Supporting Information To: Synthesis of a xylo-puromycin Analogue Benoît Y. Michel, Kollappillil S. Krishnakumar and Peter Strazewski* Laboratoire de Synthèse de Biomolécules, Institut de Chimie et Biochimie Moléculaires et Supramoléculaires (UMR ), Université Claude Bernard Lyon 1, 9, Villeurbanne, FRACE. Tel: (+33) 7--3 E-mail: strazewski@univ-lyon1.fr Table of contents Pages General methods and experimental procedures for the synthesis of,, 9 and 10... MR spectra of:... 11...1 17...1,-di-n-butylformamidine dimethylacetal (distilled)...3 7... 31...3 0 9...1...9 10...7 1 Page 1
General Methods 1 H-MR spectra (300 and 00 MHz) were obtained from solutions in CDCl 3 and CD 3 D, with the residual protonated solvent signals as internal reference (7. ppm for CHCl 3, 3.31 ppm for CD HD). The chemical shifts δ H are given in ppm; the coupling constants J are given in Hertz (Hz); the signals are described as follows: ps. = pseudo, br. = broad, s = singlet, d = doublet, t = triplet, q = quartet, m = multiplet. 13 C-MR spectra (7 and 1 MHz) were measured in CDCl 3 ; δ C (central signal) = 7 ppm and in CD 3 D δ C (central signal) = 9. ppm. The assignments of 1 H- and 13 C-MR signals were achieved with the help of D/H exchange, CSY, HSQC, HMBC and DEPT experiments. Mass spectra (MS and HRMS) were obtained using Fast Atom Bombardment (FAB from CH Cl or H /MeH 9:1) and Electro Spray Ionization (ESI, from CH Cl or DMS). Thin Layer Chromatography (TLC) was performed on pre-coated silica gel F plates with fluorescent indicator. The compounds were visualized using UV light ( nm). Free amines were visualised on TLC plates by spraying with 0% ninhydrin solutions in ethanol, followed by heating. ucleosides were visualised on TLC plates by subsequent spraying with concentrated H S followed by % naphtoresorcinol (for the ribose intermediates) or phosphomolybdic acid solutions in ethanol, followed by heating. Column chromatography was performed with flash silica gel (10-3 µm). Page
