M. Toufiqur Rahman, Jeffrey R. Deschamps, Gregory H. Imler, Alan W. Schwabacher and James M. Cook *

Transcription

1 SUPPORTING INFORMATION TOTAL SYNTHESIS OF MACROCARPINE D AND E VIA AN ENOLATE-DRIVEN COPPER- MEDIATED CROSS-COUPLING PROCESS: REPLACEMENT OF CATALYTIC PALLADIUM WITH COPPER IODIDE M. Toufiqur Rahman, Jeffrey R. Deschamps, Gregory H. Imler, Alan W. Schwabacher and James M. Cook * Department of Chemistry & Biochemistry, University of Wisconsin-Milwaukee, 3210 N Cramer Street, Milwaukee, WI-53211, United States Center for Biomolecular Science and Engineering, Naval Research Laboratory, Code 6930, Washington, D.C , United States ASEE Postdoctoral Fellow, Washington, DC * capncook@uwm.edu S1

2 TABLE OF CONTENTS 1. General Information S3 2. Experimental procedures and Analytical Data...S4 S9 3. Biogenetic Numbering of Compounds 4 and 5 S10 4. NMR ( 1 H and 13 C) Comparison Tables 1 & 2 for Natural and Synthetic Macrocarpine D (4) S11 5. NMR ( 1 H and 13 C) Comparison Tables 3 & 4 for Natural and Synthetic Macrocarpine E (5) S13 6. References...S14 7. Copies of NMR Spectra..S15 S27 8. X-ray Analysis Data for 22, 23, 23' and 19.S28 S51 9. Price comparison (Table 29) S52 S2

3 1. GENERAL INFORMATION All reactions were carried out under an argon atmosphere with dry solvents using anhydrous conditions unless otherwise stated. Tetrahydrofuran (THF) and diethyl ether were freshly distilled from Na/benzophenone ketyl prior to use. Dichloromethane was distilled from calcium hydride prior to use. Methanol was distilled over magnesium sulfate. Benzene and toluene were distilled over Na. Acetonitrile was distilled over CaH 2 prior to use. Reagents were purchased of the highest commercial quality and used without further purification unless otherwise stated. Thin layer chromatography (TLC) was performed on UV active silica gel, 200 μm, aluminum backed and UV active alumina N, 200 μm, F-254 aluminum backed. Flash and gravity chromatography were performed using silica gel P60A, μm, basic alumina (Act I, μm) and neutral alumina (Brockman I, ~150 mesh). TLC plates were visualized by exposure to short wavelength UV light (254 nm). Indoles were visualized with a 1% solution of ceric ammonium nitrate in 50% phosphoric acid. 1 H NMR data are reported as follows: chemical shift, multiplicity (brs = broad singlet, s = singlet, d = doublet, t = triplet, q = quartet, quin = quintet, dd = doublet of doublet, dt = doublet of triplet, ddd = doublet of doublet of doublets, td = triplet of doublets, qd = quartet of doublets, m = multiplet), integration, and coupling constants (Hz). 13 C NMR data are reported in parts per million (ppm) on the δ scale. The low resolution mass spectra (LRMS) were obtained as electron impact (EI, 70eV) and as chemical ionization (CI) using a magnetic sector (EBE) analyzer. HRMS were recorded by electrospray ionization (ESI) using a TOF analyzer, electron impact (EI) using a trisector analyzer and Atmospheric Pressure Chemical Ionization (APCI) using a TOF analyzer. S3

4 2. EXPERIMENTAL PROCEDURES AND ANALYTICAL DATA: General Procedure for Copper-Mediated cross-coupling reaction (preparation of 17/19/21/23) Condition 1 (Table 1, entries 1-4): In a sealed tube with a magnetic stir bar, a mixture of vinyl iodide 22 (1.0 mmol), CuI ( equiv), cis-1,2- cyclohexanediol ( equiv), and Cs 2CO 3 ( mmol) was taken in dry DMF (2.0 ml). The mixture was degassed under reduced pressure at rt and refilled with argon (3-4 times). The reaction mixture was then placed on a pre-heated oil bath (130 o C) and heated under argon for 10 h. At this point TLC (silica gel, EtOAc/hexane = 1:3 indicated the absence of starting material 22. The mixture was cooled to rt and diluted with EtOAc (10 ml) and water. The aqueous layer was separated and extracted with EtOAc (2 x 10 ml). The combined organic layer was washed with water (2 x 50 ml) and brine (3 x 50 ml) and dried over Na 2SO 4. The solvent was removed under reduced pressure and residue was purified by chromatography on neutral alumina (EtOAc/hexane = 1:3) to provide the cross-coupling products 23 (22-53%) and 23' (5-17%). Compound 22, 23 and 23' gave colorless crystals from DCM, EtOAc and CHCl 3 respectively and was used for X-ray analysis (for X-ray data, see p. S28). Condition 2: In a sealed tube with a magnetic stir bar, a mixture of vinyl iodide 16/18/20/22 (1.0 mmol), CuI or catalyst ( equiv), cis-1,2- cyclohexanediol ( equiv), and Cs 2CO 3 (0-4.0 equiv) and TEMPO ( equiv) was taken in dry DMF (2.0 ml). The mixture was degassed under reduced pressure at rt and refilled with argon (3-4 times). The reaction mixture was then placed on a pre-heated oil bath (130 o C) and heated under argon for 10 h. At this point TLC (silica gel, EtOAc/hexane = 1:3 indicated the absence of starting material 16/18/20/22. The mixture was cooled to rt and diluted with EtOAc (10 ml) and water. The aqueous layer was separated and extracted with EtOAc (2 x 10 ml). The combined organic layer was washed with water (2 x 50 ml) and brine (3 x 50 ml) and dried over Na 2SO 4. The solvent was removed under reduced pressure and residue was purified by chromatography on neutral alumina (EtOAc/hexane = 1:3) to provide the cross-coupling products 17 (83%) /19 (86%) /21 (82%) /23 (24-89%). Compound 19 gave colorless crystals from EtOAc and was used for X-ray analysis (for X-ray data, see p. S46). S4

5 Cross-coupling of 22 under condition: 1 ( 1 H NMR δ ppm ppm Crude Rx ppm ppm ppm Comparison between condition 1 and 2 Crude Rx: without TEMPO (condition 1) ppm Crude Rx: with TEMPO (condition 2) ppm S5

6 (6S,8S,11aS)-8-methyl-9-methylene-6,8,9,10,11a,12-hexahydro-6,10-methanoindolo[3,2-b]quinolizin-11(5H)- one (17) 1 H NMR (300 MHz, CDCl 3): δ 7.76 (brs, 1H), 7.50 (d, 1H, J = 7.5 Hz), (m, 1H), (m, 2H), 5.12 (d, 1H, J = 2.5 Hz), 5.01 (d, 1H, J = 2.5 Hz), (m, 1H), (m, 1H), 3.74 (d, 1H, J = 5.6 Hz), 3.34 (dd, 1H, J = 15.6, 1.2 Hz), (dd, 1H, J = 3.6, 1.9 Hz), 2.93 (dd, 1H, J = 15.6, 6.1 Hz), ( (m, 1H), (m, 1H), 1.50 (d, 3H, J = 6.8 Hz); All other spectroscopic data was identical with the published data for The material was used for the next step without further characterization. (6S,8S,11aS)-5,8-dimethyl-9-methylene-6,8,9,10,11a,12-hexahydro-6,10-methanoindolo[3,2-b]quinolizin- 11(5H)-one (19) 1 H NMR (300 MHz, CDCl 3): δ 7.50 (d, 1H, J = 7.4 Hz), (m, 1H), 7.18 (td, 1H, J = 7.5, 0.9 Hz), (m, 1H), 5.1 (d, 1H, J = 2.5 Hz), 5.01 (d, 1H, J = 2.5 Hz), 4.41 (dd, 1H, J = 9.5, 2.1 Hz), (m, 1H), 3.72 (d, 2.65 (m, 1H), (m, 1H), 1.49 (d, 3H, J = 6.7 Hz). All other spectroscopic data was identical with the published data for The material was used for the next step without further characterization. 1H, J = 5.6 Hz), 3.6 (s, 3H), 3.34 (dd, 1H, J = 15.6, 1.3 Hz), (m, 1H), 2.92 (dd, 1H, J = 15.6, 6.1 Hz), (6S,8S,11aS)-8-methyl-9-methylene-6,8,9,10,11a,12-hexahydro-6,10-methanoindolo[3,2-b]quinolizin-11(5H)- one (21) 1 H NMR (300 MHz, MeOD): δ 7.42 (d, 1H, J = 7.7 Hz), 7.29 (d, 1H, J = 8.0 Hz), (m, 1H), (m, 1H), 5.14 (d, 1H, J = 2.2 Hz), 5.06 (d, 1H, J = 1.6 Hz), (m, 1H), (m, 1H), 3.71 (d, 1H, J = 6.0 Hz), (m, 1H, merged with solvent), (m, 2H), (m, 1H), (m, 1H), 1.66 (d, 3H, J = 7.1 Hz). 13 C NMR (75 MHz, MeOD): δ (C), (C), (C), (C), (C), (CH), (CH), (CH), (CH), 110.1(CH 2), (C), 66.4 (CH), 58.8 (CH), 51.8 (CH), 44.3 (CH), 36.7 (CH 2), 21.9 (CH 2), 19.2 (CH 3); HRMS (ESI) m/z (M + H) + calcd for C 18H 19N 2O, , found S6

