J. Am. Chem. Soc., 1996, 118(7), , DOI: /ja952799y

Transcription

1 J. Am. Chem. Soc., 1996, 118(7), , DOI: /ja952799y Terms & Conditions Electronic Supporting Information files are available without a subscription to ACS Web Editions. The American Chemical Society holds a copyright ownership interest in any copyrightable Supporting Information. Files available from the ACS website may be downloaded for personal use only. Users are not otherwise permitted to reproduce, republish, redistribute, or sell any Supporting Information from the ACS website, either in whole or in part, in either machinereadable form or any other form without permission from the American Chemical Society. For permission to reproduce, republish and redistribute this material, requesters must process their own requests via the RightsLink permission system. Information about how to use the RightsLink permission system can be found at Copyright 1996 American Chemical Society

2 American Chemical Society J. Am. Chem. Soc. VI 18 Page 1629 Boger Supplemental Page 1 Supplementary Material (-)-Sandramycin: Total Synthesis and Characterization of DNA Binding Properties Dale L. Boger,* Jyun-Hung Chen and Kurt W. Saionz Department of Chemistry, The Scripps Research Institute North Torrey Pines Road, La Jolla, Caifornia For 44: 'H NMR (CDCl 3, 400 MHz) with irradiation at (D-Ser-NH) led to the collapse of the signal at (M, D-Ser-a-CH) to a dd; irradiation at (Pip-a-CH) led to the collapse of the signal at (Pip-p-CH); irradiation at (D-Ser-a-CH) led to the collapse of the signal at (d, D-Ser-NH) to a singlet and to the collapse of the signal at (D-Ser-p-CH 2 ); irradiation at (D-Ser-p-CH 2 ) led to the collapse of the signal at (m, D-Ser-a-CH) to a d and to the collapse of the signal at (m, Ser-P-OH), to a singlet; irradiation at (Pip-a-CH) led to the collapse of the signal at (Pip-8-CH); irradiation at (D-Ser-p-OH) led to the collapse of the signal at (D-Ser-p-CH 2 ); irradiation at (d, Pip-e-CH) led to the collapse of the signal at (Pip-8-CH); irradiation at (Pip-P and 8-CH) led to the collapse of the signal at (Pip-a-CH) to a singlet, to the collapse of the signal at (Pip-e-CH) to a dd, and to the collapse of the signal at (Pip-a-CH) to a singlet; irradiation at (Pip-8-CH) led to the collapse of the signal at (Pip-e-CH) and to the colapse of the signal at (Pip-y-CH 2 ). For 24: 'H NMR (CDC1 3, 400 MHz) with irradiation at (Gly-NH) led to the collapse of the signal at (dd, Gly-a-CH) to a doublet; irradiation at (D-Ser-NH) led to the collapse of the signal at (D-Ser-a-CH); irradiation at (Sar-a-CH) led to the collapse of the signal at (Sar-a-CH); irradiation at (Pip-a-CH) led to the collapse of the signal at (Pip-p-CH); irradiation at (Val-c-CH) led to the collapse 1

