Syntheses of methylated catechins and theaflavins using 2-nitrobenzenesulfonyl group to protect and deactivate phenol.

An efficient and versatile synthetic method for labile polyphenols was established using 2-nitrobenzenesulfonate (Ns) as a protecting group for phenol. This methodology provides regio- and stereoselective access to a range of methylated catechins, such as methylated epigallocatechin gallates, that are not readily available from natural sources. In addition, biomimetic synthesis of theaflavins from catechins was accomplished using Ns protection to minimize undesired side reactions of electron-rich aromatic rings during oxidation, enabling construction of the complex benzotropolone core in a single-step oxidative coupling reaction. Availability of these compounds will aid detailed structure-biological activity relationship studies of catechins.