Electronic Supplementary Material (ESI) for RSC Advances. This journal is The Royal Society of Chemistry 205 Supporting Information An efficient one-pot decarboxylative aromatization of tetrahydro-β-carbolines by using - chlorosuccinimide: Total synthesis of norharmane, harmane and eudistomins Ahmed Kamal,* Manda Sathish, A. V. G. Prasanthi, Jadala Chetna, Yellaiah Tangella, Vunnam Srinivasulu, agula Shankaraiah and Abdullah Alarifi Contents Experimental section References page no S2-S9 S9 MR and 3 C MR spectrums S0-S45 S
Experimental Section General information Unless otherwise stated, all the starting materials and other reagents of the best grade were commercially available and were used without further purification. TLC was performed on 0.25 mm silica gel 60-F254 plates. Spots were visualized by UV light. All the melting points were taken by Electrothermal apparatus and the values are uncorrected. and 3 C MR spectra were recorded on 300 Mz, 400 Mz and 500 Mz MR instruments using tetramethylsilane as the internal standard. Chemical shifts are reported in parts per million (ppm) downfield from tetramethylsilane. Spin multiplicities are described as s (singlet), bs (broad singlet), d (doublet), dd (double doublet), t (triplet), q (quartet), or m (multiplet). Coupling constants are reported in hertz (z). RMS analyses were acquired on single quadruple and carried out using the ESI techniques at 70 ev. Wherever required column chromatography was performed using silica gel of 60 20 mm with hexane, ethyl acetate and methanol as eluents. Pictet-Spengler reaction and decarboxylative aromatization of L-tryptophan. 2 R Ac, 80 o C, h R a-t CS TEA, DMF rt, 30 min 2a-t R Scheme S: Synthesis of β-carboline (2a-t) unsing CS. General Procedure To a stirred solution of L-tryptophan (, mmol) in acetic acid was added aldehyde (. mmol), stirred at 80 o C for h and the acetic acid was removed under reduced pressure and dried well. This residue was taken in DMF, added TEA (3 mmol) and solution of CS (2. mmol) in DMF. Then the reaction mixture was stirred for 30 min at room temperature. After completion of the reaction (monitored by TLC), the reaction mixture was quenched with water, extracted with ethyl acetate and washed with saturated a 2 C 3 solution. The combined organic layers were washed with water, brine solution, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue obtained was purified by column chromatography by using ethyl acetate and hexane to afford the desired β-carbolines (2a-t). 9-Pyrido[3,4-b]indole (norharmane, 2a). Yellow solid: 80% yield; mp:95 98 C (ref. : (95 97 o C); MR (300 Mz, CDCl 3 ) δ: 9.6 (bs, ), 8.94 (s, ), 8.47 (d, J = 4.9 z, ), 8.4 (d, J = 7.9 z, ), 7.98 (d, J = 4.9 z, ), 7.58 7.5 (m, 2), 7.30 (t, J = 7.7 z, ); 3 C MR (25 Mz, DMS d 6 ) δ; 40.4, 37.9, 35.8, 33.9, 28.0, 27.3, 2.6, 20.5, 9., 4.5,.8; MS (ESI): m/z 69 [M + ] + ; RMS (ESI): calcd for C 9 2 m/z 69.0760 [M + ] + ; found: 69.0757. -Methyl-9-pyrido[3,4-b]indole (harmane, 2b). 2 ff white solid: 82% yield; mp: 230 233 C (ref. 2: 235 236 o C); MR (300 Mz, CDCl 3 + DMS d 6 ) δ: 0.77 (bs, ), 8.30 (d, J = 4.7 z, ), 8.0 (d, J = 7.5 z, ), 7.8 (d, J = 4.7 z, ), 7.63 7.48 (m, 2), 7.23 (t, J = 6.9 z, ), 2.86 (s, 3); 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) δ: 4.6, 40.2, 36.8, 34.3, 27.3, 26.9, 2.0, 20.7, 8.8, 2.,.5, 20.0; MS (ESI): m/z 83 [M + ] + ; RMS (ESI): calcd for C 2 2 m/z 83.096 [M + ] + ; found: 83.096. -Propyl-9-pyrido[3,4-b]indole (2c). 3 Brown colour solid: 78% yield; mp: 70 75 o C (ref. 3: 28 220 o C); MR (300 Mz, DMS d 6 ) δ:.05 (bs, ), 8.30 (d, J = 5.3 z, ), 8.09 (d, J = 7.7 z, ), 7.80 (d, J = 5.3 z, ), 7.58 (d, J = 8. z, ), 7.50 (t, J = 7.5 z, ), 7.22 (t, J = 7.5 z, ), 3.4 (t, J = 7.5 z, 2),.92 (q, J = 7.5, 5. z, 2),.05 (t, J = 7.2 z, 3); 3 C MR (00 Mz, DMS d 6 ) δ: 45.6, 40.2, 37.3, 34.0, 27.6, 26.9, 2.5, 20.9, 9.0, 2.4,.7, 35.3, 2.3, 3.8; MS (ESI): m/z 2 [M + ] + ; RMS (ESI): calcd for C 4 5 2 m/z 2.229 [M + ] + ; found: 2.26. -(4-Methoxybenzyl)-9-pyrido[3,4-b]indole (2d) S2