7 (6S,8R,11aS)-5,8-dimethyl-9-methylene-6,8,9,10,11a,12-hexahydro-6,10-methanoindolo[3,2-b]quinolizin- 11(5H)-one (23) 1 H NMR (300 MHz, CDCl 3) δ 7.48 (d, 1H, J = 7.7 Hz), (m, 1H), (m, 1H), (m, 1H), 5.10 (d, 1H, J = 1.8 Hz), 4.98 (d, 1H, J = 1.8 Hz), 4.57 (dd, 1H, J = 9.3, 1.9 Hz), (m, 1H), 3.61 (s, 3H) 3.56 (d, 1H, J = 6.1 Hz), (m, 1H), (m, 2H), (m, 1H), 2.11 (dt, 1H, J = 12.6, 3.2 Hz), 1.67 (d, 3H, J = 7.1 Hz); 13 C NMR (75 MHz, CDCl 3) : δ (C), (C), (C), (C), 126,6 (C), (CH), (CH), (CH), (CH2), (CH), (C), 66.9 (CH), 59.1 (CH), 51.7 (CH), 43.2 (CH), 36.5 (CH2), 29.3 (CH3), 22.6 (CH2), 20.7 (CH3); HRMS (ESI) m/z (M + H) + calcd for C 19H 21N 2O, , found (6S,8R,12aS)-5,8-dimethyl-8,11,12a,13-tetrahydro-5H-6,11-methanoazepino [1',2':1,6]pyrido [3,4-b]indol- 12(6H)-one (23') 1 H NMR (300 MHz, CDCl 3): δ 7.46 (d, 1H, J = 7.7 Hz), (m, 1H), 7.17 (t, 1H, J = 7.4 Hz), 7.07 (t, 1H, J = 7.3 Hz), 5.9 (t, 1H, J = 9.6 Hz), 5.71 (dd, 1H, J = 10.2, 3.2 Hz), 4.6 (d, 1H, J = 8.9 Hz), (m, 1H), 3.89 (d, 1H, J = 5.7 Hz), 3.61 (s, 3H), 3.27 (dd, 1H, J = 15.1, 1.3 Hz), 2.99 (dd, 1H, J = 15.1, 6.0 Hz), (m, 2H), 2.33 (dd, 1H, J = 13.0, 7.2 Hz), 1.56 (d, 3H, J = 7.1 Hz). 13 C NMR (75 MHz, CDCl 3): δ (C), (C), (C), (CH), (CH), 126.7(CH), (CH), (CH), (CH), (CH), (C), 64.2 (CH), 62.4 (CH), 45.9 (CH), 44.3 (CH), 43.0 (CH 2), 29.4 (CH 3), 25.2 (CH 2), 18.9 (CH 3). HRMS (ESI) m/z (M + H) + calcd for C 19H 21N 2O, , found S7

8 Macrocarpine E (5) (5.3 mg, mmol) of the aldehyde 39 was dissolved in EtOH (1 ml) and cooled to 0 o C. Then NaBH 4 (0.93mg, mmol) was to the above solution in one portion. The mixture was stirred at 0 o C for 5 h. After 5 h, TLC and LCMS indicated disappearance of the aldehyde. The reaction mixture was diluted with DCM (5 ml) and poured into ice cold water. The organic layer was separated and aq layer was extracted with additional DCM (2 x 5 ml). The combined organic layer was washed with brine and dried over Na 2SO 4. The solvent was removed under reduced pressure and the residue was purified by chromatography on silica gel from a Pasteur pipette (2-4 % MeOH in DCM) to give 5.1 mg (96%) macrocarpine E (5) as a white color waxy solid. R f : 0.4 (10% MeOH in DCM); 1 H NMR (300 MHz, CDCl 3): δ 7.74 (brs, 1H), 7.49 (d, 1H, J = 7.4 Hz), 7.33 (d, 1H, J = 7.4 Hz), (m, 2H), 4.08 (t, 1H, J = 11.7 Hz), (m, 1H), (m, 1H), (m, 2H), (m,1h), 3.25 (dd, 1H, J = 16.6, 6.7 Hz), 2.86 (d, 1H, J = 6.7 Hz), 2.47 (d, 1H, J = 16.6 Hz), 2.47 (m, 1H, merged), 2.33 (s, 3H), 2.16 (dd, 1H, J = 11.3, 5.2 Hz), (m, 1H), (m, 1H), 1.24 (d, 3H, J = 6.6 Hz), 1.06 (brs, 1H); 13 C NMR (75 MHz, CDCl 3): δ135.7 (C), (C), (C), (CH), (CH), (CH), (CH), (C), 71.3, 68.9 (CH 2), 63.3, 55.0 (CH), 54.6 (CH), 43.5 (CH), 41.6 (CH 3), 39.4 (CH), 31.4 (CH 2), 28.9 (CH), 22.5 (CH 2), 18.8 (CH 3); HRMS (ESI) m/z (M + H) + calcd for C 20H 27N 2O 2, , found [α] 25 D (c 0.45, CHCl 3): lit. [α] 25 D (c 0.8, CHCl 3): -12. The spectroscopic data and optical rotation was in excellent agreement with the natural macrocarpine E. 3 S8

9 Macrocarpine D (4) (4.2 mg, mmol) of the aldehyde 40 was dissolved in EtOH (1mL) and cooled to 0 o C. Then NaBH 4 (0.74 mg, 0.02 mmol) was to the above solution in one portion. The mixture was stirred at 0 o C for 5 h. After 5 h TLC and LCMS indicated disappearance of the aldehyde. The reaction mixture was diluted with DCM (5 ml) and poured into ice cold water. The organic layer was separated and aq layer was extracted with additional DCM (2 x 5 ml). The combined organic layer was washed with brine and dried over Na 2SO 4. The solvent was removed under reduced pressure and the residue was purified by chromatography on silica gel from a Pasteur pipette (1-3 % MeOH in DCM) to give 3.9 mg (92%) macrocarpine D (4) as a white color waxy solid. R f : 0.33 (10% MeOD in DCM); 1 H NMR (500 MHz, CDCl 3): δ 7.71 (brs, 1H), 7.49 (d, 1H, J = 7.5 Hz), 7.32 (d, 1H, J = 7.7 Hz), 7.15 (t, 1H, J = 7.1 Hz), 7.14 (t, 1H, J = 7.1 Hz), 4.06 (t, 1H, J = 11.6 Hz), (m, 1H), 3.74 (dd, 1H, J = 11.4, 4.5 Hz), (m, 2H), 3.35 (dd, 1H, J = 10.7, 8.3 Hz), 3.26 (dd, 1H, J = 16.5, 6.8 Hz), 2.91 (d, 1H, J = 6.8 Hz), 2.43 (d, 1H, J = 16.5 Hz), 2.32 (s, 3H), 2.26 (td, 1H, J = 12.8, 4.0 Hz), (m, 1H), (m, 1H), 1.58 (dt, 1H, J = 12.6, 3.8 Hz), (m, 1H), 1.16 (d, 3H, J = 6.1 Hz); 13 C NMR (75 MHz, CDCl 3): δ (C), (C), (C), (CH), (CH), (CH), (CH), (C), 70.5 (CH), 67.7 (CH 2), 61.7 (CH 2), 55.1 (CH), 54.9 (CH), 46.9 (CH), 43.6 (CH), 41.6 (CH 3), 27.1 (CH), 26.1 (CH 2), 22.5 (CH 2), 20.3 (CH 3); HRMS (ESI) m/z (M + H) + calcd for C 20H 27N 2O 2, , found [α] 25 D (c 0.85, CHCl 3): lit. [α] 25 D(c 0.89, CHCl 3): -43. The spectroscopic data and optical rotation was in excellent agreement with the natural macrocarpine D. 4 S9

