the text. (1S*,8aS*)-8a-Methyl-6-oxo-5-(2-oxoethyl)-1,2,3,4,6,7,8,8a-octahydronaphthalen-1- yl 2,2-dimethylpropanoate (19). To a stirred solution of 17 (14.6 mg, mmol) in CH 2 Cl 2 (0.5 ml) were added PhI(Ac) 2 (16.1 mg, mmol) and 1-Me-AZAD (0.2 mg, mmol) at 0 C under Ar. After being stirred for 2 h at rt, the mixture was poured into a mixture of saturated aq NaHC 3 and saturated aq Na 2 S 2 3, and extracted with Et 2. The extract was successively washed with water and brine, dried (MgS 4 ), and concentrated in vacuo. The residue was chromatographed over Si 2 (hexane/etac, 3:1) to give 5.9 mg (58%) of 19 as a colorless oil: IR ν max 3730 (m), 2975 (m), 1731 (s), 1670 (m); 1 H NMR δ 1.23 (9H, s), 1.33 (3H, s), (1H, m), (1H, m), (4H, m), (1H, m), (1H, m), (1H, dd, J = 10.0, 4.0 Hz), (1H, dd, J = 8.4, 4.0 Hz), 3.45 (1H, dd, J = 17.0, 1.6 Hz), 3.56 (1H, d, J = 17.0 Hz), 4.67 (1H, dd, J = 12.0, 4.8 Hz), 9.57 (1H, t, J = 1.6 Hz); 13 C NMR δ 17.6, 22.5, 26.3, 27.2 (3C), 27.7, 32.8, 33.0, 39.1, 40.7, 41.3, 78.5, 126.8, 164.3, 177.6, 197.2, 198.4; HRMS (FAB) m/z calcd for C 18 H 27 4 ([M+H] + ) , found S4

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