An Unusual Diastereoselective Pictet–Spengler Reaction: Synthesis of Novel Tetrahydro-β-Carboline Glycosides

Abstract

An unusual kinetic approach to the Pictet–Spengler reaction was investigated, in which l- or d-tryptophan methyl ester ­reacted with aldehydes of 1,2-O-cyclohexylidene-3-allyloxy-α-d-xylofuranose, yielding exclusively the cis or trans diastereomer of tetrahydro-β-carboline glycoside, respectively, with complete ­stereocontrol.

Keywords

Pictet–Spengler reaction - stereoselectivity - diastereoselectivity - stereocontrol - glycosides - imines - π-stacking interactions

• References and Notes

• 1 Corresponding author’s current address: Senior Scientist, TCGLS, BN 7, Sector V, Saltlake, Kolkata, 700091, India
• 2 Pictet A, Spengler T. Ber. Dtsch. Chem. Ges. 1911; 44: 2030
• 3 Inorganic reactions . Vol. 6. Whaly WM, Govindachari TR, Adams R. John Wiley & Sons; New York: 1951: 151
• 4a Natarajan S, Ganeshan A. Chem. Commun. 2003; 916
• 4b Yamada H, Kawate T, Matsunigu M, Nishuda A, Yamaguchi K, Nakagawa M. J. Org. Chem. 1998; 63: 6348
• 4c Nikamura S, Tanaka M, Taniguchi T, Uchayama M, Ohwada T. Org. Lett. 2003; 5: 2087
• 5 Jaisankar P, Pal B, Giri VS. Synth. Commun. 2003; 33: 2339
• 6a Soerens D, Sandrin J, Unggemuch F, Mokry P, Wu GS, Yamanaka E, Hutchins L, Dipierro M, Cook JM. J. Org. Chem. 1979; 44: 535
• 6b Cox ED, Cook JM. Chem. Rev. 1995; 95: 1797
• 7a Larghi EL, Marcola A, Bracca AB. J, Kaufman TS. ARKIVOC 2005; (xii): 98
• 7b Pulka K, Kulis P, Tymecka D, Frankiewicz L, Wilczek M, Kozminski W, Misicka A. Tetrahedron 2008; 64: 1506
• 8 Manna RK, Jaisankar P, Giri VS. Synth. Commun. 1995; 25: 3027
• 9 Zhao P, Jin H.-W, Yang Z.-J, Zhang L.-R, Zhang L.-H. Org. Biomol. Chem. 2008; 6: 3741
• 10a Sandrin J, Soerens D, Cook JM. Heterocycles 1976; 4: 1249
• 10b Sandrin J, Soerens D, Hutchins L, Richfield E, Ungemach F, Cook JM. Heterocycles 1973; 4: 1101
• 10c Levy GC, Lichter RL, Nelson GL. Carbon-13 Nuclear Magnetic Resonance Spectroscopy. 2^nd ed Wiley Interscience; New York: 1980: 55
• 11 Giri VS, Mukherjee R, Burman AC, Gurjar MK, Yadav JS, Jaggi M, Singh AT, Srivastava SK, Jaisankar P, Pal B, Banerjee AK, Wakharkar RD. PCT Int. Appl. WO 2005/121143 A1, 2005 ; Chem. Abstr. 2005: 1330326.