3 American Chemical Society J. Am. Chem. Soc. VI 18 Page 1629 Boger Supplemental Page 2 of the signal at (Val-p-CH) to a septet; irradiation at (Ser-a and p-ch) led to the collapse of the signal at (Ser-NH) to a singlet and to the collapse of the signal at (Ser-p-CH) to a singlet; irradiation at (Ser-p-CH and Gly-a-CH) led to the collapse of the signal at (Ser-NH) to a singlet, to the collapse of the signal at (Ser-a and P- CH) led to a singlet and to the collapse of the signal at (Gly-a-CH); irradiation at (Gly-a-CH) led to the collapse of the signal at (Gly-a-CH); irradiation at (Pip-c- CH) led to the collapse of the signal at (Pip-c-CU) to a singlet; irradiation at (Pipe-CH) led to the collapse of the signal at (Pip-e-CH) to a doublet; irradiation at (Sar-a-CU) led to the collapse of the signal at (Sar-a-CH); irradiation at (Val-p- CH) led to the collapse of the signal at (Val-a-CH) and to the collapse of the signals at and 0.84 (Val-y-CH 3 ) to two singlets; irradiation at (Pip-p-CH) led to the collapse of the signal at (Pip-a-CH) to a singlet. The 2D 'U-'H NOESY NMR spectrum of 24 (CDC1 3, 400 MHz) displayed diagnostic NOE crosspeaks for Gly-NH/pip-a-CH, Gly-NH/Gly-a-CH, Ser-NU/Ser-a-CH, Ser-NH/Val-NCH 3, Sar-a-CH/Sar-NCH 3, Sar-a-CU 3 /Val-NCU 3, Pip-a-CH/Pip-p-CH, Pip-a-CH/Pip-y-CH, Val-a- CH/Val-p-CH, Val-a-CH/Val-y-CH 3, Ser-a-CU/Ser-p-CH, Ser-a-CH/Pip-e-CH, Gly-a-CH/Glya-CH, Pip-c-CU/Pip-e-CH, Pip-e-CH/Pip-y-CH. For 25: 'H NMR (CDC1 3, 400 MHz) with irradiation at (Gly-NH) led to the collapse of the signal at (dd, Gly-a-CH) to a doublet; irradiation at (Ser-NH) led to the collapse of the signal at (d, Ser-a-CH) to a singlet; irradiation at (Sar-a- CH) led to the collapse of the signal at (d, Sar-a-CH) to a singlet; irradiation at (Pip-a-CH) led to the collapse of the signal at (Pip-p-CH); irradiation at 8 4. (Ser-a- 2

4 American Chemical Society J. Am. Chem. Soc. VI 18 Page 1629 Boger Supplemental Page 3 CH and Val-a-CH) led to the collapse of the signal at (Ser-NH) to a singlet and to the collapse of the signal at (Val-p-CH) to a septet; irradiation at (Gly-a-CH) led to the collapse of the signal at (d, Gly-NH) to a singlet, and to the collapse of the signal at (Gly-a-NH); irradiation at (Gly-a-CH) led to the collapse of the signal at (Gly-a-CH); irradiation at (Pip-a-CH)) led to the collapse of the signal at (d, Pipa-CH) to a singlet; irradiation at (Pip-e-CH) led to the collapse of the signal at (Pip-e-CH) to a doublet; irradiation at (Sar-a-CH) led to the collapse of the signal at (d, Sar-a-CH) to a singlet; irradiation at (Val-p-CIH) led to the collapse of the signal at 8 4. (d, Val-a-CH) to a singlet and to the collapse of the signals at and 0.84 (two d, Val-y-CH 3 ) to two singlets; irradiation at (Pip-p-CH) led to the collapse of the signal at (d, Pip-a-CH) to a singlet; irradiation at led to the collapse of the signal at (d split septet, Val-P-CH) to a doublet. For 27: 'H NMR (CDCl 3, 400 MHz) with irradiation at (Gly-NH) led to the collapse of the signal at (dd, Gly-a-CH) to a doublet, irradiation at (Sar-a-CH and Pip-a-CH) led to the collapse of the signal at (d, Sar-a-CH) to a singlet and to the collapse of the signal at (Pip-P-CH), irradiation at (Ser-a-CH) led to the collapse of the signal at (d, Ser-NH) to a singlet and to the collapse of the signal at (dd, Ser-P-CH) to a doublet, irradiation at (Ser-p-CH) led to the collapse of the signal at (dd, Ser-P-CH) to a doublet, irradiation at (Val-a-CH) led to the collapse of the signal at (d split septet, Val-p-CH) to a septet, irradiation at (Ser-p-CH) led to the collapse of the signal at (d, Ser-p-CH) to a singlet, irradiation at (Gly-a-CH) led to the collapse of the signal at (d, Gly-NH) to a singlet and to the collapse of the 3

5 American Chemical Society J. Am. Chem. Soc. VI 18 Page 1629 Boger Supplemental Page 4 signal at (d, Gly-a-CH) to a singlet, irradiation at (Gly-a-CH and Pip-E-CH) led to collapse of the signal at (dd, Gly-a-CH) to a doublet and to the collapse of the signal at (d, Pip-e-CH) to a singlet; irradiation at (Pip-e-CH) led to the collapse of the signal at (dd, Pip-a-CH) to a doublet, irradiation at (Sar-a-CH) led to the collapse of the signal at (d, Sar-a-CH) to a singlet, irradiation at (Val-p-CH) led to the collapse of the signal at (d, Val-a-CH) to a singlet, and to the collapse of the signals at and 0.81 (two doublets, Val-y-CH 3 ) to two singlets, irradiation at (Pip-p-CH) led to the collapse of the signal at (d, Pip-a-CH) to a singlet. 4