Yellow solid: 90% yield; mp: 42 44 C; MR (300 Mz, DMS d 6 ) δ:.67 (s, ), 8.26 (d, J = 5.3 z, ), 8.2 (d, J = 7.7 z, ), 7.96 (d, J = 5. z, ), 7.62 (d, J = 8. z, ), 7.54 (t, J = 7.2 z, ), 7.3 (d, J = 8.7 z, 2), 7.23 (t, J = 7.7 z, ), 6.82 (d, J = 8.5 z, 2), 4.38 (s, 2), 3.67 (s, 3); 3 C MR (00 Mz, DMS d 6 ) δ: 57.5, 44.7, 40.3, 37.6, 33.8, 3., 29.6, 27.9, 27.6, 2.6, 20.9, 9.2, 3.6, 2.8,.8, 54.8, 38.4; MS (ESI): m/z 289 [M + ] + ; RMS (ESI): calcd for C 9 7 2 m/z 289.335 [M + ] + ; found: 289.328. -Phenyl-9-pyrido[3,4-b]indole (2e). 2 245.074. Yellow solid: 85% yield; mp: 24 244 C (ref. 2: 24 242 o C); MR (300 Mz, DMS d 6 ) δ:.52 (bs, ), 8.47 (d, J = 5.2 z, ), 8.26 (d, J = 7.7 z, ), 8.3 (d, J = 5.3 z, ), 8.03 (d, J = 7.0 z, 2), 7.67 7.49 (m, 5), 7.26 (t, J = 7.5 z, ); 3 C MR (75 Mz, DMS d 6 ) δ: 42., 4.0, 38.3, 38.3, 32.9, 29.0, 28.6, 28.4, 28.3, 28.0, 2.5, 20.7, 9.4, 3.8, 2.3; MS (ESI): m/z 245 [M + ] + ; RMS (ESI): calcd for C 9 5 2 2 m/z 245.073 [M + ] + ; found: -(p-tolyl)-9-pyrido[3,4-b]indole (2f). 4 White solid: 88% yield; mp: 92 95 C (ref. 4: 90.3 9.6 o C); MR (300 Mz, CDCl 3 + DMS d 6 ) δ:.23 (bs, ), 8.38 (d, J = 5. z, ), 8. (d, J = 7.9 z, 2), 7.89 (t, J = 5.4 z, 3), 7.59 (d, J = 8.2 z, ), 7.45 (t, J = 7.3 z, ), 7.34 (d, J = 7.9 z, 2), 7.9 (t, J = 7.3 z, ), 2.4 (s, 3); 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) δ: 42.2, 40.8, 37.8, 37.5, 35.4, 32.8, 28.8, 27.9, 27.5, 20.8, 20.6, 8.9, 2.9, 2.0, 20.6; MS (ESI): m/z 259 [M + ] + ; RMS (ESI): calcd for C 8 5 2 m/z 259.229 [M + ] + ; found: 259.29. -(2-Methoxyphenyl)-9-pyrido[3,4-b]indole (2g). 5 White solid: 93% yield; mp: 57 60 C (ref. 5: 72 74 o C); MR (500 Mz, CDCl 3 ) δ: 8.58 (bs, ), 8.55 (d, J = 5.2 z, ), 8.7 (d, J = 7.9 z, ), 7.93 7.90 (m, 3), 7.55 (t, J = 7. z, ), 7.5 (t, J = 8. z, ), 7.32 (t, J = 7.6 z, ), 7. (d, J = 8.6 z, 2), 3.90 (s, 3); 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) δ: 58.7, 4.5, 40.2, 37.2, 32.2, 30., 28.7, 28.2, 26.8, 20., 8.3, 3.0,.9,.3, 54.2; MS (ESI): m/z 275 [M + ] + ; RMS (ESI): calcd for C 8 5 2 m/z 275.78 [M + ] + ; found: 275.66. -(3,4,5-Trimethoxyphenyl)-9-pyrido[3,4-b]indole (2h). 6 White solid: 92% yield; mp: 69 72 C (ref. 6: 67 69 o C); MR (500 Mz, CDCl 3 ) δ: 8.77 (bs, ), 8.55 (d, J = 5. z, ), 8.6 (d, J = 7.9 z, ), 7.94 (d, J = 5. z, ), 7.60 7.52 (m, 2), 7.33 (t, J = 7.5 z, ), 7.3 (s, ), 3.92 (s, 9); 3 C MR (CDCl 3, 75 Mz) δ: 53.5, 43.0, 40.5, 39.0, 38.2, 34.0, 33.4, 29.8, 28.4, 2.8, 2.7, 20., 3.7,.6, 05.2, 60.8, 56.; MS (ESI): m/z 335 [M + ] + ; RMS (ESI): calcd for C 9 5 2 2 m/z 335.390 [M + ] + ; found: 335.39. 2-Methoxy-4-(9-pyrido[3,4-b]indol--yl)phenol (2i). 7 White solid: 83% yield; mp: 262 264 C (ref. 7: 260 262 o C); MR (300 Mz, CDCl 3 + DMS d 6 ) δ:.7 (s, 0.8), 8.98 (s, 0.8), 8.35 (d, J = 5. z, ), 8.07 (d, J = 7.9 z, 2), 7.87 7.83 (m, ), 7.58 (d, J = 8. z, ), 7.5 (d, J =.7 z, 0.8), 7.46 7.40 (m, 2), 7.7 (d, J = 7.7 z, ), 6.98 (d, J = 8. z, ), 3.92 (s, 2.5), peaks at.29, 9.22, 7.54 and 3.96 are due to 20% minor rotamers; 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) δ: 47.4, 46.9, 42.5, 40.8, 37.6, 32.6, 29.5, 28.6, 27.4, 20.9, 20.7, 8.9, 5.2, 2.5, 2.,.8, 55.2; MS (ESI): m/z 29 [M + ] + ; RMS (ESI): calcd for C 8 5 2 2 m/z 29.28 [M + ] + ; found: 29.5. 3-(9-Pyrido[3,4-b]indol--yl)phenol (2j). 5 S3
Cream colour solid: 78% yield; mp: 23 26 C (ref. 5: 25 26 o C); MR (300 Mz, CDCl 3 + DMS d 6 ) δ: 0.79 (s, ), 9.4 (bs, ), 8.38 (d, J = 5. z, ), 7.85 (d, J = 7.7 z, ), 7.54 (d, J = 5. z, ), 7.6 (d, J = 3.0 z, ), 7.47 7.37 (m, 3), 7.30 (t, J = 7.7 z, ), 7.7 (t, J = 7.4 z, ), 6.87 (d, J = 7.2 z, ); 3 C MR (75 Mz, CDCl 3 + DMS d6) δ: 56.9, 42., 40.4, 39.0, 37.4, 32.6, 28.9, 28.6, 27., 20.4, 20.4, 8.6, 5.0, 4.8, 2.6,.5; MS (ESI): m/z 26 [M + ] + ; RMS (ESI): calcd for C 7 3 2 m/z 26.022 [M + ] + ; found: 26.09. -(4-Chlorophenyl)-9-pyrido[3,4-b]indole (2k). Light yellow solid: 80% yield; mp: 200 265 C; MR (300 Mz, CDCl 3 + DMS d 6 ) δ:.42 (s, ), 8.39 (d, J = 5.3 z, ), 8.3 (d, J = 7.7 z, ), 8.00 (s, ), 7.99 (d, J = 8.3 z, 2), 7.6 (d, J = 8.3 z, ), 7.55 (d, J = 8.5 z, 2), 7.48 (t, J = 7.2 z, ), 7.2 (t, J = 7.7 z, ); 3 C MR (25 Mz, CDCl 3 + DMS d6) δ: 4., 40.7, 37.8, 36.7, 33.4, 32.9, 29.8, 29.4, 28.4, 27.9, 2., 20.6, 9.3, 3.7, 2.; MS (ESI): m/z 279 [M + ] + ; RMS (ESI): calcd Cl for C 7 2 Cl 2 m/z 279.0689 [M + ] + ; found: 279.0942. -(4-Fluorophenyl)-9-pyrido[3,4-b]indole (2l). 4 White solid: 83% yield; mp: 206 209 C (ref. 4: 203 205 o C); MR (300 Mz, CDCl 3 + DMS d 6 ) δ:.03 (bs, ), 8.39 (d, J = 5.3 z, ), 8.06 (d, J = 7.7 z, ), 7.98 (q, J = 5.5, 8.5 z, 2), 7.87 (d, J = 5. z, ), 7.56 (d, J = 8. z, ),7.45 (t, J = 7.5 z, ), 7.25 7.4 (m, 3); 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) δ: 63.7 and 60.4 (d, J = 247.5 z), 4., 40.8, 37.8, 34.4, 32.8, 29.9 (d, J = 7.7 z), 289., 27.5, 20.7, 20.6, 9.0, 5.0 (d, J = 20.9 z), F 3.6,.8; MS (ESI): m/z 263 [M + ] + ; RMS (ESI): calcd for C 7 2 2 F m/z 263.0979 [M + ] + ; found: 263.0979. 