Supporting Information

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1 Supporting Information Wiley-VC Weinheim, Germany

2 The Total Synthesis of Chlorotonil A Nicola Rahn and Markus Kalesse* Prof. Dr. M. Kalesse, Dr. N. Rahn, Institut für rganische Chemie, Leibniz Universität annover, Schneiderberg 1B, D annover, Germany, Fax: (+49) , Markus.Kalesse@oci.uni-hannover.de Contents I. Experimental Procedures II. Copies of spectra III. RTEP plot of compound 13 Triene 12 TBS Br PMB To a stirred solution of dibromoolefin 5 (0.61 g, 1.49 mmol) and vinyl boronic ester 6 (0.99 g, 2.98 mmol) in degassed TF/ 2 (20 ml/4.8 ml) was added tetrakis-(triphenylphosphine)-palladium(0) (89.3 mg, 77 µmol) and five minutes later thalliumethylate (179 µl, 2.53 mmol). After one hour the reaction mixture was diluted with MTB-ether (50 ml) and 1M NaS 4 (15 ml). The solid was removed by filtration through Celite. The organic layer was separated and the aqueous was extracted twice with MTB-ether (20 ml). The combined organic layers were dried over MgS 4, filtered and concentrated in vacuo. Purification via column chromatography (hexane/ethyl acetate 20:1) yielded triene 12 (0.61 g, 1.13 mmol, 76%) as a colorless oil. 1 -NMR (400 Mz, CDCl 3 ): δ 7.28 (d, J = 8.6 z, 2), 6.90 (d, J = 8.6 z, 2), 6.09 (d, J = 14.9 z, 1), 6.01 (dd, J = 14.9, 6.9 z, 1), 5.81 (t, J = 7.1 z, 1), 5.00 (d, J = 9.4 z, 1), 4.48 (s, 2), 3.83 (s, 3), (m, 4), 3.12 (dd, J = 15.3, 7.2 z, 1), 3.03 (dd, J = 15.3, 7.0 z, 1), (m, 2), 1.72 (d, J = 1.3 z, 3), 1.09 (d, J = 6.8 z, 3), 0.96 (d, J = 6.7 z, 3), 0.90 (s, 9), 0.95 (s, 6); 13 C-NMR (100 Mz, CDCl 3 ): δ , , , , , , , , , , 75.87, 73.94, 69.44, 56.56, 38.02, 36.85, 36.04, 27.31, 25.01, 19.71, 18.89, 18.44, -3.92, -3.96; RMS: found [M- t butyl] +, calc. for C Si 1 Br 1 : ; [α] 25 D = -8.6 (c 1.03, CCl 3 ). 1

3 Synthesis of the alcohol 24 Br PMB 24 To a solution of 12 (370 mg, 0.69 mmol) in TF/pyridine (1:1, 22.8 ml) was added F*pyridine (70%, 7.8 ml) at RT, and the resulting mixture was stirred for 5 min at RT, and then quenched with saturated NaC 3 (7.8 ml). EtAc (15 ml) and phosphat buffer (7.8 ml, p 7) were added and the residue was extracted with EtAc. The combined organic extracts were dried over MgS 4, concentrated under reduced pressure and chromatographed on silica gel (hexane/ethyl acetate 2:1) to yield the alcohol 24 (280 mg, 0.66 mmol, 96%) as a colorless oil: [α] 20 D +6.4 (c 1.00, CCl 3 ), 1 -NMR (400 Mz, CDCl 3 ) δ = 7.28 (d, J = 8.6 z, 2), 6.90 (d, J = 8.6 z, 2), 6.09 (d, J = 14.8 z, 1), 6.01 (dd, J = 14.8, 6.8 z, 1), 5.82 (t, J = 7.3 z, 1), 5.00 (d, J = 9.56 z, 1), 4.47 (s, 2), 3.32 (s, 3), 3.50 (dd, J = 10.6, 5.8 z, 1), (m, 3), 3.14 (dd, J = 15.0, 7.2 z, 1), 3.07 (dd, J = 15.02, 7.3 z, 1), (m, 1), (m, 1), 1.77 (d, J = 1.0 z, 3), (br s, 1), 1.09 (d, J = 6.8 z, 3), 0.97 (d, J = 6.8 z, 3); 13 C-NMR (100 Mz, CDCl 3 ); δ = 159.1, , 130.2, 129.2, 129.2, 128.8, 126.0, 113.8, 74.5, 72.6, 67.9, 55.3, 36.7, 35.7, 34.8, 23.9, 17.3, 17.1; RMS calcd for C Br 1 : , found: Synthesis of the aldehyde 25 Br PMB 25 Dess-Martin periodinane (103 mg, 244 µmol) was added to the solution of alcohol 24 (86 mg, 203 µmol) in dry C 2 Cl 2 (2.7 ml) at RT. The resulting mixture was stirred for 1 h at RT and then quenched by addition of a solution of Na 2 S 2 3 *5 2 (143 mg) in saturated NaC 3 (1.3 ml). After being stirred for an additional 1 h at RT, the mixture was extracted three times with C 2 Cl 2. The combined organic extracts were washed with brine, dried over MgS 4 and concentrated under reduced pressure. The residue was purified by column chromatography (hexane/ethyl acetate 10:1) yielding the pure product 25 (74.47 mg, µmol, 87%) as colorless oil: [α] 20 D (c 1.00, CCl 3 ); RMS calcd for C Br 1 : , found