10 3. BIOGENETIC NUMBERING FOR MACROCARPINE D (4) AND MACROCARPINE E (5) 3,4 S10

11 4. COMPARISON TABLES 1 & 2 FOR NATURAL AND SYNTHETIC MACROCARPINE D (4) Macrocarpine D (4) Specific rotation: Natural 4 25 : [α] D = -43 (c 0.89, CHCl 3) 25 Synthetic: [α] D = (c 0.85, CHCl 3) Table 1. Comparison of the 1 H NMR Spectral Data for Natural and Synthetic macrocarpine D (4) in CDCl 3 H 1 H Natural 4 (400 MHz) 1 H Synthetic (500 MHz) m m d (7) 2.91 d (6.8) 6b 2.46 d (16) 2.43 d (16.5) 6a 3.27 dd (16, 7) 3.26 dd (16.5, 6.8) d (7.5) 7.49 d(7.5) t (7.5) 7.14t (7.1) t (7.5) 7.15 t (7.1 Hz) d (7.5) 7.32 d (7.7) 14b 1.62 dt (13, 4) 1.58 dt (12.6, 3.8) 14a 2.28 td (13, 4) 2.26 td (12.8, 4.0) m m dt (12, 4) m 17b 3.74 dd (12, 5) 3.74 dd (11.4, 4.5) 17a 4.08 t (12) 4.06 t (11.6) d (6) 1.16 d (6.1) m m (19 and 21b merged together) m m 21a 3.34 dd (11, 8) 3.35 dd (10.7, 8.3) 21b 3.50 dd (11, 5) m N a-h 7.89 br s 7.71 br s N 4-Me 2.34 s 2.32 s S11

12 Table 2. Comparison of the 13 C NMR Spectral Data for Natural and Synthetic macrocarpine D (4) in CDCl 3 C# 13 C Natural 4 (100 MHz) 13 C Synthetic (75 MHz) N 4-Me S12

13 5. COMPARISON TABLES 3 & 4 FOR NATURAL AND SYNTHETIC MACROCARPINE E (5) Macrocarpine E (5) Specific rotation: Natural 3 25 : [α] D = -12 (c 0.8, CHCl 3) 25 Synthetic: [α] D = (c 0.45, CHCl 3) Table 3. Comparison of the 1 H NMR Spectral Data for Natural and Synthetic macrocarpine E (5) in CDCl 3 H 1 H Natural 3 (400 MHz) 1 H Synthetic (300 MHz) br t (3) m d (7) 2.86 d (6.7) 6b 2.43 d (17) 2.47 d (16.6) 6a 3.23 dd (17, 7) 3.25 dd (16.6, 6.7) dd (7, 1)) 7.49 d (7.4) td (7, 1)) m td (7, 1) m dd (7, 1) 7.33 d (7.4) 14b 1.44 ddd (13, 5, 3) m 14a 2.43 td (13, 4) Merged with 6b dt (13, 5) m dd (12, 5) 2.16 dd (11.3, 5.2) 17b 3.76 dd (12, 5) m 17a 4.04 t (12) 4.08 t (11.7) d (6.7) 1.24 d (6.6) (6.7, 2.6) m m 1.06 brs 21a 3.64 dd (11, 4) m 21b 3.71 dd (11, 6) m N 1-H 8.14 br s 7.74 br s N 4-Me 2.30 s 2.33 s S13

14 Table 4. Comparison of the 13 C NMR Spectral Data for Natural and Synthetic macrocarpine E (5) in CDCl 3 C# 13 C Natural 3 (100 MHz) 13 C Synthetic (75 MHz) N 4-Me References: (1) Edwankar, R. V.; Edwankar, C. R.; Deschamps, J.; Cook, J. M. Org. Lett. 2011, 13, (2) Edwankar, R. V.; Edwankar, C. R.; Deschamps, J. R.; Cook, J. M. J. Org. Chem. 2014, 79, (3) Tan, S.-J.; Lim, J.-L.; Low, Y.-Y.; Sim, K.-S.; Lim, S.-H.; Kam, T.-S. J. Nat. Prod. 2014, 77, (4) Lim, S.-H.; Low, Y.-Y.; Sinniah, S. K.; Yong, K.-T.; Sim, K.-S.; Kam, T.-S. Phytochemistry 2014, 98, 204. S14

15 Copies of NMR Spectra ppm 1 H NMR spectrum of 17 (300 MHz, CDCl 3) S15

16 ppm 1 H NMR spectrum of 19 (300 MHz, CDCl 3) S16

17 ppm 1 H NMR spectrum of 21 (300 MHz, MeOD) ppm 13 C NMR spectrum of 21 (75 MHz, MeOD) S17

18 ppm 1 H NMR spectrum of 23 (300 MHz, CDCl 3) ppm 13 C NMR spectrum of 23 (75 MHz, CDCl 3) S18

19 ppm 1 H NMR spectrum of 23' (300 MHz, CDCl 3) ppm 13 C NMR spectrum of 23' (75 MHz, CDCl 3) S19

20 ppm DEPT 135 spectrum of 23' COSY of 23' S20

21 HSQC of 23' HMBC of 23' S21

22 ppm 1 H NMR spectrum of macrocarpine D (4) (500 MHz, CDCl 3) ppm 13 C NMR of macrocarpine D (4) (75 MHz, CDCl 3) S22

23 ppm DEPT 135 of macrocarpine D (4) HSQC of macrocarpine D (4) S23

24 HRMS (ESI) of macrocarpine D (4) S24

25 ppm 1 H NMR spectrum of macrocarpine E (5) (300 MHz, CDCl 3) ppm 13 C NMR spectrum of macrocarpine E (5) (75 MHz, CDCl 3) S25

26 ppm ppm COSY of macrocarpine E (5) HSQC of macrocarpine E (5) S26

27 HRMS (ESI) of macrocarpine E (5) S27

28 8. X-ray Structural Analysis Table 5. Crystal data and structure refinement for 22. Empirical formula C 19H 21IN 2O Formula weight Temperature 150(2) K Wavelength Å Crystal system Monoclinic Space group P2 1 Unit cell dimensions a = (10) Å α= 90 b = (12) Å β= (5) c = (18) Å γ = 90 Volume 882.6(2) Å 3 Z 2 Density (calculated) Mg/m 3 Absorption coefficient mm -1 F(000) 420 Crystal size x x mm 3 Theta range for data collection to Index ranges -8<=h<=8, -10<=k<=10, -16<=l<=13 Reflections collected 3852 Independent reflections 2307 [R(int) = ] Completeness to theta = % Absorption correction Semi-empirical from equivalents Max. and min. transmission and Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 2307 / 1 / 211 Goodness-of-fit on F Final R indices [I>2sigma(I)] R1 = , wr2 = R indices (all data) R1 = , wr2 = Absolute structure parameter 0.278(13) Extinction coefficient (12) Largest diff. peak and hole and e.å -3 S28

29 Table 6. Atomic coordinates (x 10 4 ) and equivalent isotropic displacement parameters (Å 2 x 10 3 ) for 22. U(eq) is defined as one third of the trace of the orthogonalized U ij tensor. x y z U(eq) O(1) 1045(8) 6867(8) 7940(6) 33(2) C(1) 808(12) 5584(11) 7903(8) 28(2) C(2) -1111(11) 4867(13) 7708(9) 36(2) C(3) -1344(11) 3575(13) 6979(8) 36(2) C(4) 572(10) 2835(9) 6997(6) 24(2) C(5) 1583(10) 3428(10) 6213(7) 24(2) N(6) 1074(9) 3167(8) 5187(6) 23(2) C(6) -425(12) 2184(10) 4690(8) 34(2) C(7) 2305(11) 3874(10) 4708(9) 24(2) C(8) 2396(12) 3920(10) 3689(8) 28(2) C(9) 3779(14) 4779(14) 3419(9) 38(2) C(10) 5029(13) 5572(12) 4155(9) 36(2) C(11) 4997(12) 5502(12) 5165(8) 30(2) C(12) 3614(10) 4631(10) 5461(8) 25(2) C(13) 3107(10) 4353(10) 6415(8) 24(2) C(14) 3875(10) 4882(11) 7451(7) 27(2) C(15) 2473(12) 4515(11) 8135(9) 25(2) N(16) 1738(9) 3040(9) 8030(6) 26(2) C(17) 3213(14) 1940(12) 8333(8) 34(2) C(18) 4247(13) 2251(15) 9397(8) 41(3) I(18) 2558(1) 2479(2) 10483(1) 54(1) C(19) 6118(14) 2291(18) 9690(10) 51(3) C(20) 2422(17) 371(14) 8244(12) 44(3) Table 7. Bond lengths [Å] and angles [ ] for 22. O(1)-C(1) 1.192(13) C(1)-C(2) 1.518(12) C(1)-C(15) 1.541(12) C(2)-C(3) 1.529(16) C(2)-H(2A) C(2)-H(2B) C(3)-C(4) 1.546(11) C(3)-H(3A) C(3)-H(3B) C(4)-N(16) 1.488(11) C(4)-C(5) 1.506(11) C(4)-H(4A) C(5)-N(6) 1.378(12) C(5)-C(13) 1.380(12) N(6)-C(7) 1.370(13) N(6)-C(6) 1.469(11) C(6)-H(6A) C(6)-H(6B) C(6)-H(6C) C(7)-C(8) 1.390(14) C(7)-C(12) 1.424(13) C(8)-C(9) 1.384(14) C(8)-H(8A) C(9)-C(10) 1.406(17) C(9)-H(9A) C(10)-C(11) 1.367(16) C(10)-H(10A) C(11)-C(12) 1.405(13) C(11)-H(11A) C(12)-C(13) 1.432(14) C(13)-C(14) 1.476(14) C(14)-C(15) 1.545(13) C(14)-H(14A) C(14)-H(14B) C(15)-N(16) 1.455(12) C(15)-H(15A) S29