4-(9-Pyrido[3,4-b]indol--yl)benzonitrile (2m). 5 White solid: 8% yield; mp: 230 233 C (ref. 5: 230 232 o C); MR (300 Mz, CDCl 3 + DMS d 6 ) δ:.03 (bs, ), C 8.45 (d, J = 5.3 z, ), 8.5 (d, J = 8. z, 2), 8.07 (d, J = 7.7 z, ), 7.93 (d, J = 5.3 z, ), 7.80 (d, J = 8. z, 2), 7.55 (d, J = 7.9 z, ), 7.47 (t, J = 5.5 z, ), 7.20 (t, J = 7.7 z, ); 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) δ: 42.6, 40.9, 39.6, 38.2, 33.2, 3.8, 29.8, 28.7, 27.9, 20.9, 20.6, 9.4, 8.3, 4.,.8, 0.9; MS (ESI): m/z 270 [M + ] + ; RMS (ESI): calcd for C 8 2 3 m/z 270.025 [M + ] + ; found: 270.026. -(4-itrophenyl)-9-pyrido[3,4-b]indole (2n). 5 Yellow solid: 79% yield; mp: 243 246 C (ref. 5: 244 246 C); MR (300 Mz, CDCl 3 + DMS d 6 ) δ: 0.82 (bs, ), 2 8.3 (d, J = 5.3 z, ), 8.7 (d, J = 8.9 z, 2), 8.06 (d, J = 8.9 z, 2), 7.92 (d, J = 7.9 z, ), 7.79 (d, J = 5. z, ), 7.40 (d, J = 8. z, ), 7.32 (t, J = 7.7 z, ), 7.06 (t, J = 7.0 z, ); 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) δ: 46.8, 44.5, 4.0, 39.2, 38.2, 33.3, 29.9, 29.0, 28.0, 23.2, 20.9, 20.5, 9.4, 4.4,.9; MS (ESI): m/z 290 [M + ] + ; RMS (ESI): calcd for C 7 2 2 3 m/z 290.0924 [M + ] + ; found: 290.0927. -(Benzo[d][,3]dioxol-5-yl)-9-pyrido[3,4-b]indole (2o). 2 White solid: 9% yield; mp: 69 73 C (Ref. 2: 7 72 C); MR (300 Mz, CDCl 3 + DMS d 6 ) δ:.06 (bs, ), 8.35 (d, J = 5. z, ), 8.06 (d, J = 7.9 z, ), 7.84 (d, J = 5. z, ), 7.57 (d, J = 8. z, ), 7.52 7.40 (m, 3), 7.7 (t, J = 7.2 z, ), 6.95 (d, J = 7.9 z, ), 6.02 (s, 2); 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) δ: 46.6, 46.5, 40.9, 40.0, 36.9, 3.8, 3.4, 28., 26.7, 2., 9.9, 9.8, 8.2, 2.0,., 07.6, 07., 99.9; MS (ESI): m/z 289 [M + ] + ; RMS (ESI): calcd for C 8 3 2 2 m/z 289.097 [M + ] + ; found: 289.0973. -(aphthalen--yl)-9-pyrido[3,4-b]indole (2p). 5 ff white solid: 94% yield; mp: 77 80 C (ref. 5: 78 80 C); MR (300 Mz, CDCl 3 + DMS d 6 ) δ: 0.80 (bs, ), 8.46 (d, J = 5.3 z, ), 8.2 (d, J = 7.9 z, ), 8.00 (d, J = 5.5 z, ), 7.95 (d, J = 5.5 z, ), 7.84 7.79 (m, S4
), 7.72 7.67 (m, 2), 7.62 (d, J = 7.5 z, ), 7.47 (t, J = 7.7 z, ), 7.45 7.40 (m, 2),7.34 (t, J = 8. z, ), 7.2 7.5 (m, ); 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) δ: 4.3, 39.7, 36.4, 34.3, 33.4, 32.3, 30.0, 27.4, 27.2, 26.7, 26.6, 26.0, 24.8, 24.5, 24.3, 24.0, 9.9, 9.5, 7.9, 2.3, 0.8; MS (ESI): m/z 295 [M + ] + ; RMS (ESI): calcd for C 2 4 2 m/z 295.229 [M+] + ; found: 295.232. -(Phenanthren-9-yl)-9-pyrido[3,4-b]indole (2q). ff white solid: 95% yield; mp: 230 235 C; MR (300 Mz, CDCl 3 + DMS d 6 ) δ:.5 (bs, ), 8.88 (t, J = 8.6 z, 2), 8.52 (d, J = 5.3 z, ), 8.22 (d, J = 7.9 z, ), 7.95 (d, J = 5.5 z, ), 8.3 (d, J = 5.3 z, ), 8.04 (s, ), 8.03 (d, J = 5.5 z, ), 7.78 7.64 (m, 4), 7.53 7.42 (m, 3), 7.26 7.9 (m, ); 3 C MR (25 Mz, CDCl 3 + DMS d 6 ) δ: 42.4, 40.9, 37.6, 37.5, 34.8, 33.8, 30.9, 30.3, 30.0, 28.9, 28.7, 28.2, 27.9, 27.2, 26.8, 26.6, 26.6, 26.3, 22.8, 22.4, 2.3, 20.7, 9.2, 3.8, 2.0; MS (ESI): m/z 345 [M + ] + ; RMS (ESI): calcd for C 25 7 2 m/z 345.386 [M + ] + ; found: 345.369. -(Pyridin-3-yl)-9-pyrido[3,4-b]indole (2r). 5 White solid: 9% yield; mp: 203 208 C (ref. 5: 205 208 C); MR (300 Mz, CDCl 3 + DMS d 6 ) δ:.08 (bs, ), 9.32 (s, ), 8.69 (dd, J =., 4.5 z, ), 8.55 (d, J = 5.2 z, ), 8.38 (d, J = 7.9 z, ), 8.6 (d, J = 7.9 z, ), 7.99 (d, J = 5. z, ), 7.63 (d, J = 8. z, ), 7.57 7.49 (m, 2), 7.28 (t, J = 7. z, ); 3 C MR (75 Mz, DMS d 6 ) δ: 49.3, 48.9, 4., 39.3, 38.5, 35.8, 34.0, 33.2, 29.3, 28.3, 23.8, 2.6, 20.6, 9.5, 4.4, 2.3; MS (ESI): m/z 246 [M + ] + ; RMS (ESI): calcd for C 6 2 3 m/z 246.025 [M + ] + ; found: 246.02. -(4-Fluoro-3-methoxyphenyl)-9-pyrido[3,4-b]indole (2s). F Creamish solid: 88% yield; mp: 30 35 C; MR (300 Mz, CDCl 3 + DMS d 6 ) δ:.45 (bs, ), 8.4 (d, J = 5. z, ), 8.7 (d, J = 6.7 z, ), 8.0 (d, J = 5. z, ), 7.7 (dd, J =.7, 8.5 z, ), 7.62 (d, J = 8.3 z, ), 7.59 7.53 (m, ), 7.50 (t, J = 7.9 z, ), 7.33 (dd, J = 8.3,. z, ), 7.22 (t, J = 7.2 z, ), 3.98 (s, 3); 3 C MR (25 Mz, CDCl 3 + DMS d 6 ) δ: 52.7 and 50.7 (d, J = 247.0 z), 47. (d, J = 0.9 z), 4.2, 4.0, 37.7 (d, J = 7.2 z), 34.8 (d, J = 2.7 z), 32.8, 29., 27.9, 27.8, 