Novel side chain ω-fluorinated ecdysteroid analogues were obtained starting from ω-functionalized ecdysteroids. Thus, the reaction of diacetonides of 26, derivatives with diethylaminosulfur trifluoride (DASТ) involves replacement of the terminal hydroxyl group and dehydration at the 14-position to give 25RS-fluoro-and 24-fluoro-14-anhydro analogues of ecdysteroids.
IntroductionEcdysteroids are known as insect hormones which control molting, metamorphosis, and reproduction [1]. Some ecdysteroids act as hormone antagonists, disturbing insect molting process [2]; however, these compounds cannot efficiently affect the population of insects, which has acquired defense mechanisms against exogenous ecdysteroids during evolution. In view of this fact, a synthesis of novel ecdysteroid analogues would provide compounds for efficient regulation of vital processes in insects [3].The non-hormonal biological activity of ecdysteroids towards mammals is intensively studied [4][5][6]. It has been reported that non-polar ecdysteroids possess chemo-sensitizing activity towards various cancer cell lines [7][8][9][10]. The fluorination of steroids, juvenile hormones, and pheromones can influence the biological activity of these compounds [11]. The interest in fluorinated analogues of natural compounds is caused by features of the fluorine atom, which significantly affects the biological activity and the metabolic stability of a molecule due to high electronegativity, and small size and to low polarizability of the C-F bond. Thus, the introduction of fluorine atom in natural products is the attractive strategy to obtain new leads for drug discovery [12]. The most common synthetic route to fluorinated derivatives is fluorination with various nucleophilic reagents [13]. Among them, diethylaminosulfur trifluoride (DAST) is widely used in deoxyfluorination of oxygen-containing organic compounds; moreover, this reagent is effective for geminal fluorination of acid-sensitive substrates such as aldehydes and ketones [14].The aim of the present study was to involve new side chain analogues of 20-hydroxyecdysone in the DAST-fluorination and to extend the scope of the reaction to the synthesis of biologically active fluorinated analogues of ecdysteroids. In this regard, we began our research from the study of DAST fluorination of the side chain-modified oxoecdysteroids 1 and 2, which were obtained by the ozonolysis of ∆ 24,25 -and ∆ 25,26 -derivatives of 20-hydroxyecdysone [16]. It should be noted that 20-hydroxyecdysone is a polyhydroxylated molecule with three secondary and three tertiary hydroxyl groups and it reacts with the DAST reagent to give a complex reaction mixture. DAST fluorination of ecdysteroids 1 and 2
Results and Discussionhaving an acid-sensitive γ-hydroxy-α,β-enone moiety gave only 14-anhydro derivatives 3 and 4. Moreover, it was found that the oxo groups of ecdysteroid side chain are inert to the DAST-mediated geminal difluorination. That is why terminal alcohols 5 and 6 were chosen as alternative precursors for t...
