Based on the general framework of natural alkaloid deoxyvasicinone, forty dihydrooxazolo[5,4-d]pyrrolo[1,2-a]-pyrimidinone compounds were designed and synthesized through bioisosterism strategy. The novel compounds were confirmed by H-1 NMR, C-13 NMR and HRMS spectra. The main factors affecting the reactions of synthesis and the structure-activity relationships (SARs) were investigated. The activities of the target compounds against three cancer cell lines (MCF-7, HeLa and A549) were evaluated by methyl thiazolyl tetrazolium (MTT) in vitro. All the compounds were also evaluated for their antimicrobial activities by agar punch method. The results showed that 2-(naphthalen-l-y1)-6,7-dihydrooxazolo[5,4-d]-pynolo[1,2-a]pyrimidin-9(5H)-one (E12) and 2-(4-(trifluoromethoxy)pheny1)-6,7-dihydrooxazolo[5,4-d]pyrrolo[1,2-a]pyrimidin-9(5H)-one (E39) exhibited relatively better anti-proliferative activities against HeLa and MCF-7 cancer cell lines, with the half maximal inhibitory concentration (IC50) values of (4.59 +/- 0.10), (6.89 +/- 1.26) mu mol.L-1, respectively. 2-((3R,5R,7R)-Adamantan-l-yl)-6,7-dihydrooxazolo[5,4-d]pyrrolo[1,2-a]pyrimidin-9(5H)-one (E6) and 2-(3,5-dichloropheny1)-6,7-dihydro-oxazolo[5,4-d]pyrrolo[1,2-a]lpyrimidin-9(5H)-one (E28) showed good antimicrobial activity to C. albicans, E. coli and S. aureus.