Experimental procedures ',-Anhydro-adenosine (). To a suspension of adenosine 3 ( g, 1.7 mmol) in dry CH 3 C (30 ml) were sequentially added H /CH 3 C (1:9; ml, mmol), then α-acetoxyisobutyryl bromide (11. ml, 7 mmol) and stirring was continued at ambient temperature. A clear solution resulted after min (and adenine as a fine colorless precipitate began to separate shortly thereafter). After 1 h, saturated ahc 3 solution (0 ml) was added cautiously and the solution was extracted with EtAc ( x 0 ml). The combined organic phase was washed (brine), dried (MgS ), filtered, and evaporated to give a colorless solid foam, which was dissolved in dry MeH (10 ml) and stirred for 1 h with 0 ml of Dowex 1 x (H ) resin (previously exchanged against Cl, washed with dry MeH and thoroughly dried under oil pump vacuum). The resin was filtered and rinsed with MeH. Evaporation of the combined filtrate and crystallization of the residue (EtH) gave microcrystalline epoxide (. g, 91%). C 10 H 11 3 (9.7). R f (DCM/MeH 9:1) = 0.17. 1 H-MR (d -DMS, 300 MHz): δ H = 3. (dd, 1 H, J = 11.7 Hz, 3 J =.0 Hz, H A '), 3. (dd, 1 H, J = 11.7 Hz, 3 J =. Hz, H B '),.19 (t, 1 H, 3 J =.1 Hz, H'),.3 (d, 1 H, 3 J =. Hz, H),.7 (d, 1 H, 3 J =. Hz, H'),.09 (br. s, 1 H, H),.3 (s, 1 H, H), 7.3 (br. s, H, H ),.19 (s, 1 H, H),.3 (s, 1 H, H). 13 C-MR (d - DMS, 300 MHz): δ C = 7. (C'),.7 (C3 ), 0.9 (C'), 1.1 (C'),.0 (C), 11.7 (C) 139. (C), 19.1 (C), 1.7 (C), 1.0 (C). LRMS (ESI + ): m/z = 0.0 (calculated for [M+H] + : 0.1). ',-Anhydro-'--(tert-butyldiphenylsilyl)-adenosine(). TBDPSCl (3.3 ml, 3.7 g, 13.mmol) was added to epoxide (3. g, 1. mmol) in anhydrous pyridine ( ml), and the solution was stirred for 1 h at ambient temperature. H (3 ml) was added, stirring was continued for 30 min, and the volatiles were evaporated. The residue was partitioned (H /CHCl 3 ), and the organic phase was washed [(H, x 100 ml); Page 3
ahc 3 /H ; brine] and dried (MgS ). The volatiles were evaporated to give in almost quantitative yield, which was used in the next step without chromatography. C H 9 3 Si (7.3). R f (DCM/MeH 9:1) =0.70. 1 H-MR (CDCl 3, 300 MHz): δ H = 1.03 (s, 9 H, Si-C(CH 3 ) 3 ), 3.73 (dd, 1 H, J = 10. Hz, 3 J = 7., H A '), 3. (dd, 1 H, J = 10. Hz, 3 J =.3 Hz, H B '),.11 (d, 1 H, 3 J =.3 Hz, H),.0 (ps. t, 1 H, 3 J =.3, 7. Hz, H'),.0 (d, 1 H, 3 J =.3 Hz, H'),.01 (br. s, H, H ),.1 (s, 1 H, H), 7.9 7.3 (m, H, H-m-Ar & H-p-Ar), 7.3 7.1 (d, H, 3 J = 7. Hz, H-o-Ar), 7. (s, 1 H, H),.3 (s, 1 H, H). 