4 Ester 4 Et Br PMB To a stirred solution of aldehyde (68 mg, 161 µmol) in C 2 Cl 2 (3 ml) was added (triphenylphosphanylidene)-acetic acid ethyl ester (112.4 mg, 322 µmol). After two hours the solvent was removed in vacuo. Purification via column chromatography (hexane/ethyl acetate 10:1) yielded ester 4 (70.6 mg, 144 µmol, 89%) as a colorless oil. 1 -NMR (400 Mz, CDCl 3 ): δ 7.28 (d, J = 8.5 z, 2), 6.90 (dd, J = 14.0, 7.9 z, 1), 6.89 (d, J = 8.5 z, 2), (m, 2), (m, 2), 5.05 (d, J = 9.2 z, 1), 4.47 (s, 2), 4.20 (q, J = 7.2 z, 2), 3.82 (s, 3), (m, 3), 3.09 (dd, J = 15.4, 7.0 z, 1), 3.01 (dd, J = 15.4, 7.2 z, 1), 2.62 (qui, J = 6.7 z, 1), 1.75 (s, 3), 1.31 (t, J = 7.2 z, 3), 1.14 (d, J = 6.1 z, 3), 1.09 (d, J = 6.8 z, 3); 13 C-NMR (100 Mz, CDCl 3 ): δ , , , , , , , , , , , , , 74.54, 72.64, 60.22, 55.26, 36.69, 35.31, 34.63, 23.70, 20.25, 17.10, 14.30; RMS: found [M] + 25, calc. for C Br 1 : ; [α] D = (c 1.01, CCl 3 ). Lactone 13 Br Ester 4 (100 mg, mmol) was dissolved in toluene (50 ml) and treated with BF 3 *Et 2 (0.05 ml) at RT. Five minutes later PMB-deprotection was complete and the reaction mixture was heated in a sealed tube at 85 C for three hours. After cooling to RT it was washed with sat. NaC 3 -solution (10 ml). The organic layer was separated and the aqueous was extracted twice with MTB-ether (20 ml). The combined organic layers were dried over MgS 4, filtered and concentrated in vacuo. Purification via column chromatography (hexane/ethyl acetate 10:1) yielded lactone 13 (38.4 mg, mmol, 58%) in a diastereomeric ratio of 13:1 as a colorless solid. The diastereomers were separated by recrystallisation from Me. 1 -NMR (400 Mz, CDCl 3 ): δ 6.21 (dd, J = 5.3, 2.2 z, 1), 5.20 (s, 1), 4.42 (dd, J = 11.3, 5.3 z, 1), 3.92 (dd, J = 11.3, 9.2 z, 1), 2.65 (dd, J = 10.2, 5.5 z, 1), (m, 3), (m, 1), (m, 1), 1.81 (t, J = 13.7 z, 1), 1.72 (s, 3), 1.66 (q, J = 10.0 z, 1), 1.09 (d, 3

