Stability, Kinetic, and Mechanistic Investigation of 1,8-Self-Immolative Cinnamyl Ether Spacers for Controlled Release of Phenols and Generation of Resonance and Inductively Stabilized Methides

Siddharth S Matikonda; Jessica M Fairhall; Joel D A Tyndall; Sarah Hook; Allan B Gamble

doi:10.1021/acs.orglett.6b03695

Stability, Kinetic, and Mechanistic Investigation of 1,8-Self-Immolative Cinnamyl Ether Spacers for Controlled Release of Phenols and Generation of Resonance and Inductively Stabilized Methides

Org Lett. 2017 Feb 3;19(3):528-531. doi: 10.1021/acs.orglett.6b03695. Epub 2017 Jan 12.

Authors

Siddharth S Matikonda¹, Jessica M Fairhall¹, Joel D A Tyndall¹, Sarah Hook¹, Allan B Gamble¹

Affiliation

¹ New Zealand's National School of Pharmacy, University of Otago , Dunedin 9054, New Zealand.

PMID: 28080067
DOI: 10.1021/acs.orglett.6b03695

Abstract

Three cinnamyl ether spacers (non-methyl, α-methyl, and γ-methyl) for caging of phenols have been synthesized and are physiologically stable. When triggered, the γ-methyl spacer releases phenols (pK_a 7.8 and 9.8) with a t_1/2 < 30 s and <2 min in aqueous and aqueous-organic solvent, respectively. The α-methyl spacer releases a phenol (pK_a 7.8) with a t_1/2 = 27 and 54 min. For the γ-methyl spacer, the results suggest the presence of a resonance and inductively stabilized aza-cinnamyl methide.

Publication types

Research Support, Non-U.S. Gov't