2., 20.6, 9.2, 5.6 (dd, J = 3.6, 7.2 z), 3.6, 3.5, 2.2, 55.7; MS (ESI): m/z 293 [M + ] + ; RMS (ESI): calcd for C 8 4 2 F m/z 293.084 [M + ] + ; found: 293.066. -(4-(trifluoromethyl)phenyl)-9-pyrido[3,4-b]indole (2t). CF 3 Light yellow solid: 85% yield; mp: 50 53 C; MR (400 Mz, DMS d 6 ) δ: 8.5 (d, J = 5. z, ), 8.30 (d, J = 7.9 z, ), 8.25 (d, J = 8. z, 2), 8.20 (d, J = 5.2 z, ), 7.97 (d, J = 8.2 z, 2), 7.65 (d, J = ), 7.58 (t, J = 5.8 z, ), 7.29 (t, J = 6.7 z, ); 3 C MR (25 Mz, DMS d 6 ) δ: 42.2, 4., 40.3, 38.4, 33., 29.5, 29., 28.7, 28.4, 28.3, 25.4, 2.6, 20.6, 9.6, 4.6, 2.3; MS (ESI): m/z 33 [M + ] +. Synthesis of Eudistomin I (6) -(Pyrrolidin-2-yl)-2,3,4,9-tetrahydro--pyrido[3,4-b]indole-3-carboxylic acid dihydrochloride (5) 2Cl A stirred solution of L-tryptophan (.0 g, 4.90 mmol) and -boc-l-prolinal (0.975 g, 4.90 mmol) in glacial acetic acid was heated at 80 o C for 2 h. After cooling to rt, the acetic acid was removed, the residue was taken in,4-dioxane (0 ml) and was added 2 Cl in,4-dioxane (5 ml) at 0 o C. The resulting reaction mixture was stirred at room temperature for 4 h. After total consumption of the starting material (monitored by TLC), the reaction mixture was concentrated under reduced pressure and dried well. The crude product was triturated in acetone, the resulted solid filtered and dried to afford the dihydrochloride salt 5 as white solid (.57 g, 90% yield). mp: 238 240 C; MR (300 Mz, DMS d 6 ) δ:.6 (s, 0.2),.47 (s, 0.8), 0.36 (bs, 0.3), 9.98 (bs, 0.8), 9.6 (bs, ), 7.53 (d, J = 7.9 z, ), 7.39 (d, J = 8. z, ), 7.6 (t, J = 7.3 z, ), 7.04 (t, J = 7. z, ), 5.44 5.24 (m, ), 4.74 4.63 (m, ), 4.6 4.5 (m, ), 4.30 4.5 (m, ), 3.46 3.27 (m, 3), S5
3.04 2.92 (m, ), 2.22.76 (m, 4); 3 C MR (75 Mz, DMS d 6 ) δ: 69.9, 36.5, 25.2, 25., 22.5, 9.2, 8.3,.6, 06.4, 59.2, 5.5, 5.2, 44.5, 27.5, 22.7, 22.; MS (ESI): m/z 286 [M + ] + ; RMS (ESI): calcd for C 6 20 2 3 m/z 286.550 [M + ] + ; found: 286.545. -(3,4-Dihydro-2-pyrrol-5-yl)-9-pyrido[3,4-b]indole (or) eudistomin I (6). 8 To a stirred solution of dihydrochloride salt 5 (500 mg,.39 mmol) in DMF (4 ml) was added TEA (0.97 ml, 6.98 mmol), cooled to 0 o C and added a solution of CS (0.575 mg, 4.32 mmol) in DMF (5 ml) and the reaction mixture was allowed to stir at room temperature 30 min. After the completion of starting material (monitored by TLC) reaction mixture was diluted with water and extracted with ethyl acetate (2x50 ml), washed with water (50 ml), brine (50 ml), dried over sodium sulfate and concentrated under reduced pressure. The crude product was purified by column chromatography using 20% ethyl acetate in `n-hexane to afford the eudistomin I (6, 288 mg, 70% yield) as a light yellow solid, mp: 5 54 C (ref. 8: 53 55 C); MR (500 Mz, CDCl 3 ) δ: 0.85 (s, ), 8.50 (d, J = 5.0 z, ), 8.5 (d, J = 7.9 z, ), 8.00 (d, J = 5. z, ), 7.6 7.53 (m, 2), 7.32 7.28 (m, ), 4.30 4.26 (m, 2), 3.37 3.3 (m, 2), 2.4 2.05 (m, 2); 3 C MR (25 Mz, CDCl 3 ) δ: 76.8, 40.8, 38.2, 35.8, 35.4, 29.5, 28.5, 2.8, 2.2, 20., 6.,.9, 62.2, 34.9, 2.9; MS (ESI): m/z 236 [M + ] +. RMS (ESI): calcd for C 5 4 3 m/z 236.82 [M + ] + ; found: 236.85. 6-Bromo-9-pyrido[3,4-b]indole (or) Eudistomin (7) 8 Br To a mixture of 0. 2 S 4 (.5 ml) and 37% formaldehyde (0.8 ml) was added L-tryptophane (0.5 g, 2.4 mmol) with stirring. After being stirred for 4 h at room temperature, the resulted white solid was collected by filtration and dried well. The solid material was taken in DMF (7 ml), added TEA (0.6 ml, 7.34 mmol), cooled to 0 o C and added solution of CS (0.69 g, 5.4 mmol) in DMF. The reaction mixture was stirred for 30 min at room temperature, diluted with water (50 ml), extracted with ethylacetate (2x50 ml) and washed with water (50 ml). The combined extracts were dried over sodium sulfate, filtered, concentrated in vacuo and the crude product was purified by silica gel column chromatography using ethyl acetate:n-hexane (:) to afford norharmane (2a, 0.33 g, 80% yield). To the stirred solution of 2a in acetic acid (0 ml) was added BS (0.38 g, 2.6 mmol) and stirred for 5 h at room temperature. The solvent most removed in vacuo and neutralized with saturated a 2 C 3 solution and extracted with ethylacetate (2x30 ml) and washed with water (30 ml). The combined extracts were dried over sodium sulfate, filtered, concentrated in vacuo and the crude product was purified