5 J = 6.5 z, 3), 0.94 (d, J = 6.5 z, 3); 13 C-NMR (100 Mz, CDCl 3 ): δ , , , , , 73.60, 45.26, 44.71, 44.38, 42.71, 36.41, 34.37, 31.73, 23.37, 21.65, 15.57; RMS: found [M] +, calc. for C Br 1 : ; [α] 25 D = (c 1.08, CCl 3 ). Synthesis of lactone To a solution of 13 (100 mg, 0.31 mmol) in methanol (18 ml) was added in small portions Na/g (5%, 3.0 g) at RT. The mixture was stirred for 2 h and quenched with MTB ether (270 ml). The resulting solution was washed successively with hydrochloric acid (1 M), saturated Na 2 S 4 and water. The organic layers were dried over MgS 4 and the solvent was removed under reduced pressure. The crude product was purified by column chromatography (hexane/ethyl acetate 10:1) to give the desired product 26 (70.26 mg, 0.29 mmol, 92%) as colorless solid: [α] 20 D (c 1.00, CCl 3 ); 1 -NMR (400 Mz, CDCl 3 ) δ = 5.74 (ddd, J = 9.9, 4.1, 2.4 z, 1), 5.67 (d, J = 9.9 z, 1), 5.20 (s, 1), 4.41 (dd, J = 11.3, 5.1 z, 1), 3.95 (dd, J = 11.3, 9.2 z, 1), 2.61 (dd, J = 9.9, 6.1 z, 1), (m, 1), (m, 1), (m, 2), 1.99 (dd, J = 16.6, 4.3 z, 1), 1.79 (t, J = 14.3 z, 1), 1.70 (s, 3), 1.43 (q, J = 9.9 z, 1), 1.09 (d, J = 6.8 z, 3), 0.94 (d, J = 6.8 z, 3); 13 C-NMR (100 Mz, CDCl 3 ) δ = 174.8, 133.8, 131.6, 128.2, 126.9, 73.3, 45.6, 42.5, 40.6, 38.6, 36.4, 34.4, 32.9, 23.4, 21.4, 15.9; RMS calcd for C : , found: Synthesis of aldehyde 21 Me 21 To the lactone 26 (35 mg, 143 µmol) was added a solution of K (400 mg) in methanol (4 ml). After stirring for 30 min at RT the formation of the hydroxyl acid was complete and methanol was removed under reduced pressure. The solid was dissolved in water (25 ml) and treated with hydrochloric acid (1 M) until the p of 4-5 was obtained. The mixture was extracted several times with EtAc and the 4

6 combined organic layers were dried over MgS 4 and concentrated under reduced pressure. A solution of diazomethane in diethyl ether was immediately added to the white residue until the solution becomes yellow. C 2 Cl 2 (1 ml) was then added to the reaction mixture and diethyl ether and the excess of diazomethane were removed under reduced pressure. To the remaining solution was added Dess-Martin periodinane (30% solution in C 2 Cl 2, 1 ml). After stirring for 30 min at RT, a solution of Na 2 S 2 3 *5 2 (50 mg) in saturated NaC 3 (0.5 ml) was added to the mixture and stirred for an additional 1 h at RT. The mixture was extracted three times with C 2 Cl 2. The combined organic extracts were washed with brine, dried over MgS 4 and concentrated under reduced pressure. The residue was purified by column chromatography (hexane/ethyl acetate 10:1) yielding the pure product 21 (30.4 mg, 110 µmol, 77%) as colorless oil: [α] 20 D (c 1.00, CCl 3 ); 1 -NMR (400 Mz, CDCl 3 ) δ = 9.70 (s, 1), 5.77 (dt, J = 9.7, 2.0 z, 1), 5.59 (dq, J = 9.7, 2.3 z, 1), 5.13 (s, 1), 3.65 (s, 3), (m, 1), (m, 2), (m, 3), 1.90 (t, J = 15.4 z, 1), 1.70 (s, 3), 1.44 (q, J = 9.4 z, 1), 1.16 (d, J = 7.2 z, 3), 0.92 (d, J = 6.8 z, 3); 13 C-NMR (100 Mz, CDCl 3 ) δ = 203.7, 175.8, 133.8, 132.9, 128.8, 126.1, 51.5, 47.9, 47.7, 43.9, 37.8, 37.7, 37.0, 36.4, 23.2, 20.9, 12.2; RMS calcd for C : , found: Synthesis of the PMB ester PMB Et To a mixture of (S)-(-)-lactic acid ethyl ester (7 g, mmol) in C 2 Cl 2 (170 ml) were added PMBtrichloroacetimidate (25.13 g, 88.9 mmol) and camphorsulfonic acid (1.38 g, 5.9 mmol). The resulting solution was stirred for 16 h at RT, while a white precipitate was formed. The solid was filtered off and washed with saturated NaC 3 solution. The filtrate was extracted with MTB ether and the organic layer was dried over MgS 4, filtered and evaporated. The residue was dissolved in hexane, the formed white precipitated was filtered and the solvent evaporated. The crude product was purified by flash chromatography (hexane/ethyl acetate 8:1) to give the pure product as colorless oil (13.7 g, 57.54, mmol, 97%): [α] 20 D (c 1.00, CCl 3 ); 1 -NMR (400 Mz, CDCl 3 ) δ 7.28 (d, J = 8.5 z, 2), 6.91 (d, J = 8.5 z, 2), 4.64 (d, J = z, 1), 4.44 (d, J = z, 1), 4.12 (q, J = 7.2 z, 2 ), 3.86 (s, 3), (m, 1), 1.30 (t, J = 7.2 z, 3), 1.13 (d, J = 6.09 z, 3); 13 C-NMR (100 Mz, CDCl 3 ) δ , , , , , 78.54, 72.66, 59.83, 56.02, 15.90, 13.61; RMS calcd for C : , found Synthesis of the PMB alcohol 5

