898-84-0Relevant articles and documents
Chemical methods for the conversion of Prednisolone to 11-β-hydroxy-1,4-androstadiene-3,17-dione
Surya Pratap, Pinnama Reddy,Shafi, Syed,Naaz, Fatima,Devanna, Nayakanti
, p. 1827 - 1830 (2015)
Several microbial transformations of steroids to 17-keto cortisones through side chain cleavage have been presented in the literature; however, yields and product selectivity in these methods were low. In the present study, some new methods have been identified for the side chain cleavage of prednisolone (1) to form 11- β-hydroxy-1,4-androstadiene-3,17-dione (11- β-hydroxy ADD). Prednisolone upon reaction with zinc chloride in dry THF results in the formation of cleavage product in good yield (76%). 11- β-hydroxy ADD (2) has been formed in moderate yield (60%) under the Reformatsky reaction conditions by reacting with zincate. While performing the Wittig reaction using stable ylides, again results in the formation of compound 2 in good yield (56%). Side chain cleavage of prednisolone was confirmed from the physical and analytical data and similar when compared with the literature reports.
Toxicity of prednisolone, dexamethasone and their photochemical derivatives on aquatic organisms
DellaGreca, Marina,Fiorentino, Antonio,Isidori, Marina,Lavorgna, Margherita,Previtera, Lucio,Rubino, Maria,Temussi, Fabio
, p. 629 - 637 (2004)
Light exposure of aqueous suspensions of prednisolone and dexamethasone causes their partial phototransformation. The photoproducts, isolated by chromatographic techniques, have been identified by spectroscopic means. Prednisolone, dexamethasone and their photoproducts have been tested to evaluate their acute and chronic toxic effects on some freshwater chain organisms. The rotifer Brachionus calyciflorus and the crustaceans Thamnocephalus platyurus and Daphnia magna were chosen to perform acute toxicity tests, while the alga Pseudokircheneriella subcapitata (formerly known as Selenastrum capricornutum) and the crustacean Ceriodaphnia dubia to perform chronic tests. The photochemical derivatives are more toxic than the parent compounds. Generally low acute toxicity was found. Chronic exposure to this class of pharmaceuticals caused inhibition of growth population on the freshwater crustacean C. dubia while the alga P. subcapitata seems to be less affected by the presence of these drugs.
Microwave assisted synthesis and biomedical potency of salicyloyloxy and 2-methoxybenzoyloxy androstane and stigmastane derivatives
Penov Ga?i, Katarina M.,Djurendi?, Evgenija A.,Szécsi, Mihály,Gardi, János,Csanádi, János J.,Klisuri?, Olivera R.,Doj?inovi?-Vuja?kovi?, Sanja V.,Nikoli?, Andrea R.,Savi?, Marina P.,Ajdukovi?, Jovana J.,Oklje?a, Aleksandar M.,Koji?, Vesna V.,Saka?, Marija N.,Jovanovi?-?anta, Suzana S.
, p. 31 - 40 (2015)
A convenient microwave assisted solvent free synthesis as well as conventional synthesis of salicyloyloxy and 2-methoxybenzoyloxy androstane and stigmastane derivatives 7-19 from appropriate steroidal precursors 1-6 and methyl salicylate is reported. The microwave assisted synthesis in most cases was more successful regarding reaction time and product yields. It was more environmentally friendly too, compared to the conventional method. The antioxidant activity and cytotoxicity of the synthesized derivatives were evaluated in a series of in vitro tests, as well as their inhibition potency exerted on hydroxysteroid dehydrogenase enzymes (Δ5-3βHSD, 17βHSD2 and 17βHSD3). All of the tested compounds were effective in OH radical neutralization, particularly compounds 9, 11 and 14, which exhibited about 100-fold stronger activity than commercial antioxidants BHT and BHA. In DPPH radical scavenging new compounds were effective, but less than reference compounds. 2-Methoxybenzoyl ester 10 exhibited strong cytotoxicity against MDA-MB-231 cells. Most compounds inhibited growth of PC-3 cells, where salicyloyloxy stigmastane derivative 15 showed the best inhibition potency. Compounds 9, 10 and 11 were the best inhibitors of 17βHSD2 enzyme. X-ray structure analysis and molecular mechanics calculations (MMC) were performed for the best cytotoxic agents, compounds 10 and 15. A comparison of crystal and MMC structures of compounds 10 and 15 revealed that their molecules conformations are stable even after releasing of the influence of crystalline field and that the influence of crystal packing on molecular conformation is not predominant.