6 Table 6. 'H NMR of 25.a chemical shift, 8 (multiplicity, J = Hz) Proton CDC1 3 THF-dg CD 3 OD DMF-d DMSO-d 6b Sandramycin, CDC1 3 Gly-NHI 8.46 (d, 5.2) 8.35 (d, 5.4) 8.44 (d, 6.0) 8.25 (m) 8.52 (d, 4.4) Boc-NH 5.85 (d, 6.1) 5.09 (d, 6.4) 6.46 (d, 7.4) 6.53 (d, 8. Sar-ax-CH 5.35 (d, 16.8) 5.27 (d, 16.6) 5.19 (d, 16.9) 5.14 (d, 16.6) 4.93 (d, 16.6) 5.54 (d, 16.6) Pip-a-CH 5.28 (d, 4.8) 5.31 (d, 5.1) 5.25 (d, 4.8) 5.29 (d, 4.4) 5.01 (m) 5.57 (d, 6.4) Ser-a-CH 4.82 (d, 6.1) 4.78 (m) obscured by H (m) 5.26 (d, 5.0) Val-a-CH 4. (d, 11.0) 4.83 (d, 10.9) 4.75 (d, 11.11) 4.76 (d, 10.9) 4.68 (d, 10.8) 4.87 (d, 11.0) Ser- P -CH 2 4H 4.47 (s) 4.52 (dd, 11.4, 3.0) 4.28 (dd, 11.4, 3.0) 4.45 (m) 4.54 (dd, 11.3, 3.0) 4.40 (m) 4.99 (d, 11.7) 4.43 (d, 11.7) Gly-a-CH 4.41 (dd, 18.0, 5.2) 4.34 (dd, 18.3, 5.7) 4.45 (m) 4.40 (dd, 18.2, 6.0) 4.17 (d, 18.5) 4.43 (d, 11.7) C) Gly-ac-CH 4.03 (d, 18.0) 3.95 (d, 18.3) 4.00 (d, 18.2) 4.07 (d, 18.2) 4.06 (m) 0 Pip-e-CH (ax) 3.90 (app t, 12.0) 3.95 (m) 3.78 (m) 3.84 (app t, 11.6) 4.10 (m) Pip-s-CH (eq) Sar-a-CH 3.61 (d, 12.0) 3.42 (d, 16.8) 3.74 (d, 13.2) 3.60 (d, 16.6) 3.78 (m) 3. (d, 16.9) obscured by H (d, 16.6) 3.82 (d, 16.6) 3.74 (d, 14.5) 3.55 (d, 16.6) 0 Val-NCH 3 6H 2.95 (s) 2.91 (s) 2.99 (s) 3.00 (s) 2.88 (s) 3.12 (s) Sar-NCH 3 6H 2.92 (s) 2.91 (s) 2.96 (s) 2.99 (s) 2.87 (s) 2.94 (s) Val-P-CH 2.13 (dsp, 11.0, 6.5) 2.00 (dsp, 10.9, 6.5) 2.18 (dsp, 11.1, 6.6) 2.12 (dsp, 10.9, 6.6) 2.17 (bs) 2.04 (dsp, 11.0, 6.4) Pip-(CH 2 ) (m) 1.54 (m) 1.65 (m) 1.50 (m) 1.42 (m) 1.73 (m), 1.59 (m), 1.47 (m) Boc 18H 1.40 (s) 1.40 (s) 1.45 (s) 1.41 (s) 1.38, 1.36 (s x 2) Val-y-CH 3 6H 0.98 (d, 6.5) 0.94 (d, 6.5) 0.96 (d, 6.6) 0.93 (d, 6.6) 0.86 (d) 0.92 (d, 6.4) Val-y-CH 6H 0.84 (d, 6.5) 0.81 (d, 6.5) 0.86 (d, 6.6) 0.83 (d, 6.6) 0.76 (d) 0.78 (d, 6.4) 400 MHz. bmultiple conformations, signals detected and attributable to the same conformation detected in other solvents.

