Synthesis of New 20-Hydroxyecdysone o-Chlorobenzoyl Derivatives

Abstract

Acylation by o-chlorobenzoylchloride produced new 20-hydroxyecdysone (1) derivatives with o-chlorobenzoyl fragments (2)(3)(4)(5) in the 20-hydroxyecdysone.Phytoecdysteroids are widely distributed in hundreds of plant species belonging to dozens of families and genera. A total of >400 ecdysteroids including >300 of plant origin have been identified. Recent research found that practically all terrestrial and aquatic plants have genes for synthesizing ecdysteroids [1].Chemical modifications of 20-hydroxyecdysone derivatives are currently of great interest. 20-Hydroxyecdysone is the most common phytoecdysteroid and offers a convenient synthon for preparing new biologically active compounds for medical and household needs [2]. 20-Hydroxyecdysone is polyhydroxylated with six hydroxyls. Three secondary ones on C 2 , C 22 , and C 3 are more reactive; on C 25 , C 20 , and C 14 , less reactive [3,4]. A study of the chemical modifications of 20-hydroxyecdysone defined the reactivities of the hydroxyls toward conjugation and placed them in the following order of decreasing reactivity: C 2 > C 22 > C 3 > C 25 > C 20 >> C 14 [5].We synthesized o-chlorobenzoyl derivatives of 20-hydroxyecdysone. Acylation of 20-hydroxyecdysone used o-chlorobenzoylchloride in Py at 45-50°C for 2 h [6]. Therefore, a mixture of 20-hydroxyecdysone mono-, di-, tri-, and tetraesters was rather readily obtained by direct esterification with a large excess of the acid chloride.Column chromatography of the mixture separated pure components such as the novel 2-O-(o-chlorobenzoyl)-20-hydroxyecdysone (2), 2,3-di-O-(o-chlorobenzoyl)-20-hydroxyecdysone (3), 2,3,22-tri-O-(o-chlorobenzoyl)-20-hydroxyecdysone (4), and 2,3,22,25-tetra-O-(o-chlorobenzoyl)-20-hydroxyecdysone (5). Their structures were elucidated using PMR and 13 C NMR spectra and 2D experiments. It is of utmost importance to note that the labile 14D-hydroxy and ' 7 -6-ketone groups characteristic of starting 20-hydroxyecdysone (1) were retained in all acylation products. The number of o-chlorobenzoyl groups attached to 20-hydroxyecdysone could be determined rather simply from the PMR spectral data of the acylation products.

Preparation and Analysis of the NMR Spectra of the Pharmaceutical Substance«oose-11,12,13»

“…Mis-screening of protons H-2 and H-3 methine groups of A (δ=4.33-4.43 ppm, dd, 2H, and J=4.6 and 6.0 Hz) were explained by the effect of neighboring OH groups [22]. The most high-frequency signal doublet (5.57 ppm, 2H, and J=2.5 Hz) can be attributed to the proton of the atom C-7, coupled with the 6-keto group [23].…”