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DOI: 10.1055/s-2005-872224
Design and Synthesis of Novel 20-epi Analogues of Calcitriol with Restricted Side Chain Conformation
Publication History
Publication Date:
20 July 2005 (online)
Abstract
The design and efficient preparation of two 20-epi analogues of calcitriol with restricted side chain conformation is described. The formation of the tetrahydropyran ring was achieved via zinc chloride mediated etherification of alcohols. Docking experiments show that these novel analogues could be interesting synthetic targets.
Key words
synthesis - vitamin D - analogues - nitriles - diols - drugs
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References
All new compounds exhibited satisfactory 1H NMR and 13C NMR, analytical, and/or high-resolution mass spectral data.
15Compound 5a: 1H NMR (300 MHz, CDCl3): δ = 6.37 (1 H, d, J = 11.3 Hz, =CH-6 or =CH-7), 6.01 (1 H, d, J = 11.30 Hz, =CH-6 or =CH-7), 5.31 (1 H, s, CH2-19), 4.99 (1 H, s, CH2-19), 4.42 (1 H, dd, J = 7.69, 4.27 Hz, CHOH), 4.22 (1 H, m, CHOH), 3.66 (1 H, d, J = 11.52 Hz, CH2O), 3.47 (1 H, t, J = 11.38 Hz, CH2O), 2.82 (1 H, m), 2.59 (1 H, m), 2.31 (2 H, m), 1.18 (3 H, s, CH3-26 or CH3-27), 1.16 (3 H, s, CH3-26 or CH3-27), 0.81 (3 H, d, J = 6.80 Hz, CH3-21), 0.52 (3 H, s, CH3-18). 13C NMR (CDCl3): δ = 147.67 (C=), 143.08 (C=), 132.91 (C=), 125.15 (CH=), 117.20 (CH=), 111.90 (CH2=), 71.01 (C-25), 70.87 (CH), 66.87 (CH), 62.76 (CH2), 56.35 (CH), 53.50 (CH), 46.16 (C-13), 45.30 (CH2), 42.89 (CH2), 39.85 (CH2), 39.13 (CH), 37.89 (CH), 37.16 (CH2), 31.35 (CH3), 29.12 (CH2), 26.96 (CH2), 24.86 (CH2), 23.45 (CH2), 22.20 (CH2), 21.57 (CH3), 14.30 (CH3), 12.10 (CH3). HRMS: m/z calcd for C28H45O3: 429.3369; found: 429.3390.
16Compound 5b: 1H NMR (300 MHz, CDCl3): δ = 6.36 (1 H, d, J = 11.3 Hz, =CH-6 or =CH-7), 6.01 (1 H, d, J = 11.3 Hz, =CH-6 or =CH-7), 5.31 (1 H, s, CH2-19), 4.99 (1 H, s, CH2-19), 4.42 (1 H, dd, J = 8.0, 4.3 Hz, CHOH), 4.23 (1 H, m, CHOH), 3.53 (1 H, t, J = 11.3, CH2O), 3.43 (1 H, dd, J = 11.1, 3.0 Hz, CH2O), 2.82 (1 H, dd, J = 10.5, 3.7 Hz), 2.58 (1 H, dd, J = 9.9, 3.3 Hz), 2.30 (1 H, dd, J = 13.5, 6.4 Hz), 1.19 (3 H, s, CH3-26 or CH3-27), 1.17 (3 H, s, CH3-26 or CH3-27), 0.77 (3 H, d, J = 6.8 Hz, CH3-21), 0.54 (3 H, s, CH3-18). 13C NMR (CDCl3): δ = 147.67 (C=), 142.93 (C=), 132.99 (C=), 124.96 (CH=), 117.14 (CH=), 111.74 (CH2=), 71.35 (C-25), 70.82 (CH), 66.87 (CH), 65.85 (CH2), 56.38 (CH), 53.08 (CH), 46.02 (C-13), 45.27 (CH2), 42.89 (CH2), 39.80 (CH2), 38.70 (CH), 36.55 (CH2), 36.27 (CH), 31.34 (CH3), 29.69 (CH2), 27.25 (CH2), 23.52 (CH2), 22.12 (CH2), 21.51 (CH3), 19.73 (CH2), 14.39 (CH3), 11.89 (CH3). HRMS: m/z calcd for C28H45O3: 429.3369; found: 429.3377.