by silica gel column chromatography using ethyl acetate:n-hexane (:) to afford eudistomin (7, 0.43 g, 89% yield) as creamish solid. Mp: 265 270 C (ref. 8: 265 268 o C); MR (300 Mz, CDCl 3 + DMS d 6 ) δ:.09 (bs, ), 8.84 (s, ), 8.3 (d, J = 5.3 z, ), 8.6 (S, ), 7.83 (d, J = 5. z, ), 7.5 (dd, J =.7, 8.6 z, ), 7.38 (d, J = 8.7 z, ); 3 C MR (25 Mz, CDCl 3 + DMS d 6 ) δ: 39., 37.6, 36.0, 33.7, 30.2, 26.8, 23.6, 22.2, 4.0, 3.,.3; MS (ESI): m/z 247 [M] + and 249 [M + 2] + ; RMS (ESI): calcd for C 8 2 Br m/z 246.9865 [M + ] + ; found: 246.9855. Synthesis of eudistomin T (9) tert-butyl 2-phenyl--(9-pyrido[3,4-b]indol--yl)ethylcarbamate (8) 9 Boc A stirred solution of L-tryptophan (.0 g, 4.90 mmol) and -boc-l-alaninal (.22 g, 4.90 mmol) in glacial acetic acid was heated at 80 o C for 2 h. After cooling to rt, the acetic acid was removed, the residue was taken DMF (7 ml), added TEA (2.0 ml, 4.70 mmol), cooled to 0 o C and added solution of CS (.37 g, 0.29 mmol) in DMF. The reaction mixture was stirred for 30 min at room temperature, diluted with water (70 ml), extracted with ethyl acetate (2x70 ml) and washed with water (00 ml). The combined extracts were dried over sodium sulfate, filtered, concentrated in vacuo and the crude product was purified by silica gel column chromatography using ethyl acetate:n-hexane (:) to afford compound 8 (.5 g, 80% yield) as white solid. Mp: 236 240 C (ref. 9: 230 232 o C); MR (400 Mz, DMS d 6 ) δ: 8.29 (d, J = 5. z, ), 8.2 (d, J = 7.8 z, ), 8.0 (d, J = 5. z, ), 7.62 (d, J = 8. z, ), 7.55 (t, J = 7.4 z, ), 7.32 7. (m, 7), 5.50 (q, J = 6.9, 3.8 z, 0.8), 3.2 3.09 (m, 2),.28 (s, 8), peaks at 5.32 and 0.99 are due to the 20% minor rotamer; 3 C MR (00 Mz, DMS d 6 ) δ: 55., 45., 40.3, 38., 37., 37.0, 32.6, 29.3, 27.9, 27.8, 27.7, 25.9, 2.6, 2.5, 20.7, 9.2, 3.5,.8, 77.8, 53., 28.0; MS (ESI): m/z 388 [M + ] + ; RMS (ESI): calcd for C 24 26 2 3 m/z 388.209 [M + ] + ; found: 388.2020. 2-Phenyl--(9-pyrido[3,4-b]indol--yl)ethanone (or) Eudistomin T (9) 9 S6
To a stirred solution of boc product 8 (0.3 g,.04 mmol) in,4-dioxane (20 ml) was added 2 Cl in,4-dioxane solution ( ml) at 0 o C and stirred for 3 h. After consumption of the starting material (monitored by TLC), the solvent removed in vacuo and dried. The crude product was dissolved in methanol (0 ml) and added sodium carbonate (4 g), followed by aq. acl ( ml, 5.9 % w/w) over a period of 5 mins. After being stirred for h at room temperature, reaction mixture was diluted with Cl solution (30 ml), extracted with DCM (2x30 ml), washed with saturated sodium bicarbonate solution (30 ml) and water (50 ml). The combined organic phases were dried over sodium sulfate, filtered and evaporated in vacuo. The crude product was purified by column chromatography using ethyl acetate and n-hexane (3:7) to afford eudistomin T (9) as yellow solid (0.9 g, 88% yield). Mp: 63 65 C (ref. 9: 55 57 o C); MR (400 Mz, CDCl 3 ) δ: 0.26 (bs, ), 8.59 (d, J = 4.9 z, ), 8.5 (d, J = 5.5 z, ), 8.4 (d, J = 8.9 z, ), 7.6 7.56 (m, ), 7.5 (d, J = 8.2 z, ), 7.43 7.40 (m, 2), 7.37 7.30 (m, 3), 7.29 7.24 (m, ), 4.74 (s, 2); 3 C MR (00 Mz, CDCl 3 ) δ: 202.3, 4.0, 38.2, 35.9, 35.3, 34.9, 3.6, 30.0, 29.2, 28.4, 26.7, 2.8, 20.7, 20.5, 9.2,.9, 43.9; MS (ESI): m/z 287 [M + ] + ; RMS (ESI): calcd for C 9 5 2 m/z 287.78 [M + ] + ; found: 287.75. Synthesis of -(-indol-3-yl)-9-pyrido[3,4-b]indole (or) Eudistomin U (0) 0 A stirred solution of L-tryptophan (0.50 g, 2.45 mmol) and indole-3-carbaldehyde (0.35 g, 2.45 mmol) in glacial acetic acid (5 ml) was heated at 80 o C for 2 h. After cooling to rt, the solvent most was removed in vacuo, the residue was taken DMF (5 ml), added TEA (.02 ml, 7.35 mmol), cooled to 0 o C and added solution of CS (0.69 g, 5.4 mmol) in DMF (5 ml). The reaction mixture was stirred for 30 min at room temperature, diluted with water (30 ml), extracted with ethyl acetate (2x50 ml) and washed with water (30 ml). The combined extracts were dried over sodium sulfate, filtered, evaporated in vacuo and the crude product was purified by silica gel column chromatography using ethyl acetate/methanol (9:) to afford eudistomin U (0, 0.59 g, 85% yield) as light yellow solid. Mp: 230 235 C (ref. 0: 235 236 C); MR (500 Mz, DMS d 6 ) δ:.72 (s, ),.3 (s, ), 8.55 (d, J = 7.9 z, ), 8.4 (d, J = 5. z, ), 8.30 (d, J = 2.7 z, ), 8.23 (d, J = 7.9 z, ), 7.95 (d, J = 5. z, ), 7.69 (d, J = 8. z, ), 7.56 7.50 (m, 2), 7.25 (t, J = 7.3 z, ), 7.2 (t, J = 7.0 z, ), 7.4 (t, J = 7.9 z, ); 3 C MR (00 Mz, DMS d 6 ) δ: 40.6, 40.3, 37.8, 36.4, 3.9, 28.0, 27.6, 26., 25.9, 22.2, 2.9, 2.3, 2., 9.7, 9.3, 3., 2.3,.5,.4; MS (ESI): m/z 284 [M + ] + ; RMS (ESI): calcd for C 9 4 3 m/z 284.82 [M + ] + ; found: 284.85. Pictet-Spengler reaction and aromatization of tetrahydro-β-carboline esters. 