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Improving Physical Properties via CH Oxidation: Chemical and Enzymatic Approaches
Author(s) -
Michaudel Quentin,
Journot Guillaume,
RegueiroRen Alicia,
Goswami Animesh,
Guo Zhiwei,
Tully Thomas P.,
Zou Lufeng,
Ramabhadran Raghunath O.,
Houk Kendall N.,
Baran Phil S.
Publication year - 2014
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201407016
Subject(s) - chemistry , solubility , betulin , natural product , molecule , organic chemistry , combinatorial chemistry , reactivity (psychology) , drug candidate , biochemistry , in vitro , medicine , alternative medicine , pathology
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 CH 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.