13 C-MR (CDCl 3, 7 MHz): δ C = 19.0 (Si-C(CH 3 ) 3 ),.7 (3 C, Si-C(CH 3 ) 3 ), 7.9 (C'),.9 (C3 ), 3. (C'), 0.7 (C'), 3.9 (C), 119.7 (C), 17.7 ( C, C-m-Si-Ph), 19. ( C, C-p-Si-Ph), 13., 13. ( C, C-i-Si- Ph), 13.3 ( C, C-o-Si-Ph), 13.9 (C), 19.1 (C), 1.9 (C), 1.7 (C). LRMS (ESI + ): m/z =. (calculated for [M+H] + :.). 9-['--tert-Butyldiphenylsilyl---(α--fluorenylmethoxycarbonyl-p-methoxy-L-phenylalanyl)amido--deoxy-β-D-xylofuranos-1- yl]adenine (9). The procedure to obtain 9 (7 mg, 0% from 93.9 mg of 7) is the same as for. 1 H-MR (CDCl 3, 300 MHz): δ H = 0.9 (s, 9 H, Si-C(CH 3 ) 3 ),.79 (dd, 1 H, J = 13. Hz, 3 J =. Hz, Hβ1),.9 (dd, 1 H, J = 13. Hz, 3 J = 9.0 Hz, Hβ), 3.1 (s, 3 H, CH 3 ), 3. 3.9 (m, H, H A ', H B '),.0.10 (m, 3 H, H aliph. Fl., H', CH -Fl.),.13. (m, H, Hα, CH -Fl.),.37. (m, 1 H, H'),.0 (d, 1 H, 3 J =. Hz, H),.7 (d, 1 H, 3 J =. Hz, H),. (d, H, 3 J =. Hz, H-o-Ph(Me)),.9 (d, H, 3 J =. Hz, H-m-Ph(Me)), 7.11 (ps. t, H, 3 J = 7., 7. Hz, H-m -Fl.), 7.19 7. (m, H, H-m-Si-Ph, H-p-Si-Ph), 7.31 7.39 (m, H, H-p 3 -Fl.), 7. 7. (m, H, H-o 1 -Fl., H-o-Si-Ph), 7.7 (d, H, 3 J = 7. Hz, H-m -Fl.),.11 (s, 1 H, H),.1 (s, 1 H, H). 13 C-MR (CD 3 D, 7 MHz): δ C =. (3 C, Si-C(CH 3 ) 3 ), 37.7 (Cβ), 7. (CH aliph. Fl.),.7 (Me), 7. (C),. (Cα),.3 (C'), 7. (CH -Fl.), 1. (C'),.0 (C'), 93. (C), 113. ( C, C-o-Ph(Me)), 119.9 ( C, C-m -Fl.), 1.0 ( C, C-o 1 -Fl.), 1.7 (C), 1 ( C, C-m -Fl.), 17.3 ( C, C-p 3 -Fl.), 17.9 ( C, C-m-Si-Ph), 1.0 (C-p- Page
Ph(Me)), 19. ( C, C-p-Si-Ph), 130. ( C, C-m-Ph(Me)), 13., 13.9 ( C, C-o-Si-Ph), 11. (C), 13.0 (C), HRMS (ESI + ): m/z = 90.39 (calculated for [M+H] + : 90.3). 9-(-Bromo-'--tert-butyldiphenylsilyl--deoxy-β-D-xylofuranos-1-yl)adenine (10). Et 3 (1 µl,.0 mg, 0.3 mmol) and Me BBr/CH Cl (0.33 M, 7. ml,. mmol) were added to a cold (-7 C) solution of the protected epoxide (0 mg, 1. mmol) in CH Cl (3 ml). Stirring was continued for 1 h, and the reaction mixture was poured into a stirred solution of aqueous saturated ahc 3 /H. The organic layer was separated, and the aqueous layer was extracted (CH Cl ). The combined organic phase was washed (brine) and dried (MgS ). Evaporation of volatiles gave a white solid (1mg, 9%) that was crystallized (THF/MeC) to give the bromo product (1 mg, 9%). C H 30 Br 3 Si (.). Mp (uncorr.): 09 11 C. R f (EtAc/CyHex :1) = 0.0. 