title: Improving physical properties via C-H oxidation: chemical and enzymatic approaches.
abstract: Physicochemical properties constitute a key factor for the success of a drug candidate. Whereas many strategies to improve the physicochemical properties of small heterocycle-type leads exist, complex hydrocarbon skeletons are more challenging to derivatize because of the absence of functional groups. A variety of C-H oxidation methods have been explored on the betulin skeleton to improve the solubility of this very bioactive, yet poorly water-soluble, natural product. Capitalizing on the innate reactivity of the molecule, as well as the few molecular handles present on the core, allowed oxidations at different positions across the pentacyclic structure. Enzymatic oxidations afforded several orthogonal oxidations to chemical methods. Solubility measurements showed an enhancement for many of the synthesized compounds.
authors.affiliation: Department of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037 (USA).
authors.forename: Quentin
authors.initials: Q
authors.lastname: Michaudel
authors.forename: Guillaume
authors.initials: G
authors.lastname: Journot
authors.forename: Alicia
authors.initials: A
authors.lastname: Regueiro-Ren
authors.forename: Animesh
authors.initials: A
authors.lastname: Goswami
authors.forename: Zhiwei
authors.initials: Z
authors.lastname: Guo
authors.forename: Thomas P
authors.initials: TP
authors.lastname: Tully
authors.forename: Lufeng
authors.initials: L
authors.lastname: Zou
authors.forename: Raghunath O
authors.initials: RO
authors.lastname: Ramabhadran
authors.forename: Kendall N
authors.initials: KN
authors.lastname: Houk
authors.forename: Phil S
authors.initials: PS
authors.lastname: Baran
mesh_terms: D001688:Biological Products / Q000737:chemistry; D002244:Carbon / Q000737:chemistry*; D006859:Hydrogen / Q000737:chemistry*; D010084:Oxidation-Reduction; D012995:Solubility
chemical_list: D001688:Biological Products; D002244:Carbon; D006859:Hydrogen
keywords: CH activation; medicinal chemistry; oxidation; radical reactions; terpenoids