30 Table 7. (continued) N(16)-C(17) 1.471(12) C(17)-C(18) 1.504(15) C(17)-C(20) 1.548(15) C(17)-H(17A) C(18)-C(19) 1.338(14) C(18)-I(18) 2.105(11) C(19)-H(19A) C(19)-H(19B) C(20)-H(20A) C(20)-H(20B) C(20)-H(20C) O(1)-C(1)-C(2) 123.9(9) O(1)-C(1)-C(15) 121.4(9) C(2)-C(1)-C(15) 114.5(9) C(1)-C(2)-C(3) 115.2(7) C(1)-C(2)-H(2A) C(3)-C(2)-H(2A) C(1)-C(2)-H(2B) C(3)-C(2)-H(2B) H(2A)-C(2)-H(2B) C(2)-C(3)-C(4) 110.5(7) C(2)-C(3)-H(3A) C(4)-C(3)-H(3A) C(2)-C(3)-H(3B) C(4)-C(3)-H(3B) H(3A)-C(3)-H(3B) N(16)-C(4)-C(5) 110.1(7) N(16)-C(4)-C(3) 107.4(7) C(5)-C(4)-C(3) 113.3(8) N(16)-C(4)-H(4A) C(5)-C(4)-H(4A) C(3)-C(4)-H(4A) N(6)-C(5)-C(13) 110.3(8) N(6)-C(5)-C(4) 124.8(7) C(13)-C(5)-C(4) 124.9(8) C(7)-N(6)-C(5) 108.8(7) C(7)-N(6)-C(6) 124.9(8) C(5)-N(6)-C(6) 126.0(8) N(6)-C(6)-H(6A) N(6)-C(6)-H(6B) H(6A)-C(6)-H(6B) N(6)-C(6)-H(6C) H(6A)-C(6)-H(6C) H(6B)-C(6)-H(6C) N(6)-C(7)-C(8) 130.4(8) N(6)-C(7)-C(12) 107.6(9) C(8)-C(7)-C(12) 122.0(9) C(9)-C(8)-C(7) 117.4(9) C(9)-C(8)-H(8A) C(7)-C(8)-H(8A) C(8)-C(9)-C(10) 120.7(11) C(8)-C(9)-H(9A) C(10)-C(9)-H(9A) C(11)-C(10)-C(9) 122.6(10) C(11)-C(10)-H(10A) C(9)-C(10)-H(10A) C(10)-C(11)-C(12) 117.9(9) C(10)-C(11)-H(11A) C(12)-C(11)-H(11A) C(11)-C(12)-C(7) 119.3(10) C(11)-C(12)-C(13) 133.4(9) C(7)-C(12)-C(13) 107.2(8) C(5)-C(13)-C(12) 106.0(8) C(5)-C(13)-C(14) 121.6(9) C(12)-C(13)-C(14) 132.3(8) C(13)-C(14)-C(15) 108.9(7) C(13)-C(14)-H(14A) C(15)-C(14)-H(14A) C(13)-C(14)-H(14B) C(15)-C(14)-H(14B) H(14A)-C(14)-H(14B) N(16)-C(15)-C(1) 108.5(7) N(16)-C(15)-C(14) 114.8(9) C(1)-C(15)-C(14) 109.0(8) N(16)-C(15)-H(15A) C(1)-C(15)-H(15A) C(14)-C(15)-H(15A) C(15)-N(16)-C(17) 112.5(7) C(15)-N(16)-C(4) 109.7(8) C(17)-N(16)-C(4) 114.7(8) N(16)-C(17)-C(18) 109.2(9) N(16)-C(17)-C(20) 112.4(8) C(18)-C(17)-C(20) 110.9(10) N(16)-C(17)-H(17A) C(18)-C(17)-H(17A) C(20)-C(17)-H(17A) C(19)-C(18)-C(17) 124.6(11) C(19)-C(18)-I(18) 119.6(9) C(17)-C(18)-I(18) 115.7(7) C(18)-C(19)-H(19A) C(18)-C(19)-H(19B) H(19A)-C(19)-H(19B) C(17)-C(20)-H(20A) C(17)-C(20)-H(20B) H(20A)-C(20)-H(20B) C(17)-C(20)-H(20C) H(20A)-C(20)-H(20C) H(20B)-C(20)-H(20C) S30

31 Table 8. Anisotropic displacement parameters (Å 2 x 10 3 ) for 22. The anisotropic displacement factor exponent takes the form: -2π 2 [ h 2 a* 2 U h k a* b* U 12 ] U 11 U 22 U 33 U 23 U 13 U 12 O(1) 37(3) 22(3) 40(5) -1(3) 5(2) 2(2) C(1) 38(4) 22(5) 26(5) -4(4) 13(3) 7(3) C(2) 27(3) 41(6) 44(6) -7(5) 16(3) 4(4) C(3) 29(4) 43(5) 40(6) -5(5) 13(3) -6(4) C(4) 32(3) 24(5) 18(4) -1(3) 9(3) -6(3) C(5) 26(3) 24(5) 25(5) 1(4) 13(3) 0(3) N(6) 30(3) 14(3) 27(4) -1(3) 9(3) -1(3) C(6) 46(4) 22(6) 37(5) -7(4) 13(3) -18(4) C(7) 32(4) 15(5) 27(5) -2(4) 10(3) -3(3) C(8) 42(4) 21(5) 22(5) 4(4) 11(3) -1(3) C(9) 51(5) 42(6) 26(6) 8(5) 20(4) -3(4) C(10) 41(4) 34(5) 39(6) 5(5) 19(4) -6(4) C(11) 32(3) 30(4) 29(6) 7(4) 8(3) -7(4) C(12) 24(3) 24(4) 28(5) 1(4) 10(3) 2(3) C(13) 25(3) 23(5) 25(5) 8(4) 8(3) 0(3) C(14) 25(3) 26(5) 30(5) 7(4) 9(3) -6(3) C(15) 33(4) 21(5) 23(5) -2(4) 9(3) -2(4) N(16) 33(3) 15(3) 30(4) -4(3) 8(3) 3(3) C(17) 50(5) 27(5) 26(6) 0(4) 12(4) 5(4) C(18) 48(4) 44(7) 31(5) 7(6) 13(4) 7(5) I(18) 81(1) 54(1) 32(1) 8(1) 22(1) -5(1) C(19) 46(4) 51(8) 51(7) 9(7) -2(4) 5(5) C(20) 52(6) 28(6) 51(8) -1(6) 7(5) -7(5) S31

32 Table 9. Hydrogen coordinates (x 10 4 ) and isotropic displacement parameters (Å 2 x 10 3 ) for 22. x y z U(eq) H(2A) H(2B) H(3A) H(3B) H(4A) H(6A) H(6B) H(6C) H(8A) H(9A) H(10A) H(11A) H(14A) H(14B) H(15A) H(17A) H(19A) H(19B) H(20A) H(20B) H(20C) S32

