Citation: Ying Nie, Yin Sun, Qi-Dong You. Synthesis and antibacterial activity of novel 10, 11-epoxy acylide erythromycin derivatives[J]. Chinese Chemical Letters, ;2013, 24(3): 183-185. shu

Synthesis and antibacterial activity of novel 10, 11-epoxy acylide erythromycin derivatives

Ying Nie ^a ,
Yin Sun ^b ,
Qi-Dong You ^b,,

1.
a Experimental Center of Pharmaceutical Science, China Pharmaceutical University, Nanjing 210009, China;
2.
b Jiangsu Key Laboratory of Drug Design and Optimization, China Pharmaceutical University, Nanjing 210009, China

Corresponding author: Qi-Dong You,
Received Date: 21 January 2013
Available Online: 4 February 2013

A series of novel acylide derivatives have been synthesized from clarithromycin A via a facile procedure. The C-3 modifications involved replacing the natural C-3 cladinosyl group in clarithromycin core with different aryl-piperzine sidechain via chemical synthesis. Meanwhile a distinctive intermediate with 10,11-epoxy moiety was obtained. The structure and stereochemistry of this novel structure were confirmed via NMR and X-ray crystallography. Potential anti-bacterial activities against both Grampositive and Gram-negative bacteria were reported. Because of existence of C10,11-epoxide, these derivatives can be used as intermediates for further structural modification.
- Epoxide acylide erythromycin derivatives,
- Synthesis,
- Single-crystal X-ray diffraction,
- Resistance antibacterial activity
1. [1]
  [1] P. Kurath, P. Jones, R. Egan, et al., Acid degradation of erythromycin A and erythromycin B, Experentia 27 (1971) 362.
2. [2]
  [2] K. Krowick, A. Zamojski, Chemical modification of erythromycin I. 8,9-anhydro-6⁹-hemiketal of A, J. Antibiot. 26 (1973) 569-574.
3. [3]
  [3] R. Leclercq, Mechanisms of resistance to macrolides and lincosamides: nature of the resistance elements and their clinical implications, Clin. Infect. Dis. 34 (2002) 482-492.
4. [4]
  [4] J.C. Pechere, Macrolide resistance mechanisms in Gram-positive cocci, Int. J. Antimicrob. Agents 18 (2001) S25-S28.
5. [5]
  [5] T. Tanikawa, T. Asaka, M. Kashimura, et al., Synthesis and antibacterial activity of a novel series of acylides: 3-O-(3-pyridyl) acetylerythromycin A derivatives, J. Med. Chem. 46 (2003) 2706-2715.
6. [6]
  [6] T. Ly, S. Yat, M. Zhenkun, 6-O-alkyl-2-nor-2-substituted ketolide derivatives, U.S. Patent. 0103140 (2002).
7. [7]