• 12 Furniss BS, Hannaford AJ, Smith PW. G, Tatchell AR. Vogel’s Text Book of Practical Organic Chemistry . Longman Group UK Ltd; England: 1989. 5^th ed. 657
• 13 Preparation of Compounds 3–28; General Procedure: To a stirred solution of free tryptamine (1a; 2 mmol) or l-tryptophan methyl ester (1b; 2 mmol) or d-tryptophan methyl ester (1c; 2 mmol), sugar aldehyde 2a–d (2 mmol) and activated 4 Å molecular sieves (10 mg/mmol) in CH₂Cl₂ (20 mL), TFA (0.2 mL) was added. The reaction mixture was stirred at room temperature for 4–6 h and the progress was monitored by TLC (CHCl₃–MeOH, 9:1). Upon completion of the reaction, solvent was removed and the crude material was either directly used for column purification or diluted with H₂O, extracted with CH₂Cl₂ (3 × 25 mL), washed with very dilute aq HCl (10 mL), sat. NaHCO₃ (10 mL), H₂O (20 mL), and brine (20 mL) and dried over anhydrous Na₂SO₄ and the solvent was evaporated. The residue was purified by silica-gel column chromatography (petroleum ether–CHCl₃–MeOH).10,11-O-Cyclohexylidene-12β-hydroxy-(1-tetrahydro-β-carbonlinyl)tetrahydrofuran (3a) and its conformer (3b): The residue was purified by chromatography over silica gel using CHCl₃ to afford 3a (518 mg, 70%) and CHCl₃–MeOH (99:1) to afford 3b (188.2 mg, 25%).Compound 3a: mp 200–202 °C; [α]_D –54.0 (c 0.48, CHCl₃). IR (KBr): 3454, 3088, 1034, 735 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.50 (br s, 1 H, NH), 7.49 (d, J = 7.6 Hz, 1 H), 7.34 (d, J = 7.9 Hz, 1 H), 7.07–7.21 (m, 2 H), 6.08 (d, J = 3.6 Hz, 1 H), 4.53–4.60 (m, 2 H), 4.37–4.41 (m, 1 H), 4.26 (br s, 1 H), 3.33–3.38 (m, 1 H), 2.96–2.99 (m, 2 H), 2.77–2.85 (m, 2 H), 1.40–1.75 (m, 11 H). ¹³C NMR (75 MHz, CDCl₃): δ = 136.0, 131.6, 127.0, 121.8, 119.4, 118.1, 112.5, 111.0, 109.5, 104.9, 85.0, 81.5, 75.6, 52.9, 42.9, 36.4, 35.5, 24.8, 23.9, 23.5, 22.1. MS (ESI): m/z = 371 [M + H]⁺. Anal. Calcd for C₂₁H₂₆N₂O₄: C, 68.09; H, 7.07; N, 7.56. Found: C, 67.81; H, 7.37; N, 7.91.Compound 3b: mp 235–237 °C; [α]_D –19.7 (c 0.58, CHCl₃). IR (KBr): 3454, 2936, 1448, 1120, 1016, 734 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.20 (br s, 1 H, NH), 7.47 (d, J = 7.3 Hz, 1 H), 7.07–7.26 (m, 3 H), 5.98 (d, J = 3.5 Hz, 1 H), 4.49–4.54 (m, 2 H), 4.38 (d, J = 2.5 Hz, 2 H), 3.34–3.43 (m, 1 H), 3.00–3.10 (m, 1 H), 2.64–2.81 (m, 2 H), 1.41–1.74 (m, 11 H). ¹³C NMR (75 MHz, CDCl₃): δ = 136.3, 131.8, 127.7, 122.3, 119.8, 118.5, 112.7, 111.4, 110.6, 105.0, 85.5, 79.3, 77.8, 52.7, 41.9, 37.0, 35.9, 25.2, 24.3, 23.9, 