title: Efficient Synthesis of a Series of Novel Octahydroquinazoline-5-ones via a Simple on-Water Urea-Catalyzed Chemoselective Five-Component Reaction.
abstract: Multicomponent reactions (MCRs) have become a powerful tool for drug discovery and development owing to their advantages of fast and efficient construction of a large library of products with complexity and diversity. However, conventional MCRs usually proceed in environmentally unfriendly organic solvents rather than in water, a green solvent used by nature for biological chemistry. Herein, a simple and efficient on-water urea-catalyzed chemoselective five-component reaction (5CR) has been developed for the synthesis of a series of novel octahydroquinazoline-5-ones (6), the derivatives of quinazolinones possessing diverse biological activities. The molecular structure of 6{1,1,12} has been confirmed by single-crystal X-ray diffraction. The 5CR can proceed at room temperature under normal atmospheric pressure in good yields and afford a large library of octahydroquinazoline-5-ones with various aromatic and aliphatic substituents at N-1, C-2, and N-3. In addition, a green method has been developed for the synthesis of enaminones, important intermediates in the 5CR and in synthetic chemistry.
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University , 1838 Guangzhou Avenue North, Guangzhou 510515, China.
authors.forename: Sichao
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University , 1838 Guangzhou Avenue North, Guangzhou 510515, China.
authors.forename: Shufang
authors.initials: S
authors.lastname: Zhong
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University , 1838 Guangzhou Avenue North, Guangzhou 510515, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University , 1838 Guangzhou Avenue North, Guangzhou 510515, China.
authors.forename: Wenhua
authors.initials: W
authors.lastname: Chen
authors.affiliation: Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University , 1838 Guangzhou Avenue North, Guangzhou 510515, China.
authors.forename: Qiuhua
authors.initials: Q
authors.lastname: Zhu
mesh_terms: D002384:Catalysis; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D015394:Molecular Structure; D052999:Quinazolinones / Q000138:chemical synthesis* / Q000737:chemistry; D014508:Urea / Q000737:chemistry*; D014867:Water / Q000737:chemistry*
chemical_list: D052999:Quinazolinones; D014867:Water; D014508:Urea
keywords: enaminones; multicomponent reaction; octahydroquinazoline-5-ones; synthetic method; water solvent