7 Figure 6. 1 H NMR (CDCI 3, 400 MHz) of 25 (top) and sandramycin (1, bottom) P PMI ppm 5 4 I ppm L A I ha MJLLt ) ppm ppm l I TI ppm 5 4 ppm A-j -tit_ PPm

8 American Chemical Society J. Am. Chem. Soc. VI 18 Page 1629 Boger Supplemental Page 7 Figure 7. Excitation and emission spectra in 10 mm Tris-HCI, 75 mm NaCI (ph 7.4) with 10 RM agent 120- Excitation spectra of (1) 120- Emission spectra of (1) Ex (300 nm) Em (530 nm) --- Ex (360 nm) -. O nm nm 120- Excitation spectra of luzopeptin A 120 Emission spectra of luzopeptin A Ex (340 rim) ---- Em (530 nm) ---- Ex (360 nm) * - S ~40 40 / tla C 0.II ' nm nm 120- Excitation spectra of (32) 120- Emission spectra of (32) Ex (400 nm) Em(SOnm) Ex (360 nm) S40-40 / nm nm

9 American Chemical Society J. Am. Chem. Soc. VI 18 Page 1629 Boger Supplemental Pa e 8 Table 7. Nucleic Acid Proton Chemical Shift Assignments in the d(gcatgc),- Sandramycin Complex and Their Comparison with Free DNA and Comparable Complexes with Luzopeptin A. d(gcatgc) 2 - d(catg) 2 - d(gcatgc) 2 - Base (5' to 3') Proton d(gcatgc) 3 6 Luzopeptin 3 6 Luzopeptin" Sandramycin Guanosine- I Cytosine-2 Adenosine-3 Thymine-4 Guanosine-5 Cytosine-6 H-8 H-' H-2'/2" H-3' H-4' H-5'/5" H-5 H-6 H-1' H-2'/2" H-3' H-4' H-5'/5" H-2 H-8 H-1' H-2'/2" H-3' H-4' H-5'/5" 5-CH 3 H-6 H-1' H-2'/2" H-3' H-4' H-5'/5" H-8 H-l' H-2'/2" H-3' H-4' H-5'/5" H-5 H-6 H-' H-2'/2" H-3' H-4' H-5'/5" / / ND / ND / ND / ND / ND / / / ND ND / / / ND / /ND / / / / / / / / / / /3.68' / /3.68' / /3.99' / /4.13' / a 3.88/4.15' / /4.04a FPreliminary, tentative assignment.

10 American Chemical Society J. Am. Chem. Soc. VI 18 Page 1629 Boger Supplemental Page 9 Table 8. Sandramycin Proton Chemical Shift Assignments in the d(gcatgc),- Sandramycin Complex and Their Comparison to Free Agent and Comparable Complexes of Luzopeptin A. Proton Luzopeptin (CDC1 3 ) d(gcatgc) 2 - Luzopeptin 36 d(catg) 2 - Luzopeptin3 Sandramycin (CDC 3 ) d(gcatgc) 2 - Sandramycin Quinoline (3.91)a (3.57)' (3.68)' D-Serine-a c c c Sarcosine-a c a c NCH Glycine-a 4.48 ND c a 3.98 ND c Pip-a ( )b (5.14)b (5.18)b I@, y, 6 1.7, 1.6, , 1.50, / c/3.62c Valine-a p Y Y NCH aquinoline C6-OCH 3. bpyr-a. ctentative, preliminary assignments. dnd, not yet determined.