  [7] A.K. Ghosh, K. Jae-Hun, An enantioselective synthesis of the C1 C9 segment of antitumor macrolide peloruside A, Tetrahedron Lett. 44 (2003) 3967-3969.
8. [8]
  [8] Selected characteristic data for the compounds. 9: Yellow powder; mp 91-93℃, IR (KBr, cm^-1): v 1706, 1729, 1748; ¹H NMR (300 MHz, CDCl₃): δ7.28-7.40 (m, 5H, Ph-H), 5.03 (dd, 1 H, J = 2.3 Hz and 9.2 Hz, H₁₃), 4.69 (dd, 1 H, J = 2.3 Hz and 8.2 Hz, H₂), 3.10 (s, 3H, C6-OCH₃), 1.88 (s, 3H, C20-OCOCH₃), 1.66 (s, 3H, C10-CH₃); ESI-MS m/z (%): 772 (M+Na⁺). X-ray analysis: C₃₉H₅₉NO₁₃, M_r = 749.90, crystal size 0.586 mm×0.173 mm×0.049 mm, orthorhombic in p2_1/n with a = 14.024(3), b = 28.998(6), c = 10.915(2)Å, a, b, g = 90°, V = 3185.0(9)Å³, Dcalu = 1.151 Mg/m³, and Z = 4, absorption coefficient 0.087 mm^-1, computing structure solution SHELXL-97, theta range for data collection 1.61 to 25.508, limiting indices -16≤h≤10,-35≤k≤19,-13≤l≤12, reflection collected 23690, refinement method full-matrix least-squares, final R indices [I > 2 sigma (I)] R₁ = 0.1016, wR₂ = 0.2461, R indices (all data) R₁ = 0.2601, wR₂ = 0.3102, goodness-of-fit on F² 0.894, largest difference peak 0.360 eAÅ³, largest difference hole 0.236 eÅ³. 14a: White crystal; mp 127-129℃, IR (KBr, cmÅ^-1): v 1165, 1706, 1741; ¹H NMR (300 MHz, CDCl₃): δ 7.09-7.28 (m, 5H, Ph-H), 5.01 (dd, 1 H, J = 2.4 Hz and 10.4 Hz, H₁₃), 3.23 (s, 3H, C6-OCH₃), 3.18 (m, 4H, 2 CH₂ in piperazinyl), 2.65 (m, 6H, 2 CH₂ in piperazinyl and CH₂N), 2.39 (s, 6H, N(CH₃)₂), 1.64 (s, 3H, C10-OCH₃); ESI-MS m/z (%): 803 (M+H⁺). 14b: White crystal; mp 117-119℃, IR (KBr, cm^-1): v 1164, 1512, 1741; ¹H NMR(300 MHz, CDCl₃): δ 6.81-7.27 (m, 4H, Ph-H), 5.01 (dd, 1 H, J = 2.3 Hz and 10.3 Hz, H₁₃), 3.76 (s, 3H, Ar-OCH₃), 3.12 (s, 3H, C6-OCH₃), 3.07 (m, 4H, 2 CH₂ in piperazinyl), 2.68 (m, 6H, 2 CH₂ in piperazinyl and CH₂N), 2.46 (s, 6H, N(CH₃)₂), 1.62 (s, 3H, C10-CH₃); ESI-MS m/z (%): 833 (M+H⁺). 14c: White crystal; mp 105-106℃, IR (KBr, cm^-1): y 1164, 1741; ¹H NMR (300 MHz, CDCl₃): δ 6.81-7.27 (m, 4H, Ph-H), 5.01 (dd, 1 H, J = 2.7 Hz and 10.5 Hz, H₁₃), 3.22 (s, 3H, C6-OCH₃), 3.15 (m, 4H, 2 CH₂ in piperazinyl), 2.63 (m, 6H, 2 CH₂ in piperazinyl and CH₂N), 2.38 (s, 6H, N(CH₃)₂), 2.17 (s, 3H, Ar-CH₃), 1.65 (s, 3H, C10-OCH₃); ESI-MS m/z (%): 817 (M+H⁺). 14d: White crystal; mp 112-113℃, IR (KBr, cm^-1): v 1164, 1742; ¹H NMR (300 MHz, CDCl₃): δ 7.03-7.37 (m, 4H, Ph-H), 5.01 (dd, 1 H, J = 6.5 Hz and 14.0 Hz, H₁₃), 3.24 (s, 3H, C6-OCH₃), 3.11 (m, 4H, 2 CH₂ in piperazinyl), 2.66 (m, 6H, 2 CH₂ in piperazinyl and CH₂N), 2.40 (s, 6H, N(CH₃)₂), 1.65 (s, 3H, C10-OCH₃); ESI-MS m/z (%): 871 (M+H⁺). 