33 Table 10. Torsion angles [ ] for 22. O(1)-C(1)-C(2)-C(3) 137.6(12) C(15)-C(1)-C(2)-C(3) -46.9(13) C(1)-C(2)-C(3)-C(4) 27.0(13) C(2)-C(3)-C(4)-N(16) 30.2(11) C(2)-C(3)-C(4)-C(5) -91.7(10) N(16)-C(4)-C(5)-N(6) 166.8(8) C(3)-C(4)-C(5)-N(6) -72.8(11) N(16)-C(4)-C(5)-C(13) -15.7(11) C(3)-C(4)-C(5)-C(13) 104.6(10) C(13)-C(5)-N(6)-C(7) 2.3(10) C(4)-C(5)-N(6)-C(7) (8) C(13)-C(5)-N(6)-C(6) 177.0(8) C(4)-C(5)-N(6)-C(6) -5.3(14) C(5)-N(6)-C(7)-C(8) 178.7(9) C(6)-N(6)-C(7)-C(8) 3.9(15) C(5)-N(6)-C(7)-C(12) -1.1(10) C(6)-N(6)-C(7)-C(12) (8) N(6)-C(7)-C(8)-C(9) 177.8(10) C(12)-C(7)-C(8)-C(9) -2.4(14) C(7)-C(8)-C(9)-C(10) -0.1(16) C(8)-C(9)-C(10)-C(11) 2.3(17) C(9)-C(10)-C(11)-C(12) -1.9(16) C(10)-C(11)-C(12)-C(7) -0.5(15) C(10)-C(11)-C(12)-C(13) (10) N(6)-C(7)-C(12)-C(11) (9) C(8)-C(7)-C(12)-C(11) 2.7(14) N(6)-C(7)-C(12)-C(13) -0.3(10) C(8)-C(7)-C(12)-C(13) 179.8(8) N(6)-C(5)-C(13)-C(12) -2.4(10) C(4)-C(5)-C(13)-C(12) 179.8(8) N(6)-C(5)-C(13)-C(14) 176.4(8) C(4)-C(5)-C(13)-C(14) -1.4(13) C(11)-C(12)-C(13)-C(5) 178.2(10) C(7)-C(12)-C(13)-C(5) 1.7(9) C(11)-C(12)-C(13)-C(14) -0.4(18) C(7)-C(12)-C(13)-C(14) (9) C(5)-C(13)-C(14)-C(15) -12.2(12) C(12)-C(13)-C(14)-C(15) 166.3(9) O(1)-C(1)-C(15)-N(16) 179.9(11) C(2)-C(1)-C(15)-N(16) 4.2(13) O(1)-C(1)-C(15)-C(14) -54.4(13) C(2)-C(1)-C(15)-C(14) 129.9(9) C(13)-C(14)-C(15)-N(16) 46.0(10) C(13)-C(14)-C(15)-C(1) -75.9(10) C(1)-C(15)-N(16)-C(17) (9) C(14)-C(15)-N(16)-C(17) 63.3(11) C(1)-C(15)-N(16)-C(4) 56.6(10) C(14)-C(15)-N(16)-C(4) -65.6(9) C(5)-C(4)-N(16)-C(15) 46.6(9) C(3)-C(4)-N(16)-C(15) -77.2(9) C(5)-C(4)-N(16)-C(17) -81.1(10) C(3)-C(4)-N(16)-C(17) 155.1(8) C(15)-N(16)-C(17)-C(18) 55.2(11) C(4)-N(16)-C(17)-C(18) (8) C(15)-N(16)-C(17)-C(20) 178.7(9) C(4)-N(16)-C(17)-C(20) -55.0(12) N(16)-C(17)-C(18)-C(19) (14) C(20)-C(17)-C(18)-C(19) 104.0(15) N(16)-C(17)-C(18)-I(18) 52.9(11) C(20)-C(17)-C(18)-I(18) -71.5(11) S33

34 Table 11. Crystal data and structure refinement for 23. Empirical formula C 19H 20N 2O Formula weight Temperature 150(2) K Wavelength Å Crystal system Orthorhombic Space group P Unit cell dimensions a = (5) Å α= 90 b = (6) Å β= 90 c = (7) Å γ = 90 Volume (15) Å 3 Z 4 Density (calculated) Mg/m 3 Absorption coefficient mm -1 F(000) 624 Crystal size x x mm 3 Theta range for data collection to Index ranges -9<=h<=9, -15<=k<=15, -26<=l<=26 Reflections collected Independent reflections 4097 [R(int) = ] Completeness to theta = % Absorption correction None Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 4097 / 0 / 201 Goodness-of-fit on F Final R indices [I>2sigma(I)] R1 = , wr2 = R indices (all data) R1 = , wr2 = Absolute structure parameter -0.8(5) Extinction coefficient n/a Largest diff. peak and hole and e.å -3 S34

35 Table 12. Atomic coordinates (x 10 4 ) and equivalent isotropic displacement parameters (Å 2 x 10 3 ) for 23. U(eq) is defined as one third of the trace of the orthogonalized U ij tensor. x y z U(eq) N(1) 5237(2) 2088(1) 2412(1) 19(1) C(2) 5643(3) 1860(2) 1666(1) 24(1) C(2A) 7805(3) 1597(2) 1542(1) 33(1) C(3) 4866(3) 2851(2) 1227(1) 25(1) C(3A) 4704(3) 2840(2) 544(1) 39(1) C(4) 4259(2) 3859(2) 1672(1) 21(1) C(5) 6001(3) 4157(2) 2153(1) 20(1) C(6) 6327(2) 3124(2) 2654(1) 18(1) C(7) 5611(2) 3390(2) 3370(1) 18(1) N(8) 6589(2) 4089(1) 3838(1) 19(1) C(8) 8499(2) 4618(2) 3752(1) 24(1) C(9) 5491(2) 4141(2) 4440(1) 20(1) C(10) 5887(3) 4693(2) 5066(1) 25(1) C(11) 4548(3) 4549(2) 5597(1) 29(1) C(12) 2868(3) 3868(2) 5514(1) 28(1) C(13) 2451(3) 3337(2) 4889(1) 24(1) C(14) 3777(3) 3468(2) 4339(1) 19(1) C(15) 3884(2) 3017(2) 3649(1) 18(1) C(16) 2504(3) 2274(2) 3251(1) 21(1) C(17) 3108(2) 2308(2) 2489(1) 19(1) O(18) 1048(2) 3941(1) 2209(1) 30(1) C(18) 2597(3) 3445(2) 2135(1) 20(1) Table 13. Bond lengths [Å] and angles [ ] for 23. N(1)-C(17) 1.484(2) N(1)-C(2) 1.489(2) N(1)-C(6) 1.493(2) C(2)-C(3) 1.527(3) C(2)-C(2A) 1.528(3) C(2)-H(2A) C(2A)-H(2AA) C(2A)-H(2AB) C(2A)-H(2AC) C(3)-C(3A) 1.321(3) C(3)-C(4) 1.513(3) C(3A)-H(3AA) C(3A)-H(3AB) C(4)-C(18) 1.524(2) C(4)-C(5) 1.548(2) C(4)-H(4A) C(5)-C(6) 1.560(2) C(5)-H(5A) C(5)-H(5B) C(6)-C(7) 1.497(2) C(6)-H(6A) C(7)-C(15) 1.368(2) C(7)-N(8) 1.387(2) N(8)-C(9) 1.385(2) N(8)-C(8) 1.453(2) C(8)-H(8A) C(8)-H(8B) C(8)-H(8C) C(9)-C(10) 1.395(3) C(9)-C(14) 1.424(2) C(10)-C(11) 1.384(3) C(10)-H(10A) C(11)-C(12) 1.405(3) C(11)-H(11A) C(12)-C(13) 1.385(3) C(12)-H(12A) S35