11 (01996 American Chemical Society J. Am. Chem. Soc. V118 Page1629 Boger Supplemental Page 10 j j(,qql-/ob Data Deposition Form TO BE COMPLETED BY AUTHOR ON SUBMISSION OF MANUSCRIPT fournal J. AM. Chem. Soc. N' of Structures 1 Title of Paper (-)-Sandramycin: Total Synthesis and Preliminary DNA Binding Properties Authors Dale L. Boger* and J.-H. Chen For correspondence with author* Tel. N' (619) Fax N*(619) Compound Name or N* 22 Conventional Chemical Diagram H3 O HH Formula (each residue to be formulated separately eg: CsH 4 N 2 0s 2 0) C 5 0 H 8 2 N TO BE COMPLETED BY AUTHOR FOR DATA DEPOSITION Please specify, at start of deposited data: journal, title of paper, authors Please preface each data set by compound name, number or formula Yes O1 Please specify file type (CIFSHELX etc) FLOPPY DISK Yes O Please supply 'text only' standard ASCII file Please specify file type (CIFSHELX etc) Computer type/model Operating system/version 3-- O O Single-sided O1 Double-sided O 360K O1 720K O I.2M O.. Single density Double density O High density O PRINTED LISTING YES TO BE COMPLETED BY EDITOR PUBLICATION Expected year Expected issue number TO BE COMPLETED BY CCDC Data received Coden Dep. N' ' Str. N- Acknowledged Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge, CB2 1EZ, U.K. Tel. N 0 : Fax No: DEPOSITOCHEMCRYS.CAM.AC.UK

12 American Chemical Society J. Am. Chem. Soc. VI 18 Page 1629 Boger Supplemental Page II J I (04q-(( Captions to the figures FIG. 1 ORTEP view of The atoms are ellipsoids. the "Chen" structure. drawn with the 30% probability Fig. 2 Unit cell packing diagram of the "Chen" Hydrogen atoms are omitted for clarity. Fig. 3 Stereoview projection of the structure. "Chen"

13 CD Z0 CD CD CD C25' 08 CD CD,_t 06 C8 C7 0n,23 C Cs 01 -e C16 Cl

14 -5 72 X

15 cz t cz oc cz u (1) I

16 American Chemical Society J. Am. Chem. Soc. VI 18 Page 1629 Boger Supplemental Page 15 Experimental A colorless, plate like crystal (0.04x0.13x0.26 mm) was mounted alongwith the largest dimension and data were collected with a Rigaku AFC6R diffractometer equipped with a copper rotating anode and a highly oriented graphite monochromator. A constant scan speed of 4o/min in w was used and the weak reflections [I<5o(I)] were rescanned to a maximum of 4 times and the counts accumulated to assure good counting statistics. The intensities of three monitor reflections measured after during 51 hrs of X-ray exposure. Unit cell every 200 reflections did not change significantly dimensions and standard deviations were obtained by least squares fit to 25 reflections (50<20< ). The data were corrected for Lorentz and polarization effects and an absorption correction based on psi scan was applied. See Table 1 for cell parameters and other relevant data. The systematic absences (hkl, h+k=2n+l) indicated a choice among the space groups C2, Cm and C2/m. Since the compound is chiral and can only have a two fold site symmetry, C2 was chosen and later confirmed correct because of successful refinement of the structure. Z=2 in this space group suggests that the molecule has a two fold site symmetry. The structure was solved by directi methods using SHELXS86. Nitrogen and and oxygen atoms were refined anisotropically and carbon atoms isotropically by the full matrix least-squares method. The function minimized was Ew(IFI-11Fc ) 2. Hydrogen atoms were refined the wih dea afixe postios oc*2 in the ideal positions with a fixed isotropic U values of 0.08A. A weighting scheme of the form w=1/[a 2(F)+gF 2] with g=0.001 was used. There was no evidence of secondary extinction; therefore it was not applied. The refinement converged to the R indices given in the Table 1 which also includes the A/a and Ap in max the last cycles of refinement. The final difference map was devoid of significant features. All calculations were done on a Silicon graphics Personal Iris 4D/35 and an IBM compatible PC using programs TEXSAN (data reductiong), SHELXS86(structure solution) and SHELXTL (refinement and plotting). Final atomic coordinates are listed in Table 2 and selected bond lengths and bond angles in Table 3. References TEXSAN structure Analysis Package. Molecular Structure Corporation. The Woodlands, TX SHELXS86 G.M.Sheldrick, Acta Crystallogr. A46, (1990). SHELXTL Siemens Analytical Xray Instruments Inc. Madison, Wisconsin,.

