Rooperol (1,5-bis(3’,4’-dihydroxyphenyl)pent-1-en-4-yne) is a naturally occurring bis-catechol that was originally isolated from the African Potato (Hypoxis hemerocallidea). Rooperol shows promising anti-cancer activity in vitro, but it is rapidly and completely metabolized to inactive phase-II metabolites in vivo. To address this problem, synthetic analogues of rooperol may be synthesized in which some or all of the catechol groups are replaced with more metabolically stable isosteres, with the intent of designing a molecule that has the same anti-cancer effects of rooperol, but is not metabolized as rapidly. Our initial efforts in establishing a structure-activity relationship for these analogues involves the preparation and evaluation of a series of symmetrical (in which both catechols are replaced with isosteres) and unsymmetrical analogues (in which only one catechol is replaced). Our original total synthesis of rooperol and its analogues employed a Friedel-Crafts alkylation using tetrachlorocyclopropene that was not general and did not scale well. Here, we report a more scalable synthesis that has enabled the preparation of rooperol and analogues on scales required for in vitro and in vivo biological evaluation.

Scalable synthesis of rooperol and analogues

256th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.