3 2 Cl R Et, 80 o C, 4h R 3a-h CS TEA, DMF rt, 30 min 4a-h R Scheme S2: Synthesis of methyl-β-carbolinecarboxylates (4a-h) General Procedure To a stirred solution of L-tryptophan methyl ester hydrochloride (3, mmol) in ethanol was added aldehyde ( mmol), stirred at 80 o C for 4 h and the ethanol was evaporated in vacuo and dried well. This residue was directly taken in DMF, added TEA (2.5 mmol) and CS (2. mmol) in DMF. Then the reaction mixture was stirred for 30 min at room temperature and after completion of the reaction (monitored by TLC), added ice cold water, the resulted solid was filtered, washed with water and dried well. The solid product was then triturated in 20-50% ethyl acetate and hexane solvent system, filtered and dried to afford the pure desired β-carboline esters (4a-h). Methyl -phenethyl-9-pyrido[3,4-b]indole-3-carboxylate (4a). Brown solid: 8% yield; mp: 65 70 o C; MR (300 Mz, CDCl 3 ) δ: 8.77 (s, ), 8.30 (bs, ), 8.3 (d, J = 7.9 z, ), 7.52 (t, J = 8.2 z, ), 7.37 (d, J = 8.2 z, ), 7.30 (t, J = 7. z, ), 7.2 7.5 (m, 3), 7.2 (d, J = 7.9 z, 2), 4.05 (s, 3), 3.47 (t, J = 7.3 z, 2), 3.8 (t, J = 7.7 z, 2); 3 C MR (00 Mz, DMS d 6 ) δ: 66., 44.8, 4.5, 40.6, 35.9, 35.6, 28.4, 28.3, 28., 27., 25.8, 2.9, 2.2, 20.6, 6.0, 2.2, 5.8, 35., 33.5; MS (ESI): m/z 33 [M + ] + ; RMS (ESI): calcd for C 2 9 2 2 m/z 33.44 [M + ] + ; found: 33.428. Methyl -(3,4,5-trimethoxyphenyl)-9-pyrido[3,4-b]indole-3-carboxylate (4b). S7
ff white solid: 94% yield; mp: 226 229 C (ref. : 229 230 o C); MR (300 Mz, CDCl 3 + DMS d 6 ) δ: 8.79 (s, ), 8.22 (d, J = 7.9 z, ), 7.64 (d, J = 8.3 z, ), 7.5 (t, J = 7.2 z, ), 7.26 (t, J = 7.2 z, ), 7.7 (s, 2), 3.93 (s, 3), 3.92 (s, 6), 3.79 (s, 3); 3 C MR (CDCl 3, 75 Mz) δ: 65.8, 52.7, 42.2, 4.2, 37.8, 36.2, 34.5, 32.9, 28.7, 28.0, 2., 20.9, 9.9, 6., 2.4, 05.5, 59.9, 55.5, 5.6; MS (ESI): m/z 393 [M + ] + ; RMS (ESI): calcd for C 22 2 5 2 m/z 393.445 [M + ] + ; found: 393.432. Methyl -(naphthalen--yl)-9-pyrido[3,4-b]indole-3-carboxylate (4c). White solid: 95% yield; mp: 294 297 C; MR (300 Mz, DMS d 6 ) δ:.6 (s, ), 9.05 (s, ), 8.48 (d, J = 7.7 z, ), 8.6 (dd, J = 2.5, 6.8 z, ), 8. (d, J = 8. z, ), 7.78 7.73 (m, 2), 7.62 7.53 (m, 4), 7.44 (t, J = 6.9 z, ), 7.33 (t, J = 7.7 z, ), 3.90 (s, 3): 3 C MR (25 Mz, DMS d 6 ) δ: 66.0, 42.4, 4.2, 36.3, 36.2, 34.6, 33.4, 3., 28.9, 28.6, 28.4, 28.2, 27.5, 26.5, 26., 25.5, 25.2, 22., 2., 20.2, 6.9, 2.5, 5.9; MS (ESI): m/z 353 [M + ] + ; RMS (ESI): calcd for C 23 7 2 2 m/z 353.284 [M + ]+; found: 353.288. Methyl -(4-chlorophenyl)-9-pyrido[3,4-b]indole-3-carboxylate (4d). 2 Yellow solid: 92% yield; mp: 268 272 o C (ref. 2: 270 o C); MR (300 Mz, CDCl 3 + DMS d 6 ) δ (ppm): 8.8 (s, ), 8.23 (d, J = 7.7 z, ), 8.0 (d, J = 8.3 z, ), 7.64 (d, J = 8.3 z, ), 7.59 7.5 (m, 3), 7.27 (t, J = 7.2 z, ), 6.92 (d, J = 7.4 z, ), 3.93 (s, 3); 3 C MR (00 Mz, DMS d 6 ) δ (ppm); 65.8, 4.4, 40.6, 36.5, 36.2, 34.4, 33.6, 30.3, 29.3, 28.7, 25.4, 2.9, 20.9, 20.4, 6.8, 2.6, 5.9; MS (ESI): m/z 337 [M + ] + ; RMS (ESI): calcd for C 9 4 2 2 Cl m/z 337.0738 [M + ] + ; found: 337.0729. Cl Methyl -(phenanthren-9-yl)-9-pyrido[3,4-b]indole-3-carboxylate (4e). 9 White solid: 96% yield; mp: 290 295 C; MR (300 Mz, DMS d 6 + CDCl 3 ) δ:.56 (s, ), 8.98 (s, ), 8.89 (t, J = 8.7 z, 2), 8.34 (d, J = 7.9 z, ), 8.03 (d, J = 6.6 z, 2), 7.80 7.60 (m, 4), 7.52 7.45 (m, 3), 7.29 (t, J = 7.9 z, ), 3.92 (s, 3): 3 C MR (25 Mz, DMS d 6 + CDCl 3 ) δ: 65.9, 42.3, 4.2, 36.4, 36.2, 33.2, 30.8, 30.2, 30., 30.0, 28.9, 28.4, 28.3, 27.2, 26.8, 26.7, 26.6, 26., 22.8, 22.5, 2.5, 2.0, 20.0, 6.8, 2.3, 5.8; MS (ESI): m/z 403 [M + ] + ; RMS (ESI): calcd for C 27 9 2 2 m/z 403.44 [M + ]+; found: 403.427. Methyl -(4-fluoro-3-methoxyphenyl)-9-pyrido[3,4-b]indole-3-carboxylate (4f). ff white solid: 94% yield; mp: 25 220 o C; MR (300 Mz, DMS d 6 ) δ: 8.94 (s, ), 8.44 (d, J = 7.9 z, ), 7.73 7.66 (m, 2), 7.6 (t, J = 7.2 z, ), 7.55 7.43 (m, 2), 7.34 (t, J = 7.4 z, ), 3.99 (s, 3), 3.93 (s, 3); 3 C MR (725 Mz, DMS d 6 ) δ: 65.8, 52.8 and 50.9 (d, J = 246. z), 47. (d, J = 0.9 z), 4.3 (d, J = 3.6 z),, 36.4, 34.5, 34.2 (d, J = 3.6 z), 29.0, 28.6, 2.9, 2. (d, J = 7.2 z), 2.0, 20.3, 6.7, 6., F 6.0, 4.0 (.8 z), 2.6, 55.9, 5.9; MS (ESI): m/z 35 [M + ] + ; RMS (ESI): calcd for C 20 6 3 2 F m/z 35.39 [M + ] + ; found: 35.28. Methyl -(4-(trifluoromethyl)phenyl)-9-pyrido[3,4-b]indole-3-carboxylate (4g). 