17 American Chemical Society J. Am. Chem. Soc. V1 18 Page 1629 Boger Supplemental Page 16 Table 1. Summary of crystal data, data collection and structural refinement for Crystal Data Unit Cell Parameters Volume Crystal System Space Group Empirical Formula Formula weight Z; F(000) Density(calc.) Absorption Coefficient (g) Absorption Correction Data Collection Radiation Monochromator Temperature (K) 20 Range Scan Type Scan Speed Scan width Scan time/ background time Index Ranges Total reflections Collected Independent Reflections Unique data used (m) a = (3), b = 7.291(1), c = (2) A #= 96.63(1) 2894(1) A 3 Monoclinic C2 (No. 5, C 2 3 ) C50 H52 N ; Mg/m mm- 1 Transmission factors: CuKa (X = A) Highly oriented graphite crystal to Constant; 4.00 /min tanO 2:1 in w;(for details see text) 0 h!21, 0 k 8, (Rint = 0.00%) 1530 (F > 4.0a(F)) Solution and Refinement No. of Parameters Refined (n) 217 Data-to-Parameter Ratio (m/n) 7.1:1 Final R Indices (obs. data) R = 7.02 %, wr = % Goodness-of-Fit (S) 2.51 Largest shift/error (A/a) Largest Difference Peak (Ap )0.35 ea -3 Largest Difference Hole ea R=(E 11gI-FI I/E IFgI), of wr=( w( F B-F )2/ EW1II12]h, S=[Ew( IF l-iifc1 )2/(m-n)]h

18 American Chemical Society J. Am. Chem. Soc. VI 18 Page 1629 Boger Supplemental Page 17 Table 2. Atomic coordinates (xlo 4) and equivalent isotropic 4j displacement coefficients (A x103 x y z U(eq) 0(1) 5859(3) (3) 84(3) 0(2) 6270(4) 7937(18) 9386(4) 97(3) 0(3) 5108(4) 6165(17) 7455(3) 71(3) 0(4) 6523(3) 7686(18) 6492(3) 75(3) 0(5) 5711(3) 5346(18) 4448(3) 60(2) 0(6) 6951(3) 8518(16) 3826(3) 66(2) 0(7) 6000(4) 11704(18) 2512(4) 99(4) 0(8) 5825(3) 9259(17) 1881(3) 64(2) N(l) 5433(4) 6888(21) 8639(3) 75(3) N(2) 5364(3) 8883(18) 7044(3) 52(3) N(3) 5860(3) 6179(18) 5712(3) 51(2) N(4) 6886(3) 5225(18) 4381(3) 49(2) N(5) 6810(3) 7516(18) 28(3) 49(2) C(1) 7072(6) 4513(29) 9859(6) 118(5) C(2) 6109(7) 2424(28) 10052(7) 117(5) C(3) 6172(8) 5474(34) 10539(7) 148(6) C(4) 6316(5) 4376(22) 9969(5) 76(3) C(5) 5891(6) 6719(21) 9176(5) 68(3) C(6) 5431(4) 8476(20) 8228(4) 54(2) C(7) 5293(4) 7760(20) 7541(4) 51(2) C(8) 5719(5) 10673(21) 7096(5) 70(3) C(9) 5382(6) 12058(24) 6616(5) 84(3) C(10) 5309(5) 11272(23) 5938(5) 76(3) C(11) 4899(4) 9467(19) 5916(4) 55(2) C(12) 5243(4) 95(18) 6405(4) 45(2) C(13) 5933(4) 7328(20) 6208(4) 53(2) C(14) 6462(4) 5420(20) 5434(4) 56(2) C(15) 6322(4) 5336(20) 4712(3) 46(2) C(16) 7616(4) 5264(20) 4668(4) 59(2) C(17) 6779(4) 5295(21) 3688(4) 52(2) C(18) 6850(4) 7285(19) 3450(4) 46(2) C(19) 6666(5) 6008(21) 2365(4) 69(3) C(20) 6895(4) 9341(20) 2558(4) 51(2) C(21) 7391(4) 9554(20) 2035(4) 57(2) C(22) 7494(5) 11571(23) 1855(5) 77(3) C(23) 8100(6) 8664(30) 2237(6) 115(5) C(24) 6194(5) 10276(22) 2328(4) 63(2) C(25) 5116(5) 9881(22) 1632(4) 70(3) * Equivalent isotropic U defined as one third of the trace of the orthogonalized U.. tensor, i.e, U =1/3Y LU..a.*a.*a.*a.

