Marine microorganisms continue to serve as a prolific source of new natural products. In an effort to identify novel secondary metabolites, we used analytical HPLC with photodiode array (PDA) detection to profile crude fermentation extracts, matching UV spectra against an in-house library. This approach identified unique UV peaks in extracts from Nereus strain NPS008187, a Streptomyces sp. isolated from a marine sediment collected in Alaska. Follow-up isolation and spectroscopic structure elucidation yielded three new pyrrolosesquiterpenes (glaciapyrroles A, B, and C) and three known diketopiperazines (cyclo(leucyl-prolyl), cyclo(isoleucyl-prolyl), and cyclo(phenylalanyl-prolyl)). These pyrrolosesquiterpenes are unique in nature, as pyrroles incorporated into terpenes are rare. Glaciapyrrole B may be derived from the epoxide derivative glaciapyrrole C during extraction and isolation. Glaciapyrrole A exhibited cytotoxicity against colorectal adenocarcinoma HT-29 and melanoma B16-F10 tumor cell lines with an IC50 value of 180 µM.