36 Table 13. (continued) C(13)-C(14) 1.404(3) C(13)-H(13A) C(14)-C(15) 1.433(2) C(15)-C(16) 1.493(2) C(16)-C(17) 1.527(2) C(16)-H(16A) C(16)-H(16B) C(17)-C(18) 1.530(3) C(17)-H(17A) O(18)-C(18) 1.214(2) C(17)-N(1)-C(2) (14) C(17)-N(1)-C(6) (13) C(2)-N(1)-C(6) (14) N(1)-C(2)-C(3) (15) N(1)-C(2)-C(2A) (16) C(3)-C(2)-C(2A) (17) N(1)-C(2)-H(2A) C(3)-C(2)-H(2A) C(2A)-C(2)-H(2A) C(2)-C(2A)-H(2AA) C(2)-C(2A)-H(2AB) H(2AA)-C(2A)-H(2AB) C(2)-C(2A)-H(2AC) H(2AA)-C(2A)-H(2AC) H(2AB)-C(2A)-H(2AC) C(3A)-C(3)-C(4) (19) C(3A)-C(3)-C(2) (19) C(4)-C(3)-C(2) (16) C(3)-C(3A)-H(3AA) C(3)-C(3A)-H(3AB) H(3AA)-C(3A)-H(3AB) C(3)-C(4)-C(18) (15) C(3)-C(4)-C(5) (15) C(18)-C(4)-C(5) (14) C(3)-C(4)-H(4A) C(18)-C(4)-H(4A) C(5)-C(4)-H(4A) C(4)-C(5)-C(6) (14) C(4)-C(5)-H(5A) C(6)-C(5)-H(5A) C(4)-C(5)-H(5B) C(6)-C(5)-H(5B) H(5A)-C(5)-H(5B) N(1)-C(6)-C(7) (14) N(1)-C(6)-C(5) (14) C(7)-C(6)-C(5) (14) N(1)-C(6)-H(6A) C(7)-C(6)-H(6A) C(5)-C(6)-H(6A) C(15)-C(7)-N(8) (15) C(15)-C(7)-C(6) (16) N(8)-C(7)-C(6) (15) C(9)-N(8)-C(7) (14) C(9)-N(8)-C(8) (15) C(7)-N(8)-C(8) (15) N(8)-C(8)-H(8A) N(8)-C(8)-H(8B) H(8A)-C(8)-H(8B) N(8)-C(8)-H(8C) H(8A)-C(8)-H(8C) H(8B)-C(8)-H(8C) N(8)-C(9)-C(10) (17) N(8)-C(9)-C(14) (15) C(10)-C(9)-C(14) (16) C(11)-C(10)-C(9) (18) C(11)-C(10)-H(10A) C(9)-C(10)-H(10A) C(10)-C(11)-C(12) (19) C(10)-C(11)-H(11A) C(12)-C(11)-H(11A) C(13)-C(12)-C(11) (18) C(13)-C(12)-H(12A) C(11)-C(12)-H(12A) C(12)-C(13)-C(14) (18) C(12)-C(13)-H(13A) C(14)-C(13)-H(13A) C(13)-C(14)-C(9) (17) C(13)-C(14)-C(15) (17) C(9)-C(14)-C(15) (15) C(7)-C(15)-C(14) (16) C(7)-C(15)-C(16) (15) C(14)-C(15)-C(16) (16) C(15)-C(16)-C(17) (14) C(15)-C(16)-H(16A) C(17)-C(16)-H(16A) C(15)-C(16)-H(16B) C(17)-C(16)-H(16B) H(16A)-C(16)-H(16B) N(1)-C(17)-C(16) (15) N(1)-C(17)-C(18) (14) C(16)-C(17)-C(18) (15) N(1)-C(17)-H(17A) C(16)-C(17)-H(17A) C(18)-C(17)-H(17A) O(18)-C(18)-C(4) (17) O(18)-C(18)-C(17) (17) C(4)-C(18)-C(17) (15) S36

37 Table 14. Anisotropic displacement parameters (Å 2 x 10 3 ) for 23. The anisotropic displacement factor exponent takes the form: -2π 2 [ h 2 a* 2 U h k a* b* U 12 ] U 11 U 22 U 33 U 23 U 13 U 12 N(1) 16(1) 16(1) 25(1) -1(1) 4(1) 0(1) C(2) 22(1) 22(1) 27(1) -6(1) 4(1) 0(1) C(2A) 26(1) 36(1) 37(1) -5(1) 9(1) 8(1) C(3) 19(1) 30(1) 26(1) -2(1) 2(1) -2(1) C(3A) 47(1) 43(1) 28(1) -5(1) 1(1) 0(1) C(4) 18(1) 22(1) 23(1) 3(1) 0(1) 1(1) C(5) 19(1) 18(1) 23(1) 0(1) 3(1) -2(1) C(6) 13(1) 17(1) 24(1) 1(1) 1(1) 1(1) C(7) 15(1) 16(1) 22(1) 2(1) -1(1) 1(1) N(8) 17(1) 22(1) 20(1) 1(1) -1(1) -2(1) C(8) 15(1) 27(1) 31(1) 1(1) -2(1) -3(1) C(9) 20(1) 19(1) 22(1) 5(1) -1(1) 3(1) C(10) 27(1) 22(1) 26(1) 0(1) -5(1) 1(1) C(11) 38(1) 27(1) 22(1) -1(1) -2(1) 7(1) C(12) 35(1) 26(1) 22(1) 3(1) 8(1) 6(1) C(13) 24(1) 21(1) 25(1) 5(1) 4(1) 2(1) C(14) 20(1) 16(1) 20(1) 5(1) 0(1) 2(1) C(15) 17(1) 16(1) 21(1) 2(1) 1(1) 1(1) C(16) 18(1) 19(1) 25(1) -1(1) 4(1) -4(1) C(17) 15(1) 19(1) 24(1) -3(1) 1(1) -3(1) O(18) 18(1) 37(1) 33(1) 3(1) 1(1) 7(1) C(18) 16(1) 24(1) 21(1) -3(1) -2(1) -1(1) S37

38 Table 15. Hydrogen coordinates (x 10 4 ) and isotropic displacement parameters (Å 2 x 10 3 ) for 23. x y z U(eq) H(2A) H(2AA) H(2AB) H(2AC) H(3AA) H(3AB) H(4A) H(5A) H(5B) H(6A) H(8A) H(8B) H(8C) H(10A) H(11A) H(12A) H(13A) H(16A) H(16B) H(17A) S38

39 Table 16. Torsion angles [ ] for 23. C(17)-N(1)-C(2)-C(3) 54.52(19) C(6)-N(1)-C(2)-C(3) (18) C(17)-N(1)-C(2)-C(2A) (16) C(6)-N(1)-C(2)-C(2A) 62.6(2) N(1)-C(2)-C(3)-C(3A) (18) C(2A)-C(2)-C(3)-C(3A) 65.7(3) N(1)-C(2)-C(3)-C(4) 10.4(2) C(2A)-C(2)-C(3)-C(4) (18) C(3A)-C(3)-C(4)-C(18) 116.7(2) C(2)-C(3)-C(4)-C(18) (18) C(3A)-C(3)-C(4)-C(5) (2) C(2)-C(3)-C(4)-C(5) 52.36(19) C(3)-C(4)-C(5)-C(6) (18) C(18)-C(4)-C(5)-C(6) 49.43(18) C(17)-N(1)-C(6)-C(7) 53.33(17) C(2)-N(1)-C(6)-C(7) (13) C(17)-N(1)-C(6)-C(5) (18) C(2)-N(1)-C(6)-C(5) 49.95(18) C(4)-C(5)-C(6)-N(1) 13.80(19) C(4)-C(5)-C(6)-C(7) (16) N(1)-C(6)-C(7)-C(15) -19.8(2) C(5)-C(6)-C(7)-C(15) 101.8(2) N(1)-C(6)-C(7)-N(8) (15) C(5)-C(6)-C(7)-N(8) -75.9(2) C(15)-C(7)-N(8)-C(9) 1.7(2) C(6)-C(7)-N(8)-C(9) (15) C(15)-C(7)-N(8)-C(8) (16) C(6)-C(7)-N(8)-C(8) -4.7(3) C(7)-N(8)-C(9)-C(10) (18) C(8)-N(8)-C(9)-C(10) 1.5(3) C(7)-N(8)-C(9)-C(14) -0.75(19) C(8)-N(8)-C(9)-C(14) (15) N(8)-C(9)-C(10)-C(11) (18) C(14)-C(9)-C(10)-C(11) 0.9(3) C(9)-C(10)-C(11)-C(12) 0.5(3) C(10)-C(11)-C(12)-C(13) -1.8(3) C(11)-C(12)-C(13)-C(14) 1.6(3) C(12)-C(13)-C(14)-C(9) -0.2(3) C(12)-C(13)-C(14)-C(15) (19) N(8)-C(9)-C(14)-C(13) (16) C(10)-C(9)-C(14)-C(13) -1.1(3) N(8)-C(9)-C(14)-C(15) -0.39(19) C(10)-C(9)-C(14)-C(15) (16) N(8)-C(7)-C(15)-C(14) -1.90(19) C(6)-C(7)-C(15)-C(14) (15) N(8)-C(7)-C(15)-C(16) (16) C(6)-C(7)-C(15)-C(16) 0.3(3) C(13)-C(14)-C(15)-C(7) (19) C(9)-C(14)-C(15)-C(7) 1.39(19) C(13)-C(14)-C(15)-C(16) 4.1(3) C(9)-C(14)-C(15)-C(16) (18) C(7)-C(15)-C(16)-C(17) -14.3(2) C(14)-C(15)-C(16)-C(17) (18) C(2)-N(1)-C(17)-C(16) (14) C(6)-N(1)-C(17)-C(16) (18) C(2)-N(1)-C(17)-C(18) (18) C(6)-N(1)-C(17)-C(18) 52.10(18) C(15)-C(16)-C(17)-N(1) 49.4(2) C(15)-C(16)-C(17)-C(18) (18) C(3)-C(4)-C(18)-O(18) (19) C(5)-C(4)-C(18)-O(18) 114.5(2) C(3)-C(4)-C(18)-C(17) 48.73(19) C(5)-C(4)-C(18)-C(17) (18) N(1)-C(17)-C(18)-O(18) (17) C(16)-C(17)-C(18)-O(18) -43.5(2) N(1)-C(17)-C(18)-C(4) 13.6(2) C(16)-C(17)-C(18)-C(4) (15) S39