7 Synthesis of the PMB alcohol PMB To a cooled (-78 C) solution of the ester (10 g, mmol) in dry C 2 Cl 2 (126 ml) was added dropwise DIBAl- (1.5 M in toluene, 84 ml, mmol). The mixture was stirred for 1.5 h at -78 C, diluted with MTB ether and warmed up to RT, before water (11.5 ml) was slowly added. After 5 min a white gel was formed and Na (4 N, 11.5 ml) was added and the mixture was stirred for additional 1h at RT. The mixture was dried over MgS 4, filtered and the solvent evaporated under reduced pressure. Column chromatography on silica gel (hexane/ethyl acetate 5:1) yielded the desired product as colorless oil (7.08 g, mmol, 86%): [α] 20 D (c 1.00, CCl 3 ); 1 -NMR (400 Mz, CDCl 3 ) δ 7.29 (d, J = 8.5 z, 2), 6.90 (d, J = 8.5 z, 2), 4.60 (d, J = z, 1), 4.44 (d, J = z, 1), 3.83 (s, 3), (m, 2), (m, 1) 1.30 (t, J = 7.2 z, 3), 2.12 (br s, 1), 1.19 (d, J = 6.14 z, 3); 13 C-NMR (100 Mz, CDCl 3 ) δ , , , , 75.28, 70.51, 66.40, 55.37, 15.89; RMS calcd for C : , found Synthesis of the PMB aldehyde PMB xalylchloride (0.56 ml, 6.38 mmol) was dissolved in C 2 Cl 2 (14.9 ml), cooled at -78 C and treated with DMS (0.68 ml, 9.57 mmol). After 30 min, alcohol x1 (626 mg, 3.19 mmol) in C 2 Cl 2 (4.5 ml) was added and the mixture was stirred for 15 min at -78 C and for 1 h at -45 C, before Et 3 N (3.11 ml, mmol) was added and the reaction mixture was warmed to RT. A mixture (2:1) of MTB ether (70 ml) and saturated N 4 Cl solution (35 ml) was added and extracted with MTB ether. The organic layer was successively washed with saturated NaC 3 (25 ml) and brine (25 ml), dried over MgS 4 and filtered. The solvent was evaporated under reduced pressure and the product was used in the next step without purification: RMS calcd for C : , found Alkene 19 PMB 19 n-buli (2.5 M in hexane, 2.06 ml, 5.16 mmol) was dropwise added to a stirred suspension of methyltriphenylphosphonium bromide (2.88 g, 8.06 mmol) in dry TF (70 ml) at -78 C. The mixture was stirred for 30 min at -78 C and then for 30 min at RT. The yellowish ylide suspension is cooled 6