1 H-MR (d -DMS, 300 MHz): δ H = 1.00 (s, 9 H, Si-C(CH 3 ) 3 ), 3.9 (dd, 1 H, J = 11.0 Hz, 3 J =. H A '),.03 (dd, 1 H, J = 11.0 Hz, 3 J =. Hz, H B '),.3 (dd, 1 H, 3 J =.,. Hz, H'),.0 (dd, 1 H, 3 J =.1,.3 Hz, H),.9 (q ddd, 1 H, 3 J =.1,.9 Hz, H'),.9 (d, 1 H, 3 J = 3.9 Hz, H),. (d, 1 H, 3 J =.1 Hz, H), 7.33 (br. s, H, H ), 7.3 7.7 (m, H, H-m-Ar & H-p-Ar), 7.3 7.7 (m, H, H-o-Ar),.09 (s, 1 H, H),.1 (s, 1 H, H). 13 C-MR (d -DMS, 7 MHz): δ C = 1. (Si-C(CH 3 ) 3 ),. (3 C, Si-C(CH 3 ) 3 ), 3.1 (C),. (C'), 79.9 (C'), 0.0 (C'),. (C), 11.9 (C), 17.9, 1.0 ( C, C-m-Si-Ph), 130.0 ( C, C-p-Si-Ph), 13., 13.7 ( C, C-i-Si-Ph), 13.0, 13.1 ( C, C-o-Si-Ph), 13.3 (C), 19.3 (C), 1. (C), 1.0 (C). LRMS (ESI + ): m/z = 70.1 (calculated for [M+H] + : 70.1). Page
3. 3.7 3. 3.3 3.7.7..33..11.19.177 3.0.0.09.00 1 H MR H' H H' ppm (t1).0 ' DMS ' ' H' A H' B H H Page.13.09 1.00 H 0.9.0. H 1.03 7.30 H.1.17.3 H H.0 0.9 1.03
ppm (t1) 10 100 1.71 139..0 1.13 0.3.71 7.71 C C DEPT MR H ' ' ' H C C' C' C C' Page 7
ppm (t1) 10 100 0 1.0 1.71 19.119 139.3 11.9.0 1.13 0..71 7.71 39.9 39.70 39.30 39.1 3.7 C C C C 13 C MR H ' ' C ' H C C' C' C C' DMS Page
3.0.0.0.0 CSY H ' ' ' H.0 ppm (t1 ppm (t).0.0.0.0 Page 9
0 100 HSQC H ' ' ' H 10 ppm (t1 ppm (t).0.0.0.0 3.0 Page 10
0 100 HMBC H ' ' ' H 10 ppm (t1 ppm (t).0.0.0.0 Page 11
1.0 t Bu H ' 9.0 1.0.0 Page 1 3.71 3.7 3.7 3.70 3.3 3.9 3.7 3.3..07.00.33.11.110 1 H MR TBDPS H' H' ' ' H H' A H' B.0 0.9.01 3.0.0.0.0.1.00 H H 1.9 1.00 7.10 7. 7.3 7.3 7.3 7.371 7.33 7.337 7.31. 7.7 7.77 7.7 7.7 CHCl 3 H H x H-m-Ph x H-p-Ph x H-o-Ph.3.03 1. 1.0 1.03.0 ppm (t1)
ppm (t1) 10 100 0 1.91 13.93 13.7 13.71 19.33 19. 17.701 17.7 3.93 0.97 7 3.19.93 7.7.93. C x H-m-Ph x H-p-Ph x H-o-Ph C C DEPT MR C' TBDPS ' ' C C' CHCl 3 C' ' H t Bu Page 13
ppm (t1) 10 100 0 1.71 1.90 19.0 13.93 13. 13.77 13.70 13.7 13.39 19.3 19.1 17.700 17. 17.7 119.707 3.93 0.9 77.3 700 7.7 3.19.91 7..93 19.001 C C C x C-m-Ph x C-p-Ph x C-o-Ph x C-i-Ph C C 13 C MR TBDPS ' ' CDCl 3 ' H C C' C' C C' t Bu C- t Bu Page 1
1.0.0 3.0.0.0 CSY TBDPS ' ' ' H.0.0 ppm (t1.0.0.0.0 3.0.0 1.0 Page 1
0 100 HSQC TBDPS ' ' ' H 10 ppm (t1.0 ppm (t).0.0.0 3.0.0 1.0 Page 1
0 100 HMBC TBDPS ' ' ' H 10 ppm (t1.0 ppm (t).0.0.0 3.0.0 1.0 Page 17