14e: White crystal; mp 114-116℃, IR (KBr, cm^-1): v 1164, 1742; ¹H NMR (300 MHz, CDCl₃): δ 6.90-7.45 (m, 4H, Ph-H), 5.00 (dd, 1 H, J = 2.4 Hz and 10.3 Hz, H₁₃), 3.23 (s, 3H, C6-OCH₃), 3.14 (m, 4H, 2 CH₂ in piperazinyl), 2.82 (m, 6H, 2 CH₂ in piperazinyl and CH₂N), 2.29 (s, 6H, N(CH₃)₂), 1.64 (s, 3H, C10-OCH₃); ESI-MS m/z (%): 821 (M+H⁺). 14f: White crystal; mp 124-125℃, IR (KBr, cm^-1): v 1163, 1742; ¹H NMR (300 MHz, CDCl₃): δ 6.95-7.18 (m, 4H, Ph-H), 5.00 (dd, 1 H, J = 2.2 Hz and 10.2 Hz, H₁₃), 3.24 (s, 3H, C6-OCH₃), 3.19 (m, 4H, 2 CH₂ in piperazinyl), 2.83 (m, 6H, 2 CH₂ in piperazinyl and CH₂N), 2.29 (s, 9H, Ph-CH₃ and N(CH₃)₂), 1.63 (s, 3H, C10-OCH₃); ESI-MS m/z (%): 817 (M+H⁺). 14g: White crystal; mp 134-136℃, IR (KBr, cm^-1): v 1164, 1741; ¹H NMR (300 MHz, CDCl₃): δ 6.87-7.02 (m, 4H, Ph-H), 5.00 (dd, 1 H, J = 2.7 Hz and 10.1 Hz, H₁₃), 3.86 (s, 3H, Ph-OCH₃), 3.23 (s, 3H, C6-OCH₃), 3.15 (m, 4H, 2 CH₂ in piperazinyl), 2.69 (m, 6H, 2 CH₂ in piperazinyl and CH₂N), 2.31 (s, 6H, N(CH₃)₂), 1.64 (s, 3H, C10-OCH₃); ESI-MS m/z (%): 833 (M+H⁺). 14h: White crystal; mp 99-107℃, IR (KBr, cm^-1): v 1165, 1741; ¹H NMR (300 MHz, CDCl₃): δ 8.18 (d, 1 H, Pyr-H₆), 7.47 (t, 1 H, Pyr-H₄), 6.63 (t, 2H, Pyr-H3, Pyr-H₅), 5.00 (dd, 1 H, J = 3.7 Hz and 8.9 Hz, H₁₃), 3.22 (s, 3H, C6-OCH₃), 3.18 (m, 4H, 4H, 2 ₂ in piperazinyl), 2.61 (m, 6H, 2 CH₂ in piperazinyl and CH₂N), 2.41 (s, 6H, N(CH₃)₂), 1.65 (s, 3H, C10-OCH₃); ESI-MS m/z (%): 842 (M+H⁺). 14i: White crystal; mp 100-102℃, IR (KBr, cm^-1): v 1164, 1742; ¹H NMR (300 MHz, CDCl₃): δ 6.90-6.99 (m, 3H, Ph-H), 5.00 (dd, 1 H, J = 2.7 Hz and 10.1 Hz, H₁₃), 3.23 (s, 3H, C6-OCH₃), 3.11 (m, 4H, 2 CH₂ in piperazinyl), 2.66 (m, 6H, 2 CH₂ in piperazinyl and CH₂N), 2.26 (s, 6H, N(CH₃)₂), 2.25 (s, 3H, Ph-CH₃), 2.22 (s, 3H, Ph-CH₃), 1.65 (s, 3H, C10-OCH₃); ESI-MS m/z (%): 832 (M+H⁺). 14j: White crystal; mp 114-115℃, IR (KBr, cm^-1): y 1165, 1741; ¹H NMR (300 MHz, CDC₁₃): δ 6.80-7.07 (m, 3H, Ph-H), 5.00 (dd, 1 H, J = 2.7 Hz and 10.1 Hz, H₁₃), 3.22 (s, 3H, C6-OCH₃), 3.14 (m, 4H, 2 CH₂ in piperazinyl), 2.65 (m, 6H, 2 CH₂ in piperazinyl and CH₂N), 2.31 (s, 6H, N(CH₃)₂), 2.24 (s, 3H, Ph-CH₃), 2.21 (s, 3H, Ph-CH₃), 1.65 (s, 3H, C10-OCH₃); ESI-MS m/z (%): 832 (M+H⁺).
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沈阳化工大学材料科学与工程学院沈阳 110142