5 White solid: 9% yield; mp: 303 306 C (ref. 5: 306 30 o C); MR (300 Mz, DMS d 6 ) δ: 8.80 (s, ), 8.3 (t, J = 7.4 z, 3), 7.75 (d, J = 8.3 z, 2), 7.60 (d, J = 8. z, ), 7.50 (t, J = 7.7 z, ), 7.26 (t, J = 7.5 z, ), 3.95 (s, 3); 3 C MR (75 Mz, DMS d 6 ) δ: 65.6, 4.4, 4.2, 40.2, 36.6, 34.6, 29.4,, 29.3, 29.2, 29.2, 28.5, 25.3 (q, J = 3.8, 7.7 z), 2.7, 20.9, 20.3, 6.9, 2.5, 5.8; MS (ESI): m/z 37 [M + ] + ; RMS (ESI): calcd for C 20 4 2 2 F 3 m/z 37.00 [M + ] + ; found: 37.0993. CF 3 Methyl -(-((tert-butoxycarbonyl)amino)-2-phenylethyl)-9-pyrido[3,4-b]indole-3-carboxylate (4h) S8
White solid: 88% yield; mp: 47 50 C; MR (400 Mz, DMS d 6 ) δ: 2.0 (bs, ), 8.85 (s, ), 8.38 (d, J = Boc 7.8 z, ), 7.69 (d, J = 8.2 z, ), 7.62 (t, J = 7.2 z, ), 7.37 7.26 (m, 4), 7.22 (t, J = 7.2 z, 2), 7.4 (d, J = 7.2 z, ), 5.52 (q, J = 7.2, 4.7 z, ), 3.94 (s, 3), 3.22 (d, J = 7. z, 2),.30 and 0.96 (s, 8 and s, ); 3 C MR (00 Mz, DMS d 6 ) δ: 65.8, 55., 45.2, 40.7, 37.9, 35.7, 34.5, 29.4, 28.5, 27.9, 27.7, 26.0, 2.9, 20.9, 20.2, 6.7, 2.2, 78.0, 53.6, 5.9, 40.0, 28.0; MS (ESI): m/z 446 [M + ] + ; RMS (ESI): calcd for C 26 28 4 3 m/z 446.2074 [M + ] + ; found: 446.2063. -(4-Methoxyphenyl)-4,9-dihydro-3-pyrido[3,4-b]indole (4). 3 Creamish solid: 85% yield; mp: 85 88 C (ref. 3: 96 97 C); MR (300 Mz, DMS d 6 ) δ: 7.78 (d, J = 7.6 z, ), 7.46 7.39 (m, ), 7.34 7.28 (m, 2), 6.76 (d, J = 8.8 z, 2), 6.29 (d, J = 8.8 z, 2), 4.67 4.55 (m, ), 4.5 4.39 (m, ), 3.52 (s, 3), 2.94 (m, ), 2.3 2.2 (m, ); 3 C MR (75 Mz, DMS d 6 ) δ: 74., 67.5, 60., 53.5, 43.8, 28.6, 28.5, 27.7, 25.3, 22.6, 2.9, 3., 72.5, 59.8, 54.6, 36.9; MS (ESI): m/z 277 [M + ] +. -(4-itrophenyl)-4,9-dihydro-3-pyrido[3,4-b]indole (5) 4 2 Yellow solid: 82% yield; mp: 28 220 C (ref. 4: 220 222 C); MR (300 Mz, DMS d 6 + CDCl 3 ) δ:.04 (s, ), 8.30 (d, J = 8.7 z, 2), 7.99 (d, J = 8.7 z, 2), 7.55 (d, J = 7.9 z, ), 7.38 (d, J = 8. z, ), 7.7 (t, J = 7.5 z, ), 7.04 (t, J = 7.5 z, ), 3.96 (t, J = 7.9 z, 2), 2.89 (t, J = 8.3 z, 2); 3 C MR (75 Mz, DMS d 6 + CDCl 3 ) δ: 55.8, 46.4, 4.6, 35.5, 27.6, 25.3, 23.0, 22.3, 2.6, 8.0, 7.8, 5.3, 0.9, 47., 7.3; MS (ESI): m/z 292 [M + ] +. References. T.. Trieu, J. Dong, Q. Zhang, B. Zheng, T. Z. Meng, X. Lu and X. X. Shi, Eur. J. rg. Chem., 203, 6, 327. 2. J. Dong, X. X. Shi, J. J. Yan, J. Xing, Q. Zhang and S. Xiao, Eur. J. rg. Chem., 200, 36, 6987. 3. Y. iroshi, K. Kazuo and. Tamotsu, eterocycles, 999, 5, 28. 4. A. Kulkarni, M. Abid, B. Toeroek and X. uang, Tetrahedron Lett., 2009, 50, 79. 5. A. Kamal, Y. Tangella, K. L. Manasa, M. Sathish, V. Srinivasulu, J. Chetna and A. Alarifi, rg. Biomol. Chem., 205, 3, 8652. 6. W. Qifeng, C. Rihui, F. Manxiu, G. Xiangdong, M. Chunming, L. Jinbing, S. uacan and P. Wenlie, Eur. J. Med. Chem., 2009, 44, 533. 7. S. Li, B. Yang, Q. Zhang, J. Zhang, J. Wang and W. Wu, at. Prod. Commun., 200, 5, 59. 8. K. L. Rinehart, Jr., J. Kobayashi, G. C. arbour, J. Gilmore, M. Mascal, T. G. olt, L. S. Shield and F. Lafargue, J. Am. Chem. Soc., 987, 09, 3378. 9. J. Mculty and I. W. J. Still, J. Chem. Soc. Perkin Trans,. 994,, 329; 0. F. issen, V. Richard, C. Alayrac and B. Witulski, Chem. Commun., 20, 47, 6656.. A. Kamal, V. Srinivasulu, V. L. ayak, M. Sathish, C. Bagul,. V. S. Reddy,. Shankaraiah,. Rangaraj and. agesh, ChemMedChem, 204, 9, 2084. 2. S. K. Srivastava, A. Agarwal, P. M. S. Chauhan, S. K. Agarwal, A. P. Bhaduri, S.. Singh,. Fatima and R. K. Chatterjee, Bioorg. Med. Chem., 999, 7, 223. 3. A. E. and S. S. Stahl, J. Am. Chem. Soc., 204, 36, 506. 4. B. Pal, P. and G. S. Venkatachalam, Syn. Comm., 2003, 33, 2339. S9
9-Pyrido[3,4-b]indole (norharmane, 2a) MR (300 Mz, CDCl 3 ) orharmane (2a) 3 C MR (25 Mz, DMS d 6 ) orharmane (2a) S0
-Methyl-9-pyrido[3,4-b]indole (harmane, 2b) MR (300 Mz, CDCl 3 + DMS d 6 ) armane (2b) 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) armane (2b) S
-Propyl-9-pyrido[3,4-b]indole (2c) MR (300 Mz, DMS d 6 ) 2c 3 C MR (00 Mz, DMS d 6 ) 2c S2