22.3. MS (ESI): m/z = 371 [M + H]⁺. Anal. Calcd for C₂₁H₂₆N₂O₄: C, 68.09; H, 7.07; N, 7.56. Found: C, 67.78; H, 7.27; N, 7.51.10,11-O-Cyclohexylidene-12β-hydroxy(1-tetrahydro-3β-carbomethoxycarbolinyl)tetrahydrofuran (4a) and its isomer (4b): The residue was purified by chromatography over silica gel using CHCl₃–petroleum ether (95:5) to afford 4a (643 mg, 75%) and the CHCl₃ eluent to afford 4b (180 mg, 21%).Compound 4a: mp 90–92 °C; [α]_D –50.90 (c 0.5, CHCl₃). IR (KBr): 3328, 2937, 1740, 1448, 1072, 753 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.43 (s, 1 H, NH), 7.52 (d, J = 7.7 Hz, 1 H), 7.39 (d, J = 7.9 Hz, 1 H), 7.22 (t, J = 7.9 Hz, 1 H), 7.14 (t, J = 7.5 Hz, 1 H), 6.13 (d, J = 3.4 Hz, 1 H), 4.67 (d, J = 6.4 Hz, 1 H), 4.58 (d, J = 3.4 Hz, 1 H), 4.39 (d, J = 3.4 Hz, 2 H), 3.85 (s, 3 H), 3.78 (t, J = 15.1 Hz, 1 H), 3.22 (dd, J = 15.3, 2.9 Hz, 1 H), 2.89 (t, J = 13.3 Hz, 1 H), 1.27–1.70 (m, 10 H). ¹³C NMR (75 MHz, CDCl₃): δ = 173.2, 136.7, 131.9, 127.1, 122.5, 120.0, 118.5, 113.1, 111.6, 108.7, 105.3, 85.3, 82.1, 75.7, 56.2, 53.0, 52.8, 36.8, 35.9, 25.7, 25.2, 24.2, 23.9. MS (ESI): m/z = 429 [M + H]⁺. Anal. Calcd for C₂₃H₂₈N₂O₆: C, 64.47; H, 6.59; N, 6.54. Found: C, 64.51; H, 6.97; N, 6.71.Compound 4b: mp 96–98 °C; [α]_D –16.90 (c 0.5, CHCl₃). IR (KBr): 3336, 2937, 1737, 1450, 1076, 754 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.56 (s, 1 H, NH), 7.45 (d, J = 7.62 Hz, 1 H), 7.28 (d, J = 7.8 Hz, 1 H), 7.15 (t, J = 7.1 Hz, 1 H), 7.07 (t, J = 7.45 Hz, 1 H), 5.97 (d, J = 3.6 Hz, 1 H), 4.59–4.64 (m, 1 H), 4.53 (d, J = 3.6 Hz, 1 H), 4.34 (t, J = 2.7 Hz, 1 H), 4.28 (t, J = 2.7 Hz, 1 H), 4.16–4.23 (m, 1 H), 3.76 (s, 3 H), 3.13–3.20 (m, 3 H), 2.78–2.81 (m, 1 H), 1.25–1.64 (m, 10 H). ¹³C NMR (75 MHz, CDCl₃): δ = 173.9, 136.5, 130.5, 127.1, 122.6, 119.9, 118.4, 112.8, 111.5, 109.1, 104.7, 85.5, 80.4, 76.9, 52.9, 52.6, 51.0, 36.8, 35.9, 25.4, 25.2, 24.2, 23.9. MS (ESI): m/z = 429 [M + H]⁺. Anal. Calcd for C₂₃H₂₈N₂O₆: C, 64.47; H, 6.59; N, 6.54. Found: C, 64.31; H, 7.87; N, 7.01.10,11-O-Cyclohexylidene-12β-hydroxy(1-tetrahydro-3α-carbomethoxy-β-carboli-nyl)tetrahydrofuran (5a) and its isomer (5b): The residue obtained was purified by chromatography over silica gel using CHCl₃–petroleum-ether (90:10) eluent to afford 5a (630 mg, 73.5%) and CHCl₃ eluent to afford 5b (180 mg, 21%).Compound 5a: mp 142–144 °C; [α]_D –44.13 (c 0.5, CHCl₃). IR (KBr): 3447, 2934, 1712, 1448, 1022, 739 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.67 (s, 1 H, NH), 