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

doi:10.1055/s-2005-872223

LETTER

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;

Abstract

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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.

Key words

bile acids - steroidal dimers - click chemistry - 1,3-dipolar cycloaddition - 1,2,3-triazole

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References

<A NAME="RG16005ST-1A">1a</A> Davis AP. Chem. Soc. Rev. 1993, 243

<A NAME="RG16005ST-1B">1b</A> Li Y. Dias JR. Chem. Rev. 1997, 97: 283

<A NAME="RG16005ST-1C">1c</A> Wallimann P. Marti T. Fürer A. Diederich F. Chem. Rev. 1997, 97: 1567

<A NAME="RG16005ST-1D">1d</A> Kolehmainen E. Tamminen J. Molecules 2001, 6: 21

<A NAME="RG16005ST-1E">1e</A> Virtanen E. Kolehmainen E. Eur. J. Org. Chem. 2004, 3385

<A NAME="RG16005ST-2">2</A> Bortolini O. Cora V. Fantin G. Medici A. Chem. Lett. 1996, 335

<A NAME="RG16005ST-3">3</A> Burrows CJ. Sauter RA. J. Inclusion Phenom. 1987, 5: 117

<A NAME="RG16005ST-4">4</A> Kinneary JF. Roy TM. Albert JS. Yoon H. Wagler TR. Shen L. Burrows CJ. J. Inclusion Phenom. 1989, 7: 155

<A NAME="RG16005ST-5">5</A> McKenna J. McKenna JM. Thornthwaite DW. J. Chem. Soc., Chem. Commun. 1977, 809

<A NAME="RG16005ST-6A">6a</A> Tamminen J. Kolehmainen E. Haapala M. Linnanto J. Synthesis 2000, 1464 ; and references cited therein

<A NAME="RG16005ST-6B">6b</A> Pandey PS. Rai R. Singh RB. J. Chem. Soc., Perkin Trans. 1 2002, 918 ; and references cited therein

<A NAME="RG16005ST-6C">6c</A> Pandey PS. Singh RB. Tetrahedron 2002, 58: 355

<A NAME="RG16005ST-7">7</A> Davis AP. Wareham RS. Angew. Chem. Int. Ed. 1999, 38: 2978 ; and references cited therein

<A NAME="RG16005ST-8A">8a</A> Kohmoto S. Sakayori K. Kishikawa K. Yamamoto M. J. Chem. Soc., Perkin Trans. 2 1999, 833

<A NAME="RG16005ST-8B">8b</A> Potluri VK. Maitra U. J. Org. Chem. 2000, 65: 7764 ; and references cited therein

<A NAME="RG16005ST-9">9</A> Salunke DB. Hazra BG. Pore VS. Bhat MK. Nahar PB. Deshpande MV. J. Med. Chem. 2004, 47: 1591

<A NAME="RG16005ST-10A">10a</A> Lakhvich FA. Lis LG. Akhrem AA. Russ. Chem. Rev. 1984, 53: 582

<A NAME="RG16005ST-10B">10b</A> Burbiel J. Bracher F. Steroids 2003, 68: 287

<A NAME="RG16005ST-10C">10c</A> Fouace S. El kihel L. Dherbomez M. Letourneux Y. Bioorg. Med. Chem. Lett. 2001, 11: 3011

<A NAME="RG16005ST-11A">11a</A> Odds FC. Brown AJP. Gow NAR. Trends Microbiol. 2003, 11: 272 ; and references cited therein

<A NAME="RG16005ST-11B">11b</A> Cooper AB. Wright JJ. Ganguly AK. Desai J. Loebenberg D. Parmeqiani R. Feingold DS. Sud IJ. J. Chem. Soc., Chem. Commun. 1989, 898

<A NAME="RG16005ST-12A">12a</A> Rostovtsev VV. Green LG. Fokin VV. Sharpless KB. Angew. Chem. Int. Ed. 2002, 41: 2596

<A NAME="RG16005ST-12B">12b</A> Tornoe CW. Christensen C. Meldal M. J. Org. Chem. 2002, 67: 3057

<A NAME="RG16005ST-13">13</A> Suarez PL. Gandara Z. Gomez G. Fall Y. Tetrahedron Lett. 2004, 45: 4619

<A NAME="RG16005ST-14">14</A> Suh BC. Jeon HB. Posner GH. Silverman SM. Tetrahedron Lett. 2004, 45: 4623

<A NAME="RG16005ST-15">15</A> Chittaboina S. Xie F. Wang Q. Tetrahedron Lett. 2005, 46: 2331

<A NAME="RG16005ST-16">16</A> Davis AP. Perez-Payan MN. Synlett 1999, 991

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.

<A NAME="RG16005ST-18">18</A> Li C. Peters AS. Meredith EL. Allman GW. Savage PB. J. Am. Chem. Soc. 1998, 120: 2961

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.

<A NAME="RG16005ST-20">20</A> Salunke DB. Hazra BG. Gonnade RG. Bhadbhade MM. Pore VS. Tetrahedron 2005, 61: 3605

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.