1.3 1.00 0.99 0.91 0.97 0 9 1.30 3.07.0.00.9.07 1.971 3.0 3.7.3.30.1.01.09..7.3.3.31.00 3.9 3.971 3.901 3.7 3. 3.0.91.99.3.3 7.7 7. 7.33 7.1 7.3 7.3 7.11 7.3 7.31 7.33.1.13 x H-m-Ph x H-p-Ph H t Bu H' x H-o-Ph 1 H MR 3 H H TBDPS ' H ' H H H ' H DMS EtAc H' A H' B H H' EtAc 9.01 1. 1.31.10 1.0 1.00 1.00..30 0.97 0.99 Page 1 alkane 1.0.0.0.0.0 3.0.0 ppm (t1)
ppm (t1) 10 100 0 1.71 13.0 13.101 13.007 19.979 17.91 17.7 79.3 71.007.99 39.9.17 C x C-o-Ph x C-m-Ph x C-p-Ph C C C' DEPT MR C' C TBDPS ' ' 3 C' ' H DMS H t Bu Page 19
ppm (t1) 10 100 0 1.031 1.7 19.37 13. 13.101 13.009 13.71 13.3 19.979 17.93 17.77 11.7 7.39 79.3 71.007.99 0. 39.9 39.70 39.30 39.11 3.73 3.9.17 1.73 C C C x C-o-Ph x C-m-Ph x C-i-Ph x C-p-Ph C C 13 C MR TBDPS ' ' 3 C ' H C' C' H C C' DMS t Bu C- t Bu Page 0
CSY TBDPS ' ' 3 ' H H 1000 00 pt (t1) pt (t) 00 1000 Page 1
0 100 HSQC TBDPS ' ' 3 ' H H 10 ppm (t1 ppm (t).0.0.0.0 3.0.0 1.0 Page
0.9 0.9 1. 0.91 1.73 1.97 1.31 1.31 1.37 1.03 1.7.3..11 1 H MR (CH CH CH CH 3 ) Me Me (CH CH CH CH 3 ).9...3.0.00 1.0 1.00 3.99.3.00 3.00 3.0 Page 3 (CH CH CH CH 3 ) (CH CH CH CH 3 ) xme.07.0 RCH(Me) 1.00 ppm (t1)
11.1 3.9 0 30.937 0. 13. 13 C MR (CH CH CH CH 3 ) (CH CH CH CH 3 ) RCH(Me) Me Me (CH CH CH CH 3 ) (CH CH CH CH 3 ) x Me CDCl 3 ppm (t1) 100 0 Page
1 0 371 3 07 99 97 97 3.7 3.73 3.77 3.737 3.71 3. 3. 3.37 3.1 3.19 3.39 3.370 1.90 1. 1.0 1.31 1.1 1.3 1.07 1.39 1.390 1.30 3.9 3.90 3.93 3.91 3.900 3. 3.3 3..7.1.3.1.390.37.3.91.901..11.797.7 7.39 7.390 7.39 7.3 7.3 9.00.0 7. 7.9 7. 7. 7.3 7.1 Bu H H t Bu 7 1 H MR (CH CH CH CH 3 ) x H-o-Ph x H-m-Ph x H-p-Ph CH-dbf 3 TBDPS ' ' ' (CH CH CH CH 3 ) H CHCl 3 (CH CH CH CH 3 ) H (CH CH CH CH 3 ) H' A H' B H H' H' TMS H 1..17..3.1. 1.09 1.0 0.9 1.0 0.0 7.1.0 0.99 1.00 1.09.0 0.0 ppm (t1) Page
ppm (t1) 10 100 0 1.77 1.0 139.3 13.31 13.0 13.3 19. 17.1 17.70 1.9. 30.9 9.1. 0.11 19.709 13. 13.7 90.3 1.333 79.70.1.13 x C-o-Ph x C-m-Ph x C-p-Ph CH-dbf C C 7 DEPT MR TBDPS 3 ' ' ' H Bu t Bu (CH CH CH CH 3 ) C C' C' C C' (CH CH CH CH 3 ) (CH CH CH CH 3 ) (CH CH CH CH 3 ) Page
.1.13 1.9.3 30.9 9.1. 0.139 19.70 19.0 13. 13. t Bu 7 13 C MR (1) TBDPS ' ' 3 ' H Bu (CH CH CH CH 3 ) (CH CH CH CH 3 ) (CH CH CH CH 3 ) C- t Bu C C' (CH CH CH CH 3 ) 70 ppm (t1) 0 0 0 30 0 Page 7
