Pyrrole is an important core of some bioactive marine natural products, and thus, its preparative methods have been much contemplated. Our interests in this area have led to successful development of general synthetic methods for symmetric, as well as asymmetric, 3,4-diaryl pyrroles, as they are the common subunit in marine natural products known as lamellarins, ningalins, purpurones, and lukianols. Lamellarins have been shown to exhibit cytotoxicity, inhibit cell division, exhibit immunomodulatory activity, inhibit HIV-1 integrase, and, more importantly, reverse multidrug-resistance in some cancer cell lines. Some lamellarins have been evaluated for their cytotoxicity and investigated for their molecular mode(s) of biological activities. Ningalins and lukianols are expected to possess some similar activities, since they are related biosynthetically to the lamellarins. Our interest in the lamellarins has led us to devise and develop a number of successful synthetic routes, including the use of more environmentally friendly solid-supported reagents, which offer crucial applications in “green chemistry”. Their utilization in the reactions leads to less amount of solvent used while minimizing an additional step involving water to separate organic and aqueous materials, thus produces less waste. In addition, extensive studies of Cu(I)-mediated/microwave (MW)-assisted C-O and C-N bond formations have been performed using subcritical water as solvent, which also conforms with the “green chemistry” theme to affect the ring closure of the lactone and lactam moieties to furnish lamellarins, isolamellarins, and the nitrogen-analog azalamellarins. Thus far, over 100 structurally related analogs of lamellarins have been successfully prepared and their SARs have been established. Currently, our effort has been focused on streamlining the structural requirements of lamellarins while incorporating functional groups to enhance aqueous solubility and assessing the drug-likeness.

   Sharing some structural similarities to the lamellarins, ningalin C, which is a more complex marine natural product, has been successfully prepared in only a few chemical steps. In addition, new synthetic methods for the combretastatins, which are non-alkaloidal cis-stilbenes and structurally related to lamellarins, have been developed to prepare new analogs with potentially better biological parameters against various cancer cell lines.