8 again to -78 C and the aldehyde was added slowly, the mixture was stirred for 5 min at this temperature and for 1 h at RT. Then aqueous N 4 Cl solution (27.8 ml/mmol MePh 3 PBr) was added, the resulting mixture was extracted with MTB ether (3x, 50 ml) and the combined organic extracts were dried over MgS 4. After evaporation of the solvent under reduced pressure, the residue was purified by flash chromatography on a silica gel (hexane/ethyl acetate 20:1) to give the product 19 (0.45 g, 2.33 mmol, 73%) as colorless oil: [α] 20 D (c 1.00, CCl 3 ); 1 -NMR (400 Mz, CDCl 3 ) δ 7.29 (d, J = 8.3 z, 2), 6.90 (d, J = 8.3 z, 2), 5.82 (ddd, J = 17.3, 10.2, 7.3 z, 1), (m, 2), 4.53 (d, J = 11.4 z, 1), 4.35 (d, J = 11.4 z, 1), (m, 1), 3.82 (s, 3), 1.30 (d, J = 6.1 z, 3); 13 C-NMR (100 Mz, CDCl 3 ) δ , , , , , , 75.94, 69.64, 55.20, 21.22; RMS calcd for C : , found Allyl phosphonate 18 P(C 2 CF 3 ) 2 18 Tris(2,2,2-trifuoro ethyl)phosphite (0.4 ml, 1.52 mmol), allyl bromide (0.25 ml, 3.05 mmol) and TBAI (30 mg) was heated to (180 C) for 24 h in a sealed vessel. The excess of allyl bromide was removed under reduced pressure and the residue purified by column chromatography (hexane/ethyl acetate 10:2) to afford the desired product 18 (0.27 g, 0.93 mmol, 61%) as colorless oil: 1 -NMR (400 Mz, CDCl 3 ) δ (m, 1), (m, 2), (m, 4), 2.78 (dd, J = 22.70, 7.34 z, 2); 13 C-NMR (100 Mz, CDCl 3 ) δ (d, J = 11.9 z), (qd, J = 277.6, 7.38 z), (d, J = 15.1 z), (qd, J = 37.8, 5.8 z), (d, J = z),) RMS calcd for C F 6 P 1 : , found Phosphonate 20 P(C 2 CF 3 ) 2 PMB 20 Phosphonate 18 (125 mg, µmol), alkene 19 (84 mg, µmol) and the Grubbs(II)-catalyst (16 mg, 21.9 µmol) were dissolved in dry C 2 Cl 2. After 16 h of refluxing (50 C) the solvent was evaporated under reduced pressure and the residue purified by column chromatography (hexane/ethyl acetate 2:1) yielding the pure product 20 as colorless oil (E/Z = 20:1): [α] 20 D (c 1.00, CCl 3 ); 1-7

9 NMR (400 Mz, CDCl 3 ) δ 7.24 (d, J = 8.9 z, 2), 6.90 (d, J = 8.9 z, 2), (m, 1), (m, 1), 4.47 (d, J = 11.3 z, 1), (m, 4), 4.31 (d, J = 11.3 z, 1), 3.92 (quid, J = 6.5, 2.4 z, 1), 3.80 (s, 3), 2.79 (dd, J = 23.4, 7.0 z, 2), 1.25 (d, J = 6.5 z, 3); 13 C-NMR (100 Mz, CDCl 3 ) δ , (d, J = 15.0 z), , , (qd, J = 276.8, 6.9 z), (d, J = 12.1 z), 113.8, (d, J = 2.3 z), 69.70, (qdd, J = 37.9, 6.2, 4.2 z),55.27, (d, J = z), 21.2 (d, J = 3.1 z); RMS calcd for C F 6 P 1 : , found Methyl ester 22 Me PMB To a stirred solution of phosphono ester 20 (128 mg, 285 µmol) in Et 2 (0.8 ml) at -80 C was added KMDS (0.5 M in Toluol, 0.17 ml, 87 µmol) dropwise. After 30 minutes aldehyde 21 (20 mg, 72 µmol) in Et 2 (0.53 ml) was added. ne and a half hour later the reaction mixture was transferred into sat. NaC 3 -solution (1.0 ml) and warmed to RT. The organic layer was separated and the aqueous was extracted twice with MTB-ether (2 ml). The combined organic layers were dried over MgS 4, filtered and concentrated in vacuo. Purification via column chromatography (hexane/ethyl acetate 20:1) yielded 22 (18.5 mg, 40 µmol, 55%) as a colorless oil in a 3:1 ratio of Z/E to E/E isomers. 1 -NMR (400 Mz, CDCl 3 ): δ 7.28 (d, J = 8.5 z, 2), 6.90 (d, J = 8.5 z, 2), 6.19 (dd, J = 15.5, 14.8 z, 1), 6.03 (dd, J = 14.8, 10.4 z, 1), 5.89 (d, J = 9.6 z, 1), 5.80 (d, J = 9.6 z, 1), 5.67 (dd, J = 15.5, 7.3 z, 1), 5.55 (dd, J = 15.2, 10.4 z, 1), 5.16 (s, 1), 4.5 (d, J = 11.4 z, 1), 4,33 (d, J = 11.4 z, 1), (m, 1), 3.83 (s, 3), 3.63 (s, 3), (m, 1), (m, 1), (m, 5), 1.69 (s, 3), (m, 1), 1.30 (d, J = 5.5 z, 3), 1.12 (d, J = 5.5 z, 3), 1.01 (d, J = 6.8 z, 3); 13 C-NMR (100 Mz, C 6 D 6 ): δ , , , , , , , , , , , , , , 75.19, 69.58, 54.53, 50.78, 48.97, 46.54, 42.89, 38.87, 38.30, 37.15, 23.05, 21.75, 20.85, 18.20; RMS: found [M] +, calc. for C : ; [α] 25 D = (c 1.00, CCl 3 ). 8