7.53 (d, J = 7.4 Hz, 1 H), 7.35 (d, J = 7.9 Hz, 1 H), 7.19 (t, J = 8.8 Hz, 1 H), 7.13 (t, J = 7.6 Hz, 1 H), 6.12 (d, J = 3.3 Hz, 1 H), 4.86 (d, J = 6.6 Hz, 1 H), 4.56 (d, J = 3.3 Hz, 1 H), 4.42 (t, J = 4.5 Hz, 1 H), 4.32 (d, J = 1.6 Hz, 1 H), 4.01 (t, J = 4.8 Hz, 1 H), 3.70 (s, 3 H), 3.12–3.24 (m, 2 H), 1.40–1.71 (m, 10 H). ¹³C NMR (75 MHz, CDCl₃): δ = 174.2, 136.6, 131.7, 127.1, 122.4, 119.8, 118.5, 113.0, 111.5, 107.5, 105.3, 85.3, 82.1, 75.7, 53.8, 52.7, 49.8, 36.7, 35.9, 25.2, 24.5, 24.3, 23.9. MS (ESI): m/z = 429 [M + H]⁺. Anal. Calcd for C₂₃H₂₈N₂O₆: C, 64.47; H, 6.59; N, 6.54. Found: C, 64.44; H, 7.17; N, 6.82.Compound 5b: mp 120–122 °C; [α]_D –10.54 (c 0.2, CHCl₃). IR (KBr): 2931, 1728, 1451, 1015, 744 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.33 (s, 1 H, NH), 7.48 (d, J = 7.2 Hz, 1 H), 7.37 (d, J = 8.1 Hz, 1 H), 7.20 (t, J = 8.2 Hz, 1 H), 7.14 (t, J = 8.2 Hz, 1 H), 6.05 (s, 1 H), 4.71 (s, 1 H), 4.55–4.66 (m, 2 H), 4.53 (s, 1 H), 3.84 (s, 3 H), 3.64 (dd, J = 11.2, 2.9 Hz, 1 H), 2.99 (t, J = 12.6 Hz, 1 H), 2.93 (t, J = 11.4 Hz, 1 H), 1.45–1.85 (m, 10 H). ¹³C NMR (75 MHz, CDCl₃): δ = 173.0, 136.6, 131.6, 127.3, 122.7, 120.2, 118.4, 112.9, 111.6, 109.2, 105.1, 85.2, 80.0, 76.9, 56.5, 53.3, 52.7, 37.0, 35.9, 25.8, 25.2, 24.3, 23.9. MS (ESI): m/z = 429 [M + H]⁺. Anal. Calcd for C₂₃H₂₈N₂O₆: C, 64.47; H, 6.59; N, 6.54. Found: C, 64.31; H, 7.07; N, 6.61.10,11-O-Cyclohexylidene-12β-allyloxy(1-tetrahydro-β-carbolinyl)tetrahydrofuran (6a) and its isomer (6b): The residue was purified by chromatography over silica gel using CHCl₃ to afford 6a (558 mg, 68%) and CHCl₃–MeOH (99:1) eluent to afford 6b (229.8 mg, 28%).Compound 6a: mp 56–58 °C; [α]_D –107.72 (c 0.1, CHCl₃). IR (KBr): 3449, 2935, 1449, 1163, 1022, 741 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.75 (s, 1 H, NH), 7.53 (d, J = 7.4 Hz, 1 H), 7.39 (d, J = 7.8 Hz, 1 H), 7.18 (t, J = 7.1 Hz, 1 H), 7.14 (t, J = 6.3 Hz, 1 H), 6.11 (d, J = 3.6 Hz, 1 H), 5.96 (m, 1 H), 5.20–5.36 (m, 2 H), 4.70–4.72 (d, J = 3.6 Hz, 1 H), 4.32–4.37 (m, 2 H), 4.06–4.18 (m, 3 H), 3.12–3.26 (m, 2 H), 2.71–2.84 (m, 2 H), 2.62 (br s, 1 H, NH), 1.25–1.75 (m, 10 H). ¹³C NMR (75 MHz, CDCl₃): δ = 136.2, 133.2, 134.4, 127.0, 122.0, 119.3, 118.4, 117.9, 113.6, 111.5, 109.2, 106.3, 88.0, 84.4, 84.3, 71.9, 52.9, 41.7, 36.6, 35.3, 25.2, 24.2, 23.8, 22.7. MS (ESI): m/z = 433 [M + Na]⁺. Anal. Calcd for C₂₄H₃₀N₂O₄: C, 70.22; H, 7.37; N, 6.82. Found: C, 70.12; H, 7.27; N, 6.92.Compound 6b: mp 58–60 °C; [α]_D –111.28 (c 0.1, CHCl₃). IR (KBr): 3443, 2935, 1449, 1113, 1018, 744 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.78 (s, 1 H, NH), 7.53 (d, J = 7.4 Hz, 1 H), 7.34 (d, J = 7.7 Hz, 1 H), 7.12 (t, J = 7.0 Hz, 1 H), 6.17 (t, J = 6.8 Hz, 1 H), 5.96–6.03 (m, 2 H), 5.12–5.42 (m, 3 H), 4.63 (d, J = 3.7 Hz, 1 H), 4.15–4.39 (m, 4 H), 2.50–3.42 (m, 5 H including NH), 1.25–1.85 (m, 10 H). ¹³C NMR (75 MHz, CDCl₃): δ = 136.1, 134.4, 134.1, 127.4, 119.4, 118.6, 118.3, 113.2, 112.8, 111.5, 109.0, 105.3, 83.8, 82.1, 81.7, 71.3, 51.6, 43.6, 36.7, 36.3, 25.2, 24.2, 24.0, 22.6. MS (ESI): m/z = 433 [M + Na]⁺. Anal. Calcd for C₂₄H₃₀N₂O₄: C, 70.22; H, 7.37; N, 6.82. Found: C, 69.72; H, 7.47; N, 7.02.10,11-O-Cyclohexylidene-12β-propyloxy(1-tetrahydro-3α-carbomethoxy-β-carbolinyl)tetrahydrofuran (7a) and its isomer (7b): The residue was purified by chromatography over silica gel using CHCl₃–petroleum-ether (90:10) eluent to afford 7a (757.5 mg, 80.5%) first and then 7b (108.2 mg, 11.5%).Compound 7a: mp 170–174 °C; [α]_D –175.04 (c 0.1, CHCl3). IR (neat): 3449, 2936, 1737, 1451, 1115, 746 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.60 (s, 1 H, NH), 7.52 (d, J = 7.7 Hz, 1 H), 7.36 (d, J = 7.8 Hz, 1 H), 7.19 (t, J = 7.8 Hz, 1 H), 7.12 (t, J = 7.5 Hz, 1 H), 6.08 (d, J = 3.4 Hz, 1 H), 4.66 (m, 2 H), 4.27 (m, 1 H), 4.11 (m, 1 H), 4.03 (m, 1 H), 3.72 (m, 4 H), 3.59 (m, 1 H), 3.18 (m, 2 H), 1.24–1.77 (m, 12 H), 1.06–1.02 (m, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 173.8, 135.9, 133.0, 126.6, 121.5, 118.9, 117.9, 112.6, 111.0, 106.5, 105.0, 83.4, 82.4, 81.2, 72.0, 53.8, 52.0, 48.3, 36.3, 35.8, 24.7, 24.0, 23.7, 23.5, 23.0, 10.5. MS (ESI): m/z = 493 [M + Na]⁺. Anal. Calcd for C₂₆H₃₄N₂O₆: C, 66.36; H, 7.28; N, 5.95. Found: C, 66.46; H, 7.37; N, 6.08.Compound 7b: ¹³C NMR (75 MHz, CDCl₃; obtained from a mixture with 7a): δ = 173.1, 136.1, 132.2, 127.1, 121.7, 119.4, 117.7, 112.5, 110.8, 109.0, 104.2, 83.6, 83.1, 81.4, 72.4, 56.2, 53.9, 52.5, 36.5, 35.7, 25.2, 24.2, 23.9, 23.4, 23.1, 10.5.10,11-O-Cyclohexylidene-12β-allyloxy(1-tetrahydro-3β-carbomethoxy-β-carboli-nyl)tetrahydrofuran (8) and 10,11-O-Cyclohexylidene-12β-allyloxy(1-tetrahydro-3α-carbomethoxy-β-carbolinyl)tetrahydrofuran (9): The residue obtained was purified by chromatography over silica gel using CHCl₃–petroleum-ether (90:10) eluent to afford 8 (915 mg, 97.5%) or 9 (919 mg, 98%), respectively.Compound 8: mp 62–64 °C; [α]_D –142.36 (c 0.1, CHCl₃). IR (KBr): 3448, 2935, 1738, 1448, 1165, 1023, 742 