10 ppm (t1) 10 10 130 10 110 100 90 0 19.91 1.7 1.01 10.19 139.30 13.30 13.79 13.7 13.7 19.00 17.71 1.77 90.3 1.33 79.70 77. 700 7.77 CH-dbf C x C-o-Ph x C-m-Ph x C-p-Ph C C C x C-i-Ph C 7 13 C MR () TBDPS 3 ' ' H ' Bu C CDCl 3 C' C' Page
1.0.0 3.0.0.0 Bu.0 7 CSY TBDPS ' ' 3 ' H.0 9.0 ppm (t1 ppm (t) 9.0.0.0.0.0 3.0.0 1.0 Page 9
0 7 HSQC TBDPS ' ' 3 ' H Bu 100 10 ppm (t1 ppm (t) 9.0.0.0.0.0 3.0.0 1.0 Page 30
0 100 7 HMBC TBDPS ' ' 3 ' H Bu 10 ppm (t1 ppm (t) 9.0.0.0.0.0 3.0.0 1.0 Page 31
0.93 0.99 0.9 1.33 1.7 1. 1.0 1.39 1.3 1.37 1.37 1.9 1.7 1. 1.79 1.70.7..9.91.901 3.3 3.10 3.3 3.09 3.713 3.739 3.73 3.91 3.99 3.90 3.93.130.10.9.173.7.3.97.1.0.79.79.73.7.71.70..3 t Bu Page 3 (CH Me CH CH CH 3 ) (CH CH CH CH 3 ) 1 H MR (1) 3 1 H (CHCHCHCH3) Me (CH CH CH CH 3 ) β dbf α H H ' ' ' H RC()CH Fluorenyl H-aliph. Fl. H' CH α H' H' A H β1 H β H' B H 1.0..0 1.91 1..91.91 1.01 1.1 1.77.90 1.00 1.0.0.0 3.0.0 ppm (t1) alkane
..3..77.73 1 H MR () β Me H dbf α H H H HFmoc H 1.9 0.93.0.1 7.199 07 7..91. 7.33 7.319 7.300 7.9 7. 7.7 7. 1.9 1.9.0 7.3 7.377 11.33 7.9 7.3 0.0 7.70 7. 7.7 7. 7.7 7.1 7.7.30. 7.97 7.73. 1 3 ' ' ' H Page 33 x H-m-Ph(Si) x H-p-Ph(Si) x H-m -Fl x H-p 3 -Fl x H-m-Ph(Me) x H-o-Ph(Me) x H-o-Ph(Si) x H-o 1 -Fl H x H-m -Fl H -H.0 0. 1.1.0 9.017 CH-dbf 0.9 9.0 ppm (t1)
ppm (t1) 90 0 70 0 0 0 30 0 10 91.7 0. 0...39 7.173.703.03.00 7.101.3 3. 30.91 9.1.70 0.1 19.737 13.90 13. C 3 1 C' C' H ' ' DEPT MR (1) H β Me α dbf H H ' Me CH Fluorenyl C CH α C' RC()CH Fluorenyl (CH CH CH CH 3 ) t Bu (CH CH CH CH 3 ) CH β (CH CH CH CH 3 ) (CH CH CH CH 3 ) alkane Page 3
1.37 19.3 11.31 13.7 130.310 19.7 17.3 17. 17.1 11 1.0 119.91 119.9 113.0 3 1 DEPT MR () x C-o-Ph(Si) x C-p-Ph(Si) x C-m-Ph(Si) x C-p 3 -Fl H H ' ' α β H ' H dbf Me x C-m-Ph(Me) x C-m -Fl x C-o-Ph(Me) x C-m -Fl x C-o 1 -Fl CH-dbf C C 10 ppm (t1) 10 10 130 10 110 Page 3
90 ppm (t1) 0 0 70 0 0 0 30 91..700 0.1 19.73 1.99 13.90 13.1 0. 0. 77. 7 700 7.77..39 7.17.70.03.00 7.10.3 3.31 30.919 9. 9.0 C t Bu (CH CH CH CH 3 ) (CH CH CH CH 3 ) C- t Bu CDCl 3 C' C' 3 1 13 C MR (1) RC()CH Fluorenyl Me H H ' ' α β H (CH CH CH CH 3 ) CH Fluorenyl ' H dbf Me (CH CH CH CH 3 ) C' CH α C CH β alkane Page 3