40 Table 17. Crystal data and structure refinement for 23'. Empirical formula C 57H 60N 6O 5.04 Formula weight Temperature 150(2) K Wavelength Å Crystal system Trigonal Space group R3 Unit cell dimensions a = (13) Å α= 90 b = (13) Å β= 90 c = (5) Å γ = 120 Volume (5) Å 3 Z 3 Density (calculated) Mg/m 3 Absorption coefficient mm -1 F(000) 1453 Crystal size x x mm 3 Theta range for data collection to Index ranges -33<=h<=24, -33<=k<=30, -9<=l<=5 Reflections collected 6956 Independent reflections 3408 [R(int) = ] Completeness to theta = % Absorption correction None Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 3408 / 1 / 212 Goodness-of-fit on F Final R indices [I>2sigma(I)] R1 = , wr2 = R indices (all data) R1 = , wr2 = Absolute structure parameter 1.4(10) Extinction coefficient 0.005(3) Largest diff. peak and hole and e.å -3 S40

41 Table 18. Atomic coordinates (x 10 4 ) and equivalent isotropic displacement parameters (Å 2 x 10 3 ) for 23'. U(eq) is defined as one third of the trace of the orthogonalized U ij tensor. x y z U(eq) N(1) 4694(3) 8469(3) 3446(9) 35(1) C(2) 4445(3) 8858(4) 2661(11) 37(2) C(2A) 4296(6) 8736(6) 592(14) 63(3) C(3) 4824(4) 9566(4) 2991(11) 42(2) C(4) 5404(4) 9865(4) 3726(11) 40(2) C(5) 5776(3) 9550(3) 4354(11) 38(2) C(6) 5867(3) 9196(3) 2754(11) 36(2) C(7) 5262(3) 8518(3) 2527(10) 30(1) C(8) 5368(3) 8024(3) 3400(10) 31(1) N(9) 5726(3) 7790(3) 2598(9) 32(1) C(9) 6069(4) 7996(4) 895(13) 47(2) C(10) 5723(3) 7357(3) 3800(10) 32(1) C(11) 6013(3) 6987(3) 3627(12) 40(2) C(12) 5940(3) 6583(3) 5051(14) 43(2) C(13) 5568(4) 6528(4) 6602(12) 42(2) C(14) 5277(4) 6892(3) 6782(11) 38(2) C(15) 5355(3) 7306(3) 5354(11) 36(2) C(16) 5136(3) 7752(3) 5059(10) 35(2) C(17) 4731(4) 7922(4) 6197(12) 41(2) C(18) 4788(3) 8535(3) 5443(11) 35(2) C(19) 5424(3) 9120(3) 5971(10) 33(1) O(19) 5610(3) 9232(3) 7558(8) 54(2) O(1S) 2982(8) 7106(8) 400(20) 52(6) O(2S) 3636(7) 7264(7) 2620(20) 23(6) S41

42 Table 19. Bond lengths [Å] and angles [ ] for 23'. N(1)-C(18) 1.455(10) N(1)-C(2) 1.470(9) N(1)-C(7) 1.484(8) C(2)-C(3) 1.513(11) C(2)-C(2A) 1.530(12) C(2)-H(2A) C(2A)-H(2AA) C(2A)-H(2AB) C(2A)-H(2AC) C(3)-C(4) 1.335(12) C(3)-H(3A) C(4)-C(5) 1.518(10) C(4)-H(4A) C(5)-C(19) 1.516(11) C(5)-C(6) 1.523(11) C(5)-H(5A) C(6)-C(7) 1.578(10) C(6)-H(6A) C(6)-H(6B) C(7)-C(8) 1.491(9) C(7)-H(7A) C(8)-C(16) 1.348(10) C(8)-N(9) 1.386(8) N(9)-C(10) 1.363(9) N(9)-C(9) 1.428(10) C(9)-H(9A) C(9)-H(9B) C(9)-H(9C) C(10)-C(11) 1.400(10) C(10)-C(15) 1.403(10) C(11)-C(12) 1.372(13) C(11)-H(11A) C(12)-C(13) 1.404(13) C(12)-H(12A) C(13)-C(14) 1.390(11) C(13)-H(13A) C(14)-C(15) 1.388(11) C(14)-H(14A) C(15)-C(16) 1.443(10) C(16)-C(17) 1.493(10) C(17)-C(18) 1.530(10) C(17)-H(17A) C(17)-H(17B) C(18)-C(19) 1.539(10) C(18)-H(18A) C(19)-O(19) 1.212(9) C(18)-N(1)-C(2) 113.7(5) C(18)-N(1)-C(7) 110.2(5) C(2)-N(1)-C(7) 116.4(6) N(1)-C(2)-C(3) 117.5(6) N(1)-C(2)-C(2A) 112.6(6) C(3)-C(2)-C(2A) 109.0(7) N(1)-C(2)-H(2A) C(3)-C(2)-H(2A) C(2A)-C(2)-H(2A) C(2)-C(2A)-H(2AA) C(2)-C(2A)-H(2AB) H(2AA)-C(2A)-H(2AB) C(2)-C(2A)-H(2AC) H(2AA)-C(2A)-H(2AC) H(2AB)-C(2A)-H(2AC) C(4)-C(3)-C(2) 124.1(7) C(4)-C(3)-H(3A) C(2)-C(3)-H(3A) C(3)-C(4)-C(5) 125.4(7) C(3)-C(4)-H(4A) C(5)-C(4)-H(4A) C(19)-C(5)-C(4) 107.7(6) C(19)-C(5)-C(6) 112.6(6) C(4)-C(5)-C(6) 110.6(6) C(19)-C(5)-H(5A) C(4)-C(5)-H(5A) C(6)-C(5)-H(5A) C(5)-C(6)-C(7) 110.3(5) C(5)-C(6)-H(6A) C(7)-C(6)-H(6A) C(5)-C(6)-H(6B) C(7)-C(6)-H(6B) H(6A)-C(6)-H(6B) N(1)-C(7)-C(8) 106.1(5) N(1)-C(7)-C(6) 112.6(5) C(8)-C(7)-C(6) 110.7(5) N(1)-C(7)-H(7A) C(8)-C(7)-H(7A) C(6)-C(7)-H(7A) C(16)-C(8)-N(9) 111.3(6) C(16)-C(8)-C(7) 125.0(6) N(9)-C(8)-C(7) 123.7(6) C(10)-N(9)-C(8) 107.0(6) C(10)-N(9)-C(9) 126.6(6) C(8)-N(9)-C(9) 126.3(6) N(9)-C(9)-H(9A) N(9)-C(9)-H(9B) H(9A)-C(9)-H(9B) N(9)-C(9)-H(9C) H(9A)-C(9)-H(9C) H(9B)-C(9)-H(9C) N(9)-C(10)-C(11) 129.2(7) C(11)-C(12)-H(12A) C(13)-C(12)-H(12A) S42