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.80 (s, 1 H, NH), 7.55 (d, J = 7.51 Hz, 1 H), 7.41 (d, J = 7.82 Hz, 1 H), 7.20 (t, J = 14.1 Hz, 1 H), 7.14 (t, J = 14.2 Hz, 1 H), 6.13–6.15 (m, 2 H), 5.36–5.48 (m, 2 H), 4.69 (d, J = 3.66 Hz, 1 H), 4.52 (d, J = 8.61 Hz, 2 H), 4.35 (dd, J = 5.22, 13.13 Hz, 2 H), 4.25 (d, J = 2.90 Hz, 1 H), 4.13 (dd, J = 12.6, 6.5 Hz, 1 H), 3.87 (s, 3 H), 3.25 (dd, J = 14.9, 2.9 Hz, 1 H), 2.95 (t, J = 15.8 Hz, 1 H), 2.60 (br s, 1 H, NH), 1.32–1.73 (m, 10 H). ¹³C NMR (75 MHz, CDCl₃): δ = 173.5, 136.5, 134.3, 133.8, 127.1, 122.0, 119.6, 119.4, 118.3, 113.3, 111.6, 107.9, 105.5, 83.9, 81.9, 81.7, 71.3, 56.5, 52.5, 52.3, 36.8, 36.4, 25.5, 25.2, 24.2, 24.0. MS (ESI): m/z = 491 [M + Na]⁺. Anal. Calcd for C₂₆H₃₂N₂O₆: C, 66.65; H, 6.88; N, 5.98. Found: C, 66.72; H, 7.07; N, 5.91.Compound 9: mp 60–62 °C; [α]_D –147.16 (c 0.1, CHCl₃). IR (KBr): 3446, 2934, 1736, 1451, 1164, 1021, 746 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 8.60 (s, 1 H, NH), 7.53 (d, J = 7.30 Hz, 1 H), 7.37 (d, J = 7.72 Hz, 1 H), 7.18 (t, J = 7.40 Hz, 1 H), 7.11 (t, J = 7.34 Hz, 1 H), 6.01–6.09 (m, 2 H), 5.46 (d, J = 17.20 Hz, 1 H), 5.32 (d, J = 10.46 Hz, 1 H), 4.67 (t, J = 19.8 Hz, 2 H), 4.25–4.36 (m, 2 H), 4.08–4.17 (m, 2 H), 4.01 (s, 1 H), 3.73 (s, 3 H), 3.17 (d, J = 3.61 Hz, 2 H), 2.56 (br s, 1 H, NH), 1.29–1.60 (m, 10 H). ¹³C NMR (75 MHz, CDCl₃): δ = 174.3, 136.4, 134.1, 133.6, 127.1, 122.0, 119.4, 118.6, 118.3, 113.1, 111.5, 107.1, 105.4, 83.8, 82.1, 81.7, 71.4, 54.2, 52.4, 48.6, 36.7, 36.2, 25.2, 24.6, 24.2, 24.0. MS (ESI): m/z = 491 [M + Na]⁺. Anal. Calcd for C₂₆H₃₂N₂O₆: C, 66.65; H, 6.88; N, 5.98. Found: C, 65.92; H, 7.27; N, 6.01.4,5-O-cyclohexyl-3-(2-methylallyloxy)tetrahydrofuran-2-carbaldehyde (2c): Colorless syrup; [α]_D ^18.9 –54.614 (c 1 mM, CHCl₃). IR (neat): 1737, 1672, 1168, 1022, 738 cm^–1. ¹H NMR (600 MHz, CDCl₃): δ = 9.62 (d, J = 2.1 Hz, 1 H), 6.07 (d, J = 3.42 Hz, 1 H), 4.86 (d, J = 8.94 Hz, 2 H), 4.55 (d, J = 3.42 Hz, 1 H), 4.49 (d, J = 3.42 Hz, 1 H), 4.22 (d, J = 4.14 Hz, 1 H), 3.91 (d, J = 12.36 Hz, 1 H), 3.79 (d, J = 12.42 Hz, 1 H), 1.61 (s, 3 H), 1.40–1.60 (m, 10 H). ¹³C NMR (75 MHz, CDCl₃): δ = 200.2, 140.8, 113.5, 113.3, 105.9, 84.6, 84.0, 81.7, 72.0, 36.7, 35.9, 24.8, 23.8, 23.6, 19.3. MS (ESI): m/z = 305 [M + Na]⁺. Anal. Calcd for C₁₅H₂₂O₅: C, 63.81; H, 7.85. Found: C, 63.77; H, 7.91.10,11-O-Cyclohexylidene-12β-(2-methylallyloxy)-(1-tetrahydro-3β-carbomethoxy-β-carboli-nyl)tetrahydro-furan (10) and 