19 American Chemical Society J. Am. Chem. Soc. VI 18 Page 1629 Boger Supplemental Page 18 Table 3. Bond lengths (A) and bond angles (o i I (a q -I 0(1)-C(4) 0(2)-C(S) 0(4)-C(13) 0(6)-C(18) 0(8)-C(24) N(1)-C(5) N(2)-C(7) N(2)-C(12) N(3)-C(14) N(4)-C(16) N(5)-C(18) N(5)-C(20) C(2)-C(4) C(6)-C(7) C(8)-C(9) C(10)-C(11) C(12)-C(13) C(17)-C(18) C(20)-C(24) C(21)-C(23) (12) (18) (10) (15) (14) (12) (15) (12) (12) (9) (10) (18) (25) (13) (18) (20) (13) (20) (14) (17) 0(1)-C(5) 0(3)-C(7) 0(5)-C(15) 0(7)-C(24) 0(8)-C(25) N (1) -C (6) N(2)-C(8) N(3)-C(13) N(4)-C(15) N(4)-C(17) N(5)-C(19) C(1)-C(4) C(3)-C(4) C(6)-C(25A) C(9)-C(10) C(11)-C(12) C(14)-C(15) C(20)-C(21) C(21)-C(22) C(25)-C(6A) (15) (19) (9) (19) (11) (18) (18) (15) (10) (10) (17) (15) (23) (17) (16) (15) (10) (13) (21) (17) C(4)-0(1)-C(5) C(5)-N(1)-C(6) C(7)-N(2)-C(12) C(13)-N(3)-C(14) C(15)-N(4)-C(17) C(18)-N(5)-C(19) C(19)-N(5)-C(20) 0(1)-C(4)-C(2) 0(1)-C(4)-C(3) C(2)-C(4)-C(3) 0(1)-C(5)-N( 1) N(1)-C(6)-C(7) C(7)-C(6)-C(25A) 0(3)-C(7)-C(6) N(2)-C(8)-C(9) C(9)-C(10)-C(11) N(2)-C(12)-C(11) C(11)-C(12)-C(13) 0(4)-C(13)-C(12) N(3)-C(14)-C(15) 0(5)-C(15)-C(14) N(4)-C(17)-C(18) 0(6)-C(18)-C(17) N(5)-C(20)-C(21) C(21)-C(20)-C(24) C(20)-C(21)-C(23) 0(7)-C(24)-0(8) 0(8)-C(24)-C(20) 123.3(8) 122.0(11) 117.1(11) 122.5(7) 119.3(6) 122.1(11) 119.1(7) 105.6(9) 109.1(11) 110.1(13) 109.6(11) 106.2(11) 111.5(7) 118.6(10) 112.8(9) 110.1(10) 111.9(10) 111.8(7) 123.5(10) 111.3(7) 120.1(7) 110.6(10) 120.3(8) 117.1(10) 108.4(8) 110.9(9) 124.2(10) 110.1(12) C(24)-0(8)-C(25) C(7)-N(2)-C(8) C(8)-N(2)-C(12) C(15)-N(4)-C(16) C(16)-N(4)-C(17) C(18)-N(5)-C(20) 0(1)-C(4)-C(1) C(1)-C(4)-C(2) C(1)-C(4)-C(3) 0(1)-C(5)-0(2) 0(2)-C(5)-N(1) N(1)-C(6)-C(25A) 0(3)-C(7)-N(2) N(2)-C(7)-C(6) C(8)-C(9)-C(10) C(10)-C(11)-C(12) N(2)-C(12)-C(13) 0(4)-C(13)-N(3) N(3)-C(13)-C(12) 0(5)-C(15)-N(4) N(4)-C(15)-C(14) 0(6)-C(18)-N(5) N(5)-C(18)-C(17) N(5)-C(20)-C(24) C(20)-C(21)-C(22) C(22)-C(21)-C(23) 0(7)-C(24)-C(20) 0(8)-C(25)-C(6A) 117.9(11) 124.8(8) 116.2(8) 124.5(6) 115.8(6) 118.7(10) 110.2(9) 110.7(13) 111.1(12) 127.4(10) 122.9(14) 112.4(8) 121.2(9) 120.1(12) 110.8(13) 111.6(8) 110.2(6) 121.2(9) 115.2(7) 122.4(7) 117.6(6) 123.4(12) 116.3(10) 113.3(9) 112.2(10) 110.2(10) 125.7(10) 110.4(11) Symmetry Equivalent positions: A= 1-x, y 1-z

