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Synlett 2013; 24(1): 85-89
DOI: 10.1055/s-0032-1317632
letter
© Georg Thieme Verlag Stuttgart · New York

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

Prasun K. Pradhan*
,
Debkumar Nandi
a   Chemistry Department, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India   Fax: +91(33)23673058   Email: drpkp@yahoo.com
,
Soma Das Pradhan
b   Department of Chemistry (DDE), Vidyasagar University, Midnapore, 721102, India
,
Parasuraman Jaisankar
a   Chemistry Department, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India   Fax: +91(33)23673058   Email: drpkp@yahoo.com
,
V. S. Giri
a   Chemistry Department, Indian Institute of Chemical Biology, 4 Raja S. C. Mullick Road, Jadavpur, Kolkata, 700032, India   Fax: +91(33)23673058   Email: drpkp@yahoo.com
› Author Affiliations
Further Information

Publication History

Received: 18 August 2012

Accepted after revision: 23 October 2012

Publication Date:
10 December 2012 (online)

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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
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  • 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