10,11-O-Cyclohexylidene-12β-(2-methyl-allyloxy)-(1-tetrahydro-3α-carbomethoxy-β-carbolinyl)-tetrahydrofuran (10): The residue obtained was purified by chromatography over silica gel using CHCl₃–MeOH (99:1) eluent to afford 10 (950 mg, 98.4%) or 11 (948 mg, 98.2%), respectively.Compound 10: mp 174–176 °C; [α]_D ^20.5 –41.29 (c 1 mM, CHCl₃). IR (KBr): 3452, 2933, 1739, 1448, 1165, 1025, 741 cm^–1. ¹H NMR (600 MHz, CDCl₃): δ = 8.75 (br s, 1 H, NH), 7.21–7.45 (m, 2 H), 7.05 (t, J = 9.8 Hz, 1 H), 6.97 (t, J = 9.6 Hz, 1 H), 5.82 (s, 1 H), 4.85–5.25 (m, 2 H), 4.67 (s, 2 H), 4.25–4.55 (m, 3 H), 3.80–4.15 (m, 2 H), 3.70 (m, 1 H), 3.55 (s, 3 H), 3.23 (m, 1 H), 2.84 (br s, 1 H), 1.10–1.70 (m, 13 H). ¹³C NMR (600 MHz, CDCl₃): δ = 172.5, 140.2, 137.0, 136.9, 125.9, 122.3, 119.4, 117.9, 114.1, 113.3, 111.9, 107.1, 104.6, 83.2, 81.1, 80.9, 74.2, 57.9, 56.7, 52.3, 36.1, 35.7, 24.7, 23.6, 23.5, 23.4, 19.3. MS (ESI): m/z = 506 [M + Na]⁺. Anal. Calcd for C₂₇H₃₄N₂O₆: C, 67.20; H, 7.10; N, 5.81. Found: C, 67.31; H, 7.11; N, 5.79.Compound 11: mp 166–168 °C; [α]_D ^19.5 –37.35 (c 1 mM, CHCl₃). IR (KBr): 3445, 2932, 1739, 1450, 1167, 1021, 747 cm^–1. ¹H NMR (600 MHz, CDCl₃): δ = 8.73 (br s, 1 H, NH), 7.40 (t, J = 8.94 Hz, 1 H), 7.20 (t, J = 4.8 Hz, 1 H), 7.09 (t, J = 7.56 Hz, 1 H), 7.02 (dd, J = 7.56 Hz, 1 H), 5.81 (s, 1 H), 4.80–5.10 (m, 2 H), 4.45–4.65 (m, 3 H), 4.00–4.20 (m, 2 H), 3.75–3.90 (m, 2 H), 3.45 (s, 3 H), 3.10 (s, 2 H), 2.98 (s, 1 H, NH), 1.63 (s, 3 H), 1.10–1.60 (m, 10 H). ¹³C NMR (600 MHz, CDCl₃): δ = 172.1, 141.0, 136.9, 136.4, 126.1, 122.5, 119.7, 118.4, 113.5, 113.2, 111.6, 104.7, 104.4, 83.4, 81.3, 81.1, 73.8, 54.5, 53.0, 50.5, 36.2, 35.8, 24.7, 23.8, 23.6 (2), 19.7. MS (ESI): m/z = 506 [M + Na]⁺. Anal. Calcd for C₂₇H₃₄N₂O₆: C, 67.20; H, 7.10; N, 5.81. Found: C, 67.21; H, 7.13; N, 5.75
• 14 It was not possible to isolate the minor diastereoisomer, which was formed as an inseparable mixture with the major diastereoisomer. Hence, the diastereomeric ratio (dr) was determined from LCMS retention time and peak area of the diastereoisomers in crude reaction mixture
• 15a Sharma GV. M, Begum A, Reddy KR, Sankar AR, Kunwar AC. Tetrahedron: Asymmetry 2003; 14: 3899
• 15b Smith AB, Rivero RA, Hale KJ, Vaccaro HA. J. Am. Chem. Soc. 1991; 113: 2092
• 15c Bhattacharjee A, Datta S, Chattopadhyay P, Ghoshal N, Kundu AP, Pal A, Mukhopadhyay R, Chowdhury S, Bhattacharjya A, Patra A. Tetrahedron 2003; 59: 4623
• 16a Kawalski P, Bojarski AJ, Mokrosz JL. Tetrahedron 1995; 51: 2737
• 16b Jackson AH, Smith AE. Tetrahedron 1968; 24: 403