20 American Chemical Society J. Am. Chem. Soc. VI 18 Page 1629 Boger Supplemental Page 19 1L~~4Ll4~ TORSION ANGLES FOR C5 C5 C5 C4 C4 C6 C6 C5 Ca C8 Ni Ni C7 C8 C9 C7 C7 C8 C8 C1O C1O C14 C14 Cii Cii C13 C16 C16 C1 7 C17 N3 N3 C15 C16 C19 C19 N4 N4 C18 C18 C19 C19 C24 C24 C25 C25 C21 C N1 N1 N1 C6 C6 C8 C9 C10 Cii Cii N3 N3 N3 N4 N4 N4 N4 C14 C14 N4 N4 NS C17 C17 C C4 C4 C4 C5 C5 CS C5 C6 C7 C7 C7 C7 C7 C7 C8 C8 C9 C10 Cii C13 C13 C13 C13 C13 C13 C14 C15 C15 C15 C15 C15 C15 C17 C17 C18 Ci8 C18 C18 C18 c18 C21 C21 C21 C21 C24 C24 C24 C24 C24 C24 Cl C2 C3 02 Ni C7 03 C6 03 C6 03 C9 C9 CI Cii Cii C13 Cii C13 C N3 04 N3 C15 05 C14 05 C14 05 N4 C18 C18 06 C17 06 C17 06 C21 C24 C21 C24 C22 C23 C22 C CHEN CRYSTAL

21 American Chemical Society J. Am. Chem. Soc. VI 18 Page 1629 Boger Supplemental Page 20 Table 4. Anisotropic displacement coefficients (A x103 U 1 1 U 2 2 U 3 3 U 1 2 U 1 3 U 2 3 0(1) 0(2) 0(3) 0(4) 0(5) 0(6) 0(7) 0(8) N(1) N(2) N(3) N(4) N(5) 72(4) 106(6) 97(5) 52(3) 52(3) 92(4) 89(5) 53(3) 61(4) 59(4) 47(4) 47(3) 71(4) 123(8) 88(7) 56(5) 96(6) 71(5) 53(5) 56(6) 81(5) 109(8) 48(5) 54(5) 54(5) 40(5) 54(4) 88(5) 59(4) 76(4) 57(3) 52(3) 154(7) 58(3) 50(4) 49(4) 52(4) 47(3) 37(4) -8(5) 8(5) -15(4) -1(4) 3(4) -3(4) 6(5) 6(4) -13(5) -14(4) 2(4) 0(4) -7(4) -13(3) -29(4) 8(3) 2(3) 6(3) 5(3) 23(5) 8(3) -12(3) 9(3) 11(3) 11(3) 2(3) 10(5) -14(5) -3(4) -26(4) 2(4) -9(4) -20(5) 8(4) 3(5) -14(4) -4(4) 5(4) 2(3) The anisotropic displacement exponent takes the form: -2w 2(h 2a*2 U 11+k 2b*2 U 22+12c*2 U33 +2hka*b*U 2+2hla*c*U 3+2klb*c*U23

22 American Chemical Society J. Am. Chem. Soc. VI 18 Page 1629 Boger Supplemental Page 21 Table 5. H-Atom coordinates (xlo 4) and isotropic displacement coefficients (Ax103) x y z U H (1A) H (3A) H(1B) H(1C) H (1D) H(2A) H (2B) H(2C) H (3B) H (3C) H(3D) H(6A) H (8A) H (8B) H (9A) H(9B) H(10A) H(10B) H(11A) H(11B) H(12A) H(14A) H(14B) H(16A) H(16B) H(16C) H(17A) H(17B) H(19A) H(19B) H(19C) H(20A) H(21A) H(22A) H(22B) H(22C) H(23A) H(23B) H(23C) H(25A) H(25B)