10 Synthesis of 23 PMB Et 23 To a suspension of Na (60%, 80 mg, 2.0 mmol) in TF (3 ml) at 0 C was added a solution of ethyl- 2-methylacetoacetate (0.32 ml, 2.0 mmol) in TF (2.3 ml). The resulting mixture was stirred for 1.5 h at RT and than cooled again at 0 C before a solution of n-buli (2.5 M in hexane, 0.8 ml, 2.0 mmol) was added. After stirring for 45 min at 0 C and for 30 min at RT, the reaction was cooled to -78 C, and the methyl ester 22 (46.46 mg, 0.10 mmol) in TF (0.9 ml) was added. After addition of the methyl ester, the reaction was stirred for 1 h at 0 C and warmed up to RT. When the methylester 22 is completely converted (TLC), 1 N sulfuric acid (1 ml) was added, the mixture was diluted with MTB ether and extracted with MTB ether five times (2 ml). The combined organic extracts were washed successively with water, saturated NaC 3, brine and dried over MgS 4. The solvent was removed under reduced pressure and the crude product was purified by column chromatography (hexane/ethyl acetate 10:1) to give 23, which however is still contaminated with ethyl-2-methylacetoacetat. RMS calcd for C : , found: Dehalogenated Chlorotonil A Diketo ester 23 (5.6 mg, 9.7 µmol) was dissolved in toluene (10 ml) and treated with BF 3 *Et 2 (10 µl). After 15 minutes NaC 3 -solution (0.5 ml) was added to the reaction mixture. The organic layer was separated and the aqueous was extracted twice with ethyl acetate (1 ml). The combined organic layers were dried over MgS 4, filtered and concentrated in vacuo. Purification via column chromatography (hexane/ethyl acetate 5:1) yielded dehalogenated chlorotonil A (3.0 mg, 7.3 µmol, 75%) as a colorless solid. 9

