Synlett 2005(14): 2155-2158  
DOI: 10.1055/s-2005-872223
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Bile Acid Dimers Linked with 1,2,3-Triazole Ring at C-3, C-11, and C-24 Positions

Nilkanth G. Aher, Vandana S. Pore*
Organic Chemistry Synthesis Division, National Chemical Laboratory, Pune, 411008, India
Fax: +91(20)25893153; e-Mail: vs.pore@ncl.res.in;
Further Information

Publication History

Received 3 June 2005
Publication Date:
20 July 2005 (online)

Abstract

1,3-Dipolar cycloaddition of propargyl ester of a bile acid to an azide group attached at different positions of another bile acid gave three new 1,2,3-triazole-containing dimeric analogues in excellent yields.

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Typical Experimental Procedure. A solution of azide (1 mmol) and propargyl ester of bile acid (0.95 mmol) in t-BuOH (10 mL) was stirred at 60 °C for 15 min. Then, CuSO4·5H2O (5 mol% in 0.5 mL of H2O) and sodium ascorbate (20 mol% in 0.5 mL of H2O) were added to the reaction mixture and it was stirred at 60-65 °C for 3-12 h. The solvent was evaporated under reduced pressure to afford a crude product, which on purification by column chromatography on silica gel gave pure dimeric compounds containing 1,2,3-triazole moiety in 92-96% yield.
Spectral Data of Compound 8.
Yield 92%; mp 100-102 °C (EtOAc-hexane); [α]D 31 = +11.0 (c 0.6, CHCl3); TLC: R f = 0.56 (MeOH-CH2Cl2, 1:9). IR (CHCl3): 3431, 1728 cm-1. 1H NMR (200 MHz, CDCl3): δ = 0.66 (s, 3 H), 0.70 (s, 3 H), 0.91-1.00 (12 H), 3.61 (m, 1 H), 3.66 (s, 3 H, OCH3), 3.96 (br s, 1 H), 4.02 (br s, 1 H), 4.47 (m, 1 H), 5.20 (s, 2 H), 7.68 (s, 1 H, triazole H) ppm. 13C NMR (50 MHz, CDCl3): δ = 12.6, 17.2, 23.0, 23.1, 23.6, 25.9, 26.1, 26.8, 27.0, 27.4, 27.9, 28.6, 30.3, 30.6, 30.8, 31.1, 33.5, 33.6, 33.8, 34.0, 34.2, 35.1, 35.6, 35.9, 36.3, 42.0, 42.6, 46.4, 46.5, 47.0, 47.2, 47.9, 48.2, 51.4, 57.5, 61.0, 71.6, 72.9, 122.1, 142.2, 174.1, 174.6 ppm. MS (LC-MS): m/z calcd: 862.62 [M+ + 1]; found: 862.8 [M+ + 1], 884.8 [M+ + Na]. Anal. Calcd for C52H83N3O7: C, 72.44; H, 9.70; N, 4.87. Found: C, 72.17; H, 10.02; N, 4.60.

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Spectral Data of Compound 13.
Yield 96%; mp 136-138 °C (EtOAc-hexane); [α]D 31 = +9.84 (c 0.61, CHCl3); TLC: R f = 0.52 (MeOH-CH2Cl2, 0.5:9). IR (CHCl3): 3419, 1728 cm-1. 1H NMR (200 MHz, CDCl3): δ = 0.65 (s, 3 H), 0.66 (s, 3 H), 0.90-0.98 (12 H), 3.59 (m, 2 H), 3.96 (br s, 2 H), 4.31 (t, J = 7.07 Hz, 2 H, OCH2), 5.21 (s, 2 H), 7.60 (s, 1 H, triazole H) ppm. 13C NMR (75 MHz, CDCl3): δ = 12.3, 17.1, 17.4, 23.0, 23.6, 26.0, 26.9, 27.1, 27.5, 28.4, 30.2, 30.6, 31.0, 32.4, 33.3, 33.9, 35.1, 35.8, 36.1, 42.0, 46.3, 46.8, 47.9, 50.7, 57.3, 60.3, 63.5, 71.4, 72.9, 123.6, 142.7, 174.1 ppm. MS (LC-MS): m/z calcd: 834.63 [M+ + 1]; found: 834.7 [M+ + 1], 856.7 [M+ + Na]. Anal. Calcd for C51H83N3O6: C, 73.43; H, 10.03; N, 5.04. Found: C, 73.11; H, 9.82; N, 4.82.

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Spectral Data of Compound 16.
Yield 92%; mp 156-157 °C (EtOAc-hexane); [α]D 31 = +20.0 (c 0.61, CHCl3); TLC: R f = 0.4 (MeOH-CH2Cl2, 0.5:9). IR (CHCl3): 3411, 1728, 1674 cm-1. 1H NMR (200 MHz, CDCl3): δ = 0.67 (s, 3 H), 0.73 (d, J = 5.93 Hz, 3 H), 0.89 (s, 3 H), 0.96 (d, J = 5.69 Hz, 3 H), 1.18 (s, 3 H), 1.27 (s, 3 H), 2.00 (s, 3 H), 2.10 (s, 3 H), 3.45 (m, 1 H), 3.66 (s, 3 H, OCH3), 3.84 (br s, 1 H), 3.96 (br s, 1 H), 3.40 (m, 1 H), 5.02 (br s, 1 H) 5.24 (d, J = 2.02 Hz, 2 H, OCH2), 5.91 (d, J = 9.98 Hz, C-11 H attached to triazole), 7.83 (s, 1 H, triazole H) ppm. 13C NMR (75 MHz, CDCl3): δ = 11.2, 12.4, 17.2, 18.4, 21.2, 21.3, 22.5, 23.2, 24.0, 26.5, 27.1, 27.4, 28.2, 29.5, 30.1, 30.3, 30.8, 30.9, 31.0, 31.2, 34.6, 34.7, 35.1, 35.2, 35.4, 37.4, 38.1, 39.6, 41.5, 41.7, 42.2, 44.2, 46.5, 46.8, 47.4, 51.4, 52.4, 56.5, 57.4, 65.7, 68.3, 70.4, 71.9, 72.9, 73.2, 126.0, 142.7, 169.8, 170.5, 174.0, 174.3, 204.1 ppm. MS (LC-MS): m/z calcd: 992.61 [M+ + 1]; found: 992.7 [M+ + 1], 1014.7 [M+ + Na]. Anal. Calcd for C56H85N3O12: C, 67.78; H, 8.63; N, 4.23. Found: C, 67.43; H, 8.71; N, 3.97.