Improving Physical Properties via CH Oxidation: Chemical and Enzymatic Approaches1. (22nd September 2014)

• Record Type: Journal Article
• Authors: Michaudel, Quentin; Journot, Guillaume; Regueiro‐Ren, Alicia; Goswami, Animesh; Guo, Zhiwei; Tully, Thomas P.; Zou, Lufeng; Ramabhadran, Raghunath O.; Houk, Kendall N.; Baran, Phil S.
• Is Part Of: Angewandte Chemie. Volume 126:Number 45(2014)
• Page Start: 12287
• Page End: 12292
• Publication Date: 2014-09-22
• Subjects: Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201407016
• Languages: English
• ISSNs: 0044-8249

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <p>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.</p> </abstract>