Enantioselective divergent syntheses of several polyhalogenated plocamium monoterpenes and evaluation of their selectivity for solid tumors

The family of polyhalogenated monoterpenes from Plocamium counts over a hundred known members. Using glyceraldehyde acetonide as a chiral-pool precursor, an enantioselective and divergent strategy was developed that provides a blueprint for the synthesis of many of the small yet complex acyclic members of this family. The broad applicability of this approach is demonstrated with the short, eight-step synthesis of four natural products and three analogues. These syntheses are the first of any members of the acyclic polyhalogenated Plocamium monoterpenes and permitted the evaluation of their selectivity against a range of tumor cell lines. Glyceraldehyde acetonide serves as a chiral glyoxal equivalent and a linchpin for the enantioselective synthesis of several acyclic polyhalogenated monoterpenes from the red algae Plocamium. Several of these compounds demonstrate selective toxicity towards solid-tumor cell lines over leukemia cell lines, as well as low-micromolar cytotoxicity towards the HCT-116 human colon carcinoma cell line.