A series of calycanthaceous alkaloid analogs have been synthesized in excellent yields. All the target compounds were evaluated in vitro for biological activity against a broad range of plant pathogen fungi, bacteria and human pathogenic fungi, and some of the designed compounds exhibited potential activity in the primary assays. Notably, Compound b7 illustrated higher degrees of activity against Aspergillu sflavu than amphotericin B, with a minimal inhibitory concentration value of 15.63 µg·mL−1. Compound b7 displayed the most effective activity among the tested calycanthaceous analogs and might be a novel potential leading compound for further development of antifungal agent.