ppm (t1) 170 10 10 10 130 10 110 171.373 1.9 1.99 1.3 1.33 11.1 10.0 13.7 13.3 11.7 13. 13.71 13.0 130.317 19.771 17.779 17. 17. 119 1.0 1.03 119.91 113.11 3 1 H β 13 C MR () H ' ' α H H ' C-i-Ph(Me) C CH-dbf -HC()R RC()CH Fluorenyl Me dbf C C x C-o-Ph(Si) x C-m-Ph(Si) x C-m-Ph(Me) x C-p-Ph(Si) x C-p 3 -Fl C x C-o -Fl x C-m -Fl x C-o-Ph(Me) C-p-Ph(Me) x C-m -Fl x C-o 1 -Fl x C-i-Ph(Si) x C-i-Fl C Page 37
ppm (t) 1.0.0 3.0.0.0.0.0 9.0 1.0.0 3.0.0.0.0.0 9.0 ppm (t1 CSY ' ' ' dbf H H H Me H 1 3 α β Page 3
ppm (t) 1.0.0 3.0.0.0.0.0 9.0 0 100 10 ppm (t1 HSQC ' ' ' dbf H H H Me H 1 3 α β Page 39
ppm (t) 1.0.0 3.0.0.0.0.0 9.0 0 100 10 ppm (t1 HMBC ' ' ' dbf H H H Me H 1 3 α β Page 0
0.93 0.99 t Bu 1.7 9.3.0 1.0 alkane Page 1 3.1 3.31 3.31 3.310 3.30 3.99.9 3.9 3.930 3.91 3.90 3.900 3.79 3.3.09.090.00.0.0 3.9.9.1.179..3.1.790.7..10.0.0.90..17.03.39.3 Me CD 3 H 9 1 H MR (1) EtAc CD HD H H ' ' H ' H Me H 1 3 α β H' H-aliph. Fl. H' H H' B H' A CH α H β1 H β RC()CH Fl..13 3.0 0.9. 1.3.93 1.9.1 1.0.0.0 3.0.71.733 H 0.97 ppm (t1)
.0.33.0 7.133 7.109.97.9 7.193 7.1 7. 7.3 7.13 7.31 7.313 7.3 7.33 7.33 9 1 H MR () 1 3 β x H-m-Ph(Si) x H-p-Ph(Si) Me H H α ppm (t1) H H ' ' ' H x H-o-Ph(Me) x H-m -Fl H x H-m-Ph(Me) 0..00..3 0.0 7.11 7.73 7. 7. 7.1 7.37 9 7.3 7.379 7.3.00.073 7. 7.9 7.7 7.70 7.771 7.7 7.9 CHCl 3 x H-p 3 -Fl x H-o-Ph(Si) x H-o 1 -Fl x H-m -Fl 1..1.110.0.1 H H 3.3 Page
ppm (t1) 90 0 0 70 0 0 30 9.7.3 3.9 3.3..1.93.33 0.077 9.19 9.31.0.97.9 0.93.79 7.7 C 3 1 9 DEPT MR (1) Me C' C' H β Me α H H ' ' H H ' CD HD CH Fluorenyl CH α C CH β RC()CH Fluorenyl C' t Bu Page 3
ppm (t1) 10 10 110 130 10 13.03 11.9 113.79 13.9 13.7 13. 13.1 130.09 19.9 19.1 17.907 17.7 17. 1. 10.0 3 1 C 9 DEPT MR () H H β Me α H ' ' H H ' C x C-m-Ph(Si) x C-p 3 -Fl x C-o-Ph(Me) x C-o-Ph(Si) x C-m-Ph(Me) x C-m -Fl x C-p-Ph(Si) x C-m -Fl x C-o 1 -Fl Page
ppm (t1) 90 0 70 0 0 0 30 93.3.13.037 1.397 7.171.39 3.091.3.7.09 7.. 9.00 7.3 37.707.0 C RC()CH Fluorenyl C' C' C' Me CH α C 3 1 9 13 C MR (1) H H ' ' β Me α H H H ' CH Fluorenyl CD 3 D CH β t Bu Page
13.0 11.11 10.9 13.7 13.71 130.0 19.10 1.00 17.907 17.9 17. 17. 1.9 10.0 113.79 x C-m-Ph(Si) 3 1 9 13 C MR () H β α H H ' ' ' H Me H x C-o-Ph(Si) x C-m-Ph(Me) x C-p-Ph(Si) x C-p 3 -Fl x C-m -Fl x C-m -Fl C-p-Ph(Me) x C-o-Ph(Me) C x C-o 1 -Fl C 1.0 ppm (t1) 10.0 1.0 10.0 13.0 130.0 1.0 10.0 11.0 Page