-(4-Methoxybenzyl)-9-pyrido[3,4-b]indole (2d) MR (300 Mz, DMS d 6 ) 2d 3 C MR (00 Mz, DMS d 6 ) 2d S3
-Phenyl-9-pyrido[3,4-b]indole (2e) MR (300 Mz, DMS d 6 ) 2e 3 C MR (75 Mz, DMS d 6 ) 2e S4
-(p-tolyl)-9-pyrido[3,4-b]indole (2f) MR (300 Mz, CDCl 3 + DMS d 6 ) 2f 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) 2f S5
-(2-Methoxyphenyl)-9-pyrido[3,4-b]indole (2g) MR (500 Mz, CDCl 3 ) 2g 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) 2g S6
-(3,4,5-Trimethoxyphenyl)-9-pyrido[3,4-b]indole (2h) MR (500 Mz, CDCl 3 ) 2h 3 C MR (CDCl 3, 75 Mz) 2h S7
2-Methoxy-4-(9-pyrido[3,4-b]indol--yl)phenol (2i) MR (300 Mz, CDCl 3 + DMS d 6 ) 2i 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) 2i S8
3-(9-Pyrido[3,4-b]indol--yl)phenol (2j) MR (300 Mz, CDCl 3 + DMS d 6 ) 2j 3 C MR (75 Mz, CDCl 3 + DMS d6) 2j S9
-(4-Chlorophenyl)-9-pyrido[3,4-b]indole (2k) MR (300 Mz, CDCl 3 + DMS d 6 ) 2k Cl 3 C MR (25 Mz, CDCl 3 + DMS d6) 2k Cl S20
-(4-Fluorophenyl)-9-pyrido[3,4-b]indole (2l) MR (300 Mz, CDCl 3 + DMS d 6 ) 2l F 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) 2l F S2
4-(9-Pyrido[3,4-b]indol--yl)benzonitrile (2m) MR (300 Mz, CDCl 3 + DMS d 6 ) 2m C 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) 2m C S22
-(4-itrophenyl)-9-pyrido[3,4-b]indole (2n) MR (300 Mz, CDCl 3 + DMS d 6 ) 2n 2 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) 2n 2 S23
-(Benzo[d][,3]dioxol-5-yl)-9-pyrido[3,4-b]indole (2o) MR (300 Mz, CDCl 3 + DMS d 6 ) 2o 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) 2o S24
-(aphthalen--yl)-9-pyrido[3,4-b]indole (2p) MR (300 Mz, CDCl 3 + DMS d 6 ) 2p 3 C MR (75 Mz, CDCl 3 + DMS d 6 ) 2p S25
-(Phenanthren-9-yl)-9-pyrido[3,4-b]indole (2q) MR (300 Mz, CDCl 3 + DMS d 6 ) 2q 3 C MR (25 Mz, CDCl 3 + DMS d 6 ) 2q S26
-(Pyridin-3-yl)-9-pyrido[3,4-b]indole (2r) MR (300 Mz, CDCl 3 + DMS d 6 ) 2r 3 C MR (75 Mz, DMS d 6 ) 2r S27
-(4-Fluoro-3-methoxyphenyl)-9-pyrido[3,4-b]indole (2s) MR (300 Mz, CDCl 3 + DMS d 6 ) 2s F 3 C MR (25 Mz, CDCl 3 + DMS d 6 ) 2s F S28
-(4-(trifluoromethyl)phenyl)-9-pyrido[3,4-b]indole (2t) MR (400 Mz, DMS d 6 ) 2t CF 3 3 C MR (25 Mz, DMS d 6 ) 2t CF 3 S29
-(Pyrrolidin-2-yl)-2,3,4,9-tetrahydro--pyrido[3,4-b]indole-3-carboxylic acid dihydrochloride (5) MR (300 Mz, DMS d 6 ) 5 2Cl 3 C MR (75 Mz, DMS d 6 ) 5 2Cl S30
-(3,4-Dihydro-2-pyrrol-5-yl)-9-pyrido[3,4-b]indole (or) eudistomin I (6) MR (500 Mz, CDCl 3 ) eudistomin I, (6) 3 C MR (25 Mz, CDCl 3 ) eudistomin I, (6) S3
6-Bromo-9-pyrido[3,4-b]indole (or) Eudistomin (7) MR (300 Mz, CDCl 3 + DMS d 6 ) Br eudistomin (7) 3 C MR (25 Mz, CDCl 3 + DMS d 6 ) Br eudistomin (7) S32
tert-butyl 2-phenyl--(9-pyrido[3,4-b]indol--yl)ethylcarbamate (8) MR (400 Mz, DMS d 6 ) Boc 8 3 C MR (00 Mz, DMS d 6 ) Boc 8 S33
2-Phenyl--(9-pyrido[3,4-b]indol--yl)ethanone (or) Eudistomin T (9) MR (400 Mz, CDCl 3 ) eudistomin T (9) 3 C MR (00 Mz, CDCl 3 ) eudistomin T (9) S34
Synthesis of -(-indol-3-yl)-9-pyrido[3,4-b]indole (or) Eudistomin U (0) MR (500 Mz, DMS d 6 ) eudistomin U (0) 3 C MR (00 Mz, DMS d 6 ) eudistomin U (0) S35
Methyl -phenethyl-9-pyrido[3,4-b]indole-3-carboxylate (4a) MR (300 Mz, CDCl 3 ) 4a 3 C MR (00 Mz, DMS d 6 ) 4a S36
Methyl -(3,4,5-trimethoxyphenyl)-9-pyrido[3,4-b]indole-3-carboxylate (4b) MR (300 Mz, CDCl 3 + DMS d 6 ) 4b 3 C MR (CDCl 3, 75 Mz) 4b S37
Methyl -(naphthalen--yl)-9-pyrido[3,4-b]indole-3-carboxylate (4c) MR (300 Mz, DMS d 6 ) 4c 3 C MR (25 Mz, DMS d 6 ) 4c S38
Methyl -(4-chlorophenyl)-9-pyrido[3,4-b]indole-3-carboxylate (4d) MR (300 Mz, CDCl 3 + DMS d 6 ) 4d Cl 3 C MR (00 Mz, DMS d 6 ) Cl 4d S39
Methyl -(phenanthren-9-yl)-9-pyrido[3,4-b]indole-3-carboxylate (4e) MR (300 Mz, DMS d 6 + CDCl 3 ) 4e 3 C MR (25 Mz, DMS d 6 + CDCl 3 ) 4e S40
Methyl -(4-fluoro-3-methoxyphenyl)-9-pyrido[3,4-b]indole-3-carboxylate (4f) MR (300 Mz, DMS d 6 ) F 4f 3 C MR (725 Mz, DMS d 6 ) F 4f S4
Methyl -(4-(trifluoromethyl)phenyl)-9-pyrido[3,4-b]indole-3-carboxylate (4g) MR (300 Mz, DMS d 6 ) 4g CF 3 3 C MR (75 Mz, DMS d 6 ) 4g CF 3 S42
Methyl -(-((tert-butoxycarbonyl)amino)-2-phenylethyl)-9-pyrido[3,4-b]indole-3-carboxylate (4h) MR (400 Mz, DMS d 6 ) Boc 4h 3 C MR (00 Mz, DMS d 6 ) Boc 4h S43
-(4-Methoxyphenyl)-4,9-dihydro-3-pyrido[3,4-b]indole (5) MR (300 Mz, DMS d 6 ) 5 3 C MR (75 Mz, DMS d 6 ) 5 S44
-(4-itrophenyl)-4,9-dihydro-3-pyrido[3,4-b]indole (6) MR (300 Mz, DMS d 6 + CDCl 3 ) 6 2 3 C MR (75 Mz, DMS d 6 + CDCl 3 ) 6 2 S45