43 Table 19. (continued) N(9)-C(10)-C(15) 109.4(6) C(11)-C(10)-C(15) 121.5(7) C(12)-C(11)-C(10) 117.9(7) C(12)-C(11)-H(11A) C(10)-C(11)-H(11A) C(11)-C(12)-C(13) 120.7(7) C(14)-C(13)-C(12) 121.7(7) C(14)-C(13)-H(13A) C(12)-C(13)-H(13A) C(15)-C(14)-C(13) 117.8(7) C(15)-C(14)-H(14A) C(13)-C(14)-H(14A) C(14)-C(15)-C(10) 120.4(7) C(14)-C(15)-C(16) 133.5(7) C(10)-C(15)-C(16) 106.1(6) C(8)-C(16)-C(15) 106.2(6) C(8)-C(16)-C(17) 121.6(6) C(15)-C(16)-C(17) 132.2(6) C(16)-C(17)-C(18) 109.1(6) C(16)-C(17)-H(17A) C(18)-C(17)-H(17A) C(16)-C(17)-H(17B) C(18)-C(17)-H(17B) H(17A)-C(17)-H(17B) N(1)-C(18)-C(17) 108.1(6) N(1)-C(18)-C(19) 112.1(6) C(17)-C(18)-C(19) 111.9(6) N(1)-C(18)-H(18A) C(17)-C(18)-H(18A) C(19)-C(18)-H(18A) O(19)-C(19)-C(5) 123.6(7) O(19)-C(19)-C(18) 122.2(7) C(5)-C(19)-C(18) 114.1(6) Table 20. Anisotropic displacement parameters (Å 2 x 10 3 ) for 23'. The anisotropic displacement factor exponent takes the form: -2π 2 [ h 2 a* 2 U h k a* b* U 12 ] U 11 U 22 U 33 U 23 U 13 U 12 N(1) 28(3) 37(3) 45(4) 0(2) 5(2) 20(2) C(2) 34(3) 45(4) 40(4) -9(3) -12(3) 25(3) C(2A) 80(7) 76(7) 56(6) -17(5) -32(5) 57(6) C(3) 48(4) 46(4) 43(4) 12(3) 10(3) 31(4) C(4) 47(4) 34(3) 42(4) -2(3) 4(3) 23(3) C(5) 30(3) 33(3) 48(4) -7(3) -4(3) 14(3) C(6) 34(3) 35(3) 40(4) 5(3) 7(3) 18(3) C(7) 28(3) 30(3) 33(3) -1(3) 3(3) 15(2) C(8) 31(3) 29(3) 34(3) -2(3) 7(3) 17(3) N(9) 30(3) 28(2) 40(3) 1(2) 5(2) 14(2) C(9) 52(4) 44(4) 51(5) 7(4) 21(4) 28(4) C(10) 20(2) 28(3) 38(4) -1(3) 4(2) 6(2) C(11) 23(3) 30(3) 57(5) -8(3) 5(3) 5(2) C(12) 26(3) 29(3) 75(6) -7(3) -3(3) 15(3) C(13) 42(4) 38(4) 47(4) 4(3) -2(3) 22(3) C(14) 37(3) 31(3) 40(4) 2(3) 2(3) 13(3) C(15) 21(3) 34(3) 48(4) 4(3) 6(3) 11(2) C(16) 29(3) 34(3) 41(4) 11(3) 7(3) 16(3) C(17) 40(4) 37(4) 48(4) 14(3) 19(3) 20(3) C(18) 33(3) 41(3) 39(4) 2(3) 3(3) 25(3) C(19) 37(3) 40(3) 35(3) -6(3) -3(3) 29(3) O(19) 60(4) 71(4) 42(3) -6(3) -6(3) 41(3) S43

44 Table 21. Hydrogen coordinates (x 10 4 ) and isotropic displacement parameters (Å 2 x 10 3 ) for 23'. x y z U(eq) H(2A) H(2AA) H(2AB) H(2AC) H(3A) H(4A) H(5A) H(6A) H(6B) H(7A) H(9A) H(9B) H(9C) H(11A) H(12A) H(13A) H(14A) H(17A) H(17B) H(18A) S44

45 Table 22. Torsion angles [ ] for 23'. C(18)-N(1)-C(2)-C(3) 57.2(9) C(7)-N(1)-C(2)-C(3) -72.5(8) C(18)-N(1)-C(2)-C(2A) (8) C(7)-N(1)-C(2)-C(2A) 55.4(9) N(1)-C(2)-C(3)-C(4) 9.3(12) C(2A)-C(2)-C(3)-C(4) (9) C(2)-C(3)-C(4)-C(5) -0.3(13) C(3)-C(4)-C(5)-C(19) -65.1(10) C(3)-C(4)-C(5)-C(6) 58.3(10) C(19)-C(5)-C(6)-C(7) 37.6(8) C(4)-C(5)-C(6)-C(7) -83.1(7) C(18)-N(1)-C(7)-C(8) 55.9(7) C(2)-N(1)-C(7)-C(8) (6) C(18)-N(1)-C(7)-C(6) -65.2(7) C(2)-N(1)-C(7)-C(6) 66.2(8) C(5)-C(6)-C(7)-N(1) 18.8(8) C(5)-C(6)-C(7)-C(8) -99.7(7) N(1)-C(7)-C(8)-C(16) -20.0(9) C(6)-C(7)-C(8)-C(16) 102.3(8) N(1)-C(7)-C(8)-N(9) 160.4(6) C(6)-C(7)-C(8)-N(9) -77.2(8) C(16)-C(8)-N(9)-C(10) -0.4(8) C(7)-C(8)-N(9)-C(10) 179.2(6) C(16)-C(8)-N(9)-C(9) (7) C(7)-C(8)-N(9)-C(9) 3.1(11) C(8)-N(9)-C(10)-C(11) 179.7(7) C(9)-N(9)-C(10)-C(11) -4.3(12) C(8)-N(9)-C(10)-C(15) 1.0(7) C(9)-N(9)-C(10)-C(15) 177.0(7) N(9)-C(10)-C(11)-C(12) 179.8(7) C(15)-C(10)-C(11)-C(12) -1.7(10) C(10)-C(11)-C(12)-C(13) 2.1(10) C(11)-C(12)-C(13)-C(14) -1.9(12) C(12)-C(13)-C(14)-C(15) 1.2(11) C(13)-C(14)-C(15)-C(10) -0.7(11) C(13)-C(14)-C(15)-C(16) (7) N(9)-C(10)-C(15)-C(14) 179.8(7) C(11)-C(10)-C(15)-C(14) 1.0(10) N(9)-C(10)-C(15)-C(16) -1.2(8) C(11)-C(10)-C(15)-C(16) 180.0(6) N(9)-C(8)-C(16)-C(15) -0.3(8) C(7)-C(8)-C(16)-C(15) (6) N(9)-C(8)-C(16)-C(17) (7) C(7)-C(8)-C(16)-C(17) 0.8(12) C(14)-C(15)-C(16)-C(8) 179.7(8) C(10)-C(15)-C(16)-C(8) 0.9(8) C(14)-C(15)-C(16)-C(17) -1.1(15) C(10)-C(15)-C(16)-C(17) (8) C(8)-C(16)-C(17)-C(18) -14.7(10) C(15)-C(16)-C(17)-C(18) 166.1(7) C(2)-N(1)-C(18)-C(17) 153.2(6) C(7)-N(1)-C(18)-C(17) -74.1(7) C(2)-N(1)-C(18)-C(19) -83.0(7) C(7)-N(1)-C(18)-C(19) 49.7(7) C(16)-C(17)-C(18)-N(1) 49.0(8) C(16)-C(17)-C(18)-C(19) -74.9(8) C(4)-C(5)-C(19)-O(19) (7) C(6)-C(5)-C(19)-O(19) 129.3(7) C(4)-C(5)-C(19)-C(18) 69.0(7) C(6)-C(5)-C(19)-C(18) -53.2(7) N(1)-C(18)-C(19)-O(19) (6) C(17)-C(18)-C(19)-O(19) -52.9(9) N(1)-C(18)-C(19)-C(5) 8.0(7) C(17)-C(18)-C(19)-C(5) 129.7(6) S45

46 Table 23. Crystal data and structure refinement for 19. Empirical formula C 19H 20N 2O Formula weight Temperature 150(2) K Wavelength Å Crystal system Monoclinic Space group P2 1 Unit cell dimensions a = (3) Å α= 90 b = (2) Å β= (10) c = (3) Å γ = 90 Volume (4) Å 3 Z 2 Density (calculated) Mg/m 3 Absorption coefficient mm -1 F(000) 312 Crystal size x x mm 3 Theta range for data collection 4.68 to Index ranges -12<=h<=12, -8<=k<=9, -11<=l<=12 Reflections collected 4369 Independent reflections 2288 [R(int) = ] Completeness to theta = % Absorption correction Semi-empirical from equivalents Max. and min. transmission and Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 2288 / 1 / 202 Goodness-of-fit on F Final R indices [I>2sigma(I)] R1 = , wr2 = R indices (all data) R1 = , wr2 = Absolute structure parameter -0.1(3) Extinction coefficient 0.078(4) Largest diff. peak and hole and e.å -3 S46