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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.

New esters 2-5 that contain 6-chloropyridine groups characteristic of the alkaloid epibatidine were prepared by acylation of 20-hydroxyecdysone (1) by 6-chloronicotinoylchloride.Ecdysteroids are an extensive group of natural steroids united by a common chemical structure and biological activity as shedding and metamorphosis hormones of insects and other invertebrates [1].The plant Serratula sogdiana was previously studied in detail for ecdysteroid content [2][3][4]. The goal of our work was the chemical modification of natural ecdysteroids to increase the biological activity of the starting compound.One of the distinguishing features of the ecdysteroid structure is a large number of hydroxyls that differ widely in their reactivity. As a result, ecdysteroids are exceedingly suitable starting materials for preparing new biologically active compounds using various chemical transformations [5].We have previously synthesized several 3-(6-chloronicotinates) of 3β,5α,6β-trihydroxysteroids and 3β,5-dihydroxy-6-ketosteroids. A distinguishing feature of the compounds resulting from this was the presence in their structures of the α-chloropyridine moiety, which is characteristic of the alkaloid epibatidine, a natural analgesic isolated from the Ecuadorian frog Epipedobates tricolor [7]. The α-chloropyridine moiety is an important structural element that is responsible for the high biological activity of several modern neonicotinoid insecticides [8]. The pyridine ring occurs in the structure of the phytoecdysteroid diploclidine, which was isolated from Diploclisia glaucescens (Menispermaceae) [9].In continuation of previous work [6], we synthesized 6-chloronicotinates of 20-hydroxyecdysone (1), one of the principal ecdysteroids that is widely distributed in plants and represents a convenient starting material for preparing new biologically active derivatives [1]. Acylation of 1 by 6-chloronicotinoylchloride in Py at room temperature was carried out for 4 d. The acylation catalyst was 4-dimethylaminopyridine. It was found that a mixture of four 6-chloronicotinates was formed under these conditions. Column chromatography could separate them into pure components, producing mono-, di-, tri-, and tetra-6-chloronicotinates, the structures of which were established by analyzing PMR and 13 C NMR spectra. The most interesting feature of these was that the labile 14α-hydroxy-Δ 7 -6-keto group characteristic of starting 20-hydroxyecdysone (1) was retained in all acylation products. PMR spectra of the acylation products could rather simply indicate the number of 6-chloronicotinic acids bonded to the 20-hydroxyecdysone from the number of proton resonances of the pyridine rings. OR 4 R 1 O R 2 O H OH OR 3 O HO 1 -5 1: R 1 = R 2 = R 3 = R 4 = H 2: R 1 = Z, R 2 = R 3 = R 4 = H 3: R 1 = R 3 = Z, R 2 = R 4 = H 4: R 1 = R 2 = R 3 = Z, R 4 = H 5: R 1 = R 2 = R 3 = R 4 = Z Z = N Cl CO

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