ppm (t) 1.0.0 3.0.0.0.0.0 1.0.0 3.0.0.0.0.0 ppm (t1 9 CSY ' ' ' H H H H Me H 1 3 α β Page 7
0 3 1 9 HSQC 100 H β α H H ' ' ' H Me H 10 ppm (t1.0 ppm (t).0.0.0 3.0.0 1.0 Page
3.00.979.9.93.913.9. H β1 H β.10 3.00 Page 9 3.39 3.31 3.31 3.310 3.30 3.99 3.01 3.3 3.1 3.73 3.1 3. 3.7 Me CD HD CH 3 D H' A 1.09 3. 3.0 3.7 3.73 3.73 3.77.31.37.33 1 H MR (1) β Me H H.00 ppm (t1) α H' B CH α.3.00.39.31 H' 1.09.10.0.7.0.7.0.0. H' H 1.00 1.0 CD 3H H H ' ' ' H EtAc
.0.17 7.1 9.70.711.797.71 1 H MR () H H x H-m-Ph(Me) x H-o-Ph(Me) H H ' ' α β H ' H Me H H 1.0.00.13.1 ppm (t1).00 0.0.00 Page 0
ppm (t1) 10 100 0 13.31 1.33 131.71 11.99 0.907 9.01 1.3 79.3.0 7.73.3 9.333 C C x C-m-Ph(Me) x C-m-Ph(Me) DEPT MR H β α H H ' C' ' Me C C' ' H Me H CH α C CD HD CH β C' Page 1
ppm (t1) 90 0 70 0 0 0 9.00 1.0 79.3.0 7.7.37 9.1 9.391 9.1 9.00.1.709.39 0.90 C' C C' 13 C MR (1) H β α H ' ' H H ' Me H C' CH α Me C CD3D CH β Page
10.31 17.71 13.33 19.3 1.33 131.71 19.00 11. 11.00 13 C MR () C H H ' ' α β H C ' H Me H x C-m-Ph(Me) x C-o-Ph(Me) C-i-Ph(Me) C C C-p-Ph(Me) C 10 ppm (t1) 10 10 130 10 Page 3
H H ' ' α β H ' H Me H CSY.0 3.0.0.0.0.0 ppm (t1 ppm (t).0.0.0.0 3.0 Page
0 H H ' ' HSQC α β H ' H Me H 100 ppm (t1.0 ppm (t).0.0.0 3.0 Page
0 H H ' ' α β H ' H HMBC Me H 100 10 ppm (t1.0 ppm (t).0.0.0 3.0 Page
1.001 t Bu 9.3 1.0 Page 7 3.33.1.0.00.9. 3.0.9.909.97.99.93.99.0.0.9.9.1..017.007 3.990.1.09 7.70 7. 7.9 7. 7. 7.3 7.33 7. 7.7 7. 7.1 7.3 7. 7. 7.1 7.30 7.37 7.31 7.330.9.3 H 10 1 H MR H H x H-m-Ph x H-p-Ph TBDPS Br H ' x H-o-Ph ' ' H H H H H' A DMS H' B H' H H'.10 1.09 1.01 1.0 1.01 1.00 1.93..1 0.9 0.99.0.0.0.0 3.0.0 ppm (t1)
ppm (t1) 10 100 0 1.39 13.39 13.13 13.0 130.0 17.99 17.90. 79.93 79.7. 3.1.3 C x C-o-Ph x C-m-Ph x C-p-Ph C 10 DEPT MR TBDPS Br C C' C' ' ' C' ' H H C t Bu Page
ppm (t1) 10 100 0 1.0 1.39 19.71 13.37 13.13 13.03 13.1 13. 130.0 17.993 17.90 11.9. 79.9 79.. 3.1 0. 39.9 39.70 39.30 39.1 3.73 3.9. 1.00 C C C x C-m-Ph x C-o-Ph x C-p-Ph x C-i-Ph C C 10 13 C MR TBDPS Br ' ' C C' C' ' H C' H C DMS t Bu C- t Bu Page 9
10 CSY TBDPS ' ' Br ' H H 1.0.0 3.0.0.0.0.0 ppm (t1.0 ppm (t).0.0.0 3.0.0 1.0 Page 0
0 0 10 HSQC TBDPS ' ' Br ' H H 100 10 ppm (t1.0 ppm (t).0.0.0 3.0.0 1.0 Page 1