Azido-Coronatine: A Useful Platform for “Click Chemistry”-Mediated Probe Synthesis for Bioorganic Studies

Abstract

We report on the development of azide-coronatine as a useful platform for azide alkyne cycloaddition (''click chemistry'')-mediated synthesis of molecular probes. (þ)-Azido-coronatine was synthesized in 10 steps with 11% yield using improved synthesis of coronafacic acid, in which the highly exo-selective Diels-Alder reaction (endo:exo > 1:25) is the key step. Azido coronatine was as effective as the original coronatine in a stomatal opening assay, and was easily modified to a fluorescein isothiocyanate (FITC)-labeled probe with high yield.

Dual function of coronatine as a bacterial virulence factor against plants: possible COI1–JAZ-independent role

“…We carried out SAR studies of 1 for stomatal reopening activity using guard cells of A. thaliana as a model plant. We synthesized a racemic mixture of methyl coronafacate (5) using our previously reported procedure, 16 with minor modication (Scheme S1 †). The resulting (AE)-5 was then separated by chiral HPLC using a CHIRALPAK IA column to obtain naturally occurring (+)-5 with an optical purity of 99.3% ee (Fig.…”

“…We previously reported the development of an azide-tagged COR (14) for use as a COR-based "Click"-mediated molecular probe. 27 Fluorescein-labeled COR (15) was easily prepared from 14 using "Click Chemistry" (Fig. 8A).…”

Synthetic Approaches to Coronafacic Acid, Coronamic Acid, and Coronatine

“…Reduction and subsequent acid-mediated hydrolysis/elimination delivered 32, which underwent hydrogenation to rapidly deliver the advanced intermediate 26. Significantly, the (±)-4 prepared using this route was then used in the synthesis of a biological probe, 17 illustrating the potential of this route to deliver sufficient quantities of (±)-4 for further study.…”

“…15 In addition, there has been significant interest in the structurally simpler 1 mimic coronalon (6), 16 and the oxime derivative of 1 (7), which has been reported to possess antagonist activity in the jasmonic acid signalling pathway ( Figure 3). 5 Lastly, 1 has been functionalised to allow its incorporation into biological probes, 17,18 and, furthermore, antibodies have been developed for the quantification of 1 in competitive enzyme-linked immunosorbent assays (ELISAs). 19 Figure 3 Coronalon (6) and COR oxime (7) Through the efforts of various research groups, there is an emerging SAR associated with 1.…”

“…Following this initial synthesis, Ueda and co-workers reported an improvement of their synthetic sequence, 17 28 was considerably more selective. Reduction and subsequent acid-mediated hydrolysis/elimination delivered 32, which underwent hydrogenation to rapidly deliver the advanced intermediate 26.…”