11 1 -NMR (400 Mz, CDCl 3 ): δ (s, 1), 6.20 (dd, J = 14.0, 11.2 z, 1), 5.81 (t, J = 10.4 z, 1), 5.70 (d, J = 10.4 z, 1), (m, 1), 5.50 (dq, J = 10.0, 2.1 z, 1), (m, 4), 4.59 (q, J = 6.6 z, 1), 3.39 (dd, J = 11.8, 7.1 z, 1), 2.92 (br s, 1), 2.70 (br s, 1), (m, 1), (m, 1), (m, 2), 1.77 (s, 3), (m, 1), 1.37 (d, J = 6.6 z, 3), 1.00 (d, J = 7.0 z, 3), 0.75 (d, J = 6.5 z, 3), 0.62 (d, J = 7.1 z, 3); 13 C-NMR (100 Mz, CDCl 3 ): δ , , , , , , , , , , , , 69.41, 48.25, 45.25, 41.45, 38.43, , 30.89, 30.66, 23.89, 20.47, 16.47, 15.50, 14.47; RMS: found [M+] +, calc. for C ; [α] 25 D = (c 1.02, CCl 3 ). Chlorotonil A (1) Cl Cl To a stirred solution of dehalogenated chlorotonil A (10 mg, 24.4 µmol) in C 2 Cl 2 (2 ml) were added 2,6-lutidine (2µL, 13.6 µmol) and NCS (6.83 mg, 51.2 µmol) at RT. After two hours the reaction mixture was diluted with ethyl ether (5 ml) and washed with sat. NaCl-solution (1 ml). The organic layer was separated and extracted twice with ethyl acetate (2 ml). The combined organic layers were dried over MgS 4, filtered and concentrated in vacuo. Purification via column chromatography (hexane/ethyl acetate 5:1) yielded chlorotonil A (1) (7.6 mg, 15.8 µmol, 65%) as a colorless solid. 1 -NMR (400 Mz, CDCl 3 ): δ 6.08 (t, J = 12.8 z, 1), 5.91 (t, J = 10.4 z, 1), 5.77 (d, J = 10.4 z, 1), (m, 1), (m, 2), (m, 1), 5.33 (t, J = 9.4 z, 1), 4.57 (q, J = 7.1 z, 1), 3.81 (dd, J = 11.8, 6.9 z, 1), 3.05 (br s, 1), 2.81 (br s, 1), 2.39 (br s, 1), (m, 2), 2.07 (d, J = 17.1 z, 1), (m, 1), 1.69 (s, 3), 1.68 (d, J = 7.1 z, 3), 1.35 (d, J = 6.8 z, 3), 0.98 (d, J = 6.5 z, 3), 0.87 (d, J = 7.2 z, 3); 13 C-NMR (100 Mz, CDCl 3 ): δ , , , , , , , , , , , 81.51, 70.25, 49.62, 47.03, 42.68, 38.29, 36.72, 33.32, 30.28, 30.13, 23.22, 20.92, 17.05, 15.64, 14.77; RMS: found [M+Na+MeCN] +, calc. for C N 1 Cl 2 Na 1 : ; [α] 25 D = (c 1.05, CCl 3 ). 10

12 11 Integral PMB C Mol. Wt.: 196,

13 PMB C Mol. Wt.: 196,

14 13 Integral PMB C Mol. Wt.: 192,

15 PMB C Mol. Wt.: 192,

16 F 3 C P CF 3 C 7 9 F 6 3 P Mol. Wt.: 286, Integral

17 F 3 C P CF 3 C 7 9 F 6 3 P Mol. Wt.: 286,

18 17 Integral F 3 C P CF 3 C F 6 5 P Mol. Wt.: 450, PMB

19 F 3 C 160 P PMB CF 3 C F 6 5 P Mol. Wt.: 450,

20 19 Integral TBS Br PMB C Br 3 Si Mol. Wt.: 537,

21 TBS Br PMB C Br 3 Si Mol. Wt.: 537,

22 Et 6.5 Br PMB C Br 4 Mol. Wt.: 491,

23 Et Br PMB C Br 4 Mol. Wt.: 491,

24 Br C Br 2 Mol. Wt.: 325,

25 Br C Br 2 Mol. Wt.: 325,

26 25 Integral C Mol. Wt.: 246,

27 C Mol. Wt.: 246,

28 27 Integral Me C Mol. Wt.: 276,

29 Me C Mol. Wt.: 276,

30 29 Integral Me PMB C Mol. Wt.: 464,

31 Me PMB C Mol. Wt.: 464,

32 31 Integral Integral C Mol. Wt.: 410,5458 dehalogenated Chlorotonil A

33 C Mol. Wt.: 410,5458 dehalogenated Chlorotonil A

34 Cl Cl C Cl 2 4 Mol. Wt.: 479,4359 Chlorotonil A (1) synthetic

35 Cl Cl C Cl 2 4 Mol. Wt.: 479,4359 Chlorotonil A (1) synthetic

36 Cl Cl C Cl 2 4 Mol. Wt.: 479,4359 Chlorotonil A (1) authentic sample

37 Cl Cl C Cl 2 4 Mol. Wt.: 479,4359 Chlorotonil A (1) authentic sample

38 RTEP polt of compound

39 RTEP plot of Chlorotonil A 38