Currently, harmful algal blooms are being one of ever-increasing global environmental problems. Much attention has been paid to the use of natural products as the selective algaecides due to their low toxicity, high selectivity and eco-friendly properties. In the present study, the thiazole alkaloid (1), originally isolated from Thermoactino-myces strain TM-64, was shown to exhibit potent algicidal activity against three typically harmful cyanobacterial algae, S. obliqnus, M. aeruginosa, and C. pyrenoidosa. Based on our previous work, a practical, scalable synthesis of alkaloid (1) was developed and reaction could be readily scaled up to more than 100 g. In addition, twenty-six analogues of alkaloid (1) by replacement of tryptamine moiety with different aromatic and aliphatic amines were also prepared. The bioassay results showed that most of these derivatives displayed potent algicidal activity against three harmful algae S. obliqnus, M. aeruginosa, and C. pyrenoidosa with IC50 values in the range of 1.5-5.0 μg/mL. Amongst them, compounds (10) and its hydrochloric salt (10S) were found to reveal powerful growth inhibitory activity against harmful cyanobacterial algae with IC50 values as low as 0.08 μg/mL, comparable to those of commercial algicide CuSO4 and herbicide Diuron.