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

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Abstract

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 (Rint = 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 (Rint = 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.

Key words： pleuromutilin single-crystal structure antibacterial activities

Received: 14 July 2015 Published: 11 April 2016

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Supported by Basic Scientific Research Funds in Central Agricultural Scientific Research Institutions (No. 1610322014003)
and the Agricultural Science and Technology Innovation Program (ASTIP, No. CAAS-ASTIP-2014-LIHPS-04)

Corresponding Authors: liangjp1963@163.com E-mail: liangjp1963@163.com

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	SHANG Ruo-Feng
	XU Shui-Jin
	YI Yun-Peng
	AI Xin
	LIANG Jian-Ping

Cite this article:

SHANG Ruo-Feng,XU Shui-Jin,YI Yun-Peng, et al. Syntheses, Crystal Structures and Antibacterial Evaluation of Two New Pleuromutilin Derivatives[J]. CHINESE JOURNAL OF STRUCTURAL CHEMISTRY, 2016, 35(4): 529-536.

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http://manu30.magtech.com.cn/jghx/EN/ OR http://manu30.magtech.com.cn/jghx/EN/Y2016/V35/I4/529

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