Synthesis of Ecdysteroids and Related Compounds

Abstract

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Synthesis of new α-chloropyridine derivatives of steroidal 3β,5α,6β-triols and 3β,5-dihydroxy-6-ketones

“…A mixture of 1 (2.10 g, 5 mmol) (prepared by the literature method [6]), 2-chloro-5-chloromethylpyridine (0.97 g, 6 mmol) (prepared by the literature method [5]), tetra-n-butylammonium bromide (0.32 g, 1 mmol), toluene (60 mL), and aqueous NaOH solution (10 mL, 50%) was stirred, heated to 105-110°C for 25 h, treated with additional 2-chloro-5-chloromethylpyridine (0.97 g, 6 mmol), stirred and heated at 105-110°C for 29.5 h, cooled to room temperature, treated with dichloroethane (50 mL) and water (40 mL), and shaken. The resulting precipitate was filtered off, washed on the filter successively with water (10 mL) and dichloroethane (10 mL), and dried in air to afford 1 (0.98 g, 46.7%).…”

“…The reaction of triol 1 or dihydroxyketones 2 and 3 with 2-chloro-5-chloromethylpyridine produced the corresponding 2-chloropyridine-5-methyl ethers in which the α-chloropyridine ring was bonded to the corresponding steroids not through an ester bond as before [1] but through a metabolically more inert ether bond. 2-Chloro-5-chloromethylpyridine is widely used in the production of neonicotinoids [3], a convenient synthesis of which we recently developed [5].Reaction of 3β,5α,6β-trihydroxysteroid 1 with 2-chloro-5-chloromethylpyridine in toluene in the presence of aqueous NaOH solution and tetra-n-butylammonium bromide formed two monoethers that were isolated in yields of 30 and 5.5%. Their structures as the 3-and 6-regioisomers were established using spectral data.…”

“…The reaction of triol 1 or dihydroxyketones 2 and 3 with 2-chloro-5-chloromethylpyridine produced the corresponding 2-chloropyridine-5-methyl ethers in which the α-chloropyridine ring was bonded to the corresponding steroids not through an ester bond as before [1] but through a metabolically more inert ether bond. 2-Chloro-5-chloromethylpyridine is widely used in the production of neonicotinoids [3], a convenient synthesis of which we recently developed [5].…”

Synthesis of 20-hydroxyecdysone 6-chloronicotinates

“…A solution of 1 (24 mg, 0.05 mmol), 6-chloronicotinoylchloride (70.4 mg, 0.40 mmol) (prepared by the literature method [6]), and 4-dimethylaminopyridine (2 mg) in Py (1.5 mL) was held at room temperature for 4 d. The Py was removed from the mixture by repeated evaporation with benzene in a rotary evaporator under vacuum from a water aspirator and at a bath temperature of less than 30°C. The dry solid was separated into components by chromatography over a column of silica gel with elution by CH 2 Cl 2 :CH 3 OH mixtures with gradually increasing CH 3 OH content from 0.5% to 10%.…”

Synthesis of α-chloropyridine-containing oximes of 3β,5-dihydroxy-6-ketosteroids

“…Therefore, we assumed that such chemical modification of 3E,5-dihydroxy-6-ketosteroids would increase their insecticidal activity. We synthesized previously [11,12] derivatives of these steroids containing D-chloropyridine rings bonded to the 3-hydroxyl.In order to prepare the target O-substituted 3E,5-dihydroxy-6-ketosteroid oximes, a synthetic method was required for the previously unknown O-(2-chloropyridin-5-ylmethyl)hydroxylamine (3), which we synthesized through a series of reactions including reaction of phthalic anhydride with hydroxylamine, subsequent alkylation of the resulting N-hydroxyphthalimide by 2-chloro-5-chloromethylpyridine (1) to form the phthalimide (2), and hydrazinolysis of it to give the target compound.Our initial attempts to synthesize the corresponding O-substituted oxime via reaction of the 3E,5D-dihydroxy-6-ketone (4) with the O-substituted hydroxylamine (3) in the presence of acid catalysts were unsuccessful. It was found that this reaction did not occur in the presence of acetic acid.…”