Citation: SHANG Ruo-Feng, XU Shui-Jin, YI Yun-Peng, AI Xin, LIANG Jian-Ping. Syntheses, Crystal Structures and Antibacterial Evaluation of Two New Pleuromutilin Derivatives[J]. Chinese Journal of Structural Chemistry, ;2016, 35(4): 529-536. doi: 10.14102/j.cnki.0254-5861.2011-0896 shu

Syntheses, Crystal Structures and Antibacterial Evaluation of Two New Pleuromutilin Derivatives

1.
a Key Laboratory of New Animal Drug Project of Gansu Province;Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture;Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou 730050, China;
b Yancheng Youhua Pharmaceutical & Chemical Technology Co.
b Yancheng Youhua Pharmaceutical & Chemical Technology Co., Ltd., Yancheng 224555, China

Received Date: 14 July 2015
Available Online: 16 October 2015
Fund Project: Supported by Basic Scientific Research Funds in Central Agricultural Scientific Research Institutions (No. 1610322014003) (No. 1610322014003)

Two new pleuromutilin derivatives, 14-O-[(4-amino-6-methoxyl-pyrimidine-2-yl)-thioacetyl] mutilin (4) and 14-O-[4-amino-1-methyl-6-oxo-1,6-dihydropyrimidin-2-yl)thioacetyl] mutilin (5), were synthesized and structurally characterized by IR, NMR spectra, HRMS and single-crystal X-ray diffraction. These compounds contain a 5-6-8 tricyclic carbon skeleton and a pyrimidine ring. Compound 4 is in the monoclinic system, space group P12₁1 with a=10.2517(4), b=12.5655(4), c=10.3435(4) Å, V=1315.69(8) Å³, Z=2, Dc=1.309 g/cm³, F(000)=558, μ=0.166 mm^-1, S=1.047, R=0.0457 and wR=0.0934 for 4721 unique reflections (R_int=0.0322) with I > 2σ(I). Compound 5 belongs to the orthorhombic system, space group P2₁2₁2₁ with a=7.3667(4), b=13.9990(7), c=29.0434(13) Å, V=2995.1(2) Å³, Z=4, Dc=1.250 g/cm³, F(000)=1216, μ=0.153 mm^-1, S=1.031, R=0.0545 and wR=0.0982 for 5242 unique reflections (R_int=0.0476) with I>2σ(I)). The in vitro antibacterial activity study showed the title compounds 4 and 5 displayed slightly less activity against methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus epidermidis (MRSE), and lower potent against Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis) when compared to those of tiamulin fumarate.
- pleuromutilin,
- single-crystal structure,
- antibacterial activities
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沈阳化工大学材料科学与工程学院沈阳 110142