Electrochemically Enabled One-Pot Multistep Synthesis of C19 Androgen Steroids
Sommer, Florian,Kappe, C. Oliver,Cantillo, David
supporting information, p. 6044 - 6049 (2021/03/15)
The synthesis of many valuable C19 androgens can be accomplished by removal of the C17 side chain from more abundant corticosteroids, followed by further derivatization of the resulting 17-keto derivative. Conventional chemical reagents pose significant drawbacks for this synthetic strategy, as large amounts of waste are generated, and quenching of the reaction mixture and purification of the 17-ketosteroid intermediate are typically required. Herein, we present mild, safe, and sustainable electrochemical strategies for the preparation of C19 steroids. A reagent and catalyst free protocol for the removal of the C17 side chain of corticosteroids via anodic oxidation has been developed, enabling several one-pot, multistep procedures for the synthesis of androgen steroids. In addition, simultaneous anodic C17 side chain cleavage and cathodic catalytic hydrogenation of a steroid has been demonstrated, rendering a convenient and highly atom economic procedure for the synthesis of saturated androgens.
Preparation method of loteprednol etabonate intermediate
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Paragraph 0010; 0031; 0034; 0037; 0040, (2021/07/14)
The invention provides a preparation method of a loteprednol etabonate intermediate. The preparation method comprises the following steps: carrying out dehydration reaction on 11 alpha-hydroxyl-ADD and a dehydrating agent in an organic solvent to obtain a compound II; carrying out a first addition reaction on the compound II and a halogenating reagent in an organic solvent in the presence of an acid catalyst, and adding a quenching agent to carry out a quenching reaction after the reaction is finished, so as to obtain a compound III; carrying out reduction reaction on the compound III and a metal reducing agent in an organic solvent in the presence of an acid catalyst to obtain a compound IV; carrying out secondary addition reaction on the compound IV and a cyaniding reagent in an organic solvent in the presence of a basic catalyst to obtain a compound V; and carrying out hydrolysis reaction on thecompound V and an acid reagent in an organic solvent to obtain a compound VI, wherein the compound VI is the loteprednol etabonate intermediate. The preparation method saves energy, reduces consumption, and is easy to operate, high in yield and good in purity.
HYDROXYSTEROID COMPOUNDS, THEIR INTERMEDIATES, PROCESS OF PREPARATION, COMPOSITION AND USES THEREOF
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Page/Page column 48, (2016/02/09)
The present invention relates to novel steroidal compounds of formula (I), process for preparation of the same and composition comprising these compounds.
Bismuth(III) triflate-catalyzed direct conversion of corticosteroids into highly functionalized 17-ketosteroids by cleavage of the C17-dihydroxyacetone side chain
Pinto, Rui M. A.,Salvador, Jorge A. R.,Le Roux, Christophe,Paixao, Jose A.
supporting information; experimental part, p. 8488 - 8491 (2010/02/28)
(Chemical Equation Presented) The use of bismuth(III) triflate as catalyst for the direct conversion of corticosteroids into highly functionalized 17-ketosteroids by cleavage of the C17-dihydroxyacetone side chain is reported. This catalytic process is very chemoselective, since functionalities of the starting corticosteroids, such as Δ4-3-keto, Δ1,4-3-keto, 11β-hydroxyl, and 9β,11β-epoxide, remained intact.
Detailed study of oxidative esterification and elimination reactions undergone by a steroidal 17α-benzoyloxy-20-oxo-21-aldehyde
Lewbart,Annan,Arison,Springer,Gould
, p. 373 - 378 (2007/10/02)
The reaction of 17α-benzoyloxy-11β-hydroxy-3,20-dioxo-1,4-pregnadien-21-al as the hemiacetal (1) with methanol:acetic acid:potassium cyanide:manganese dioxide followed by acetylation and preparative HPLC of the reaction mixture afforded 11 crystalline products. These products can be conveniently divided into three categories representing side-chain cleavage and oxidative esterification with or without elimination of the benzoyloxy group. Of special interest was the stereospecific formation of the C-17 cyanohydrin acetate 4a and the cis Δ17(20) enol acetate methyl ester 5. On the other hand, nonstereospecific addition of HCN to the side chain gave the C-20 epimeric cyanohydrin acetates 7a and 7b. The use of activated versus nonactivated MnO2 plays a major role in determining the quantitative distribution of the products. It was also discovered that even in the absence of MnO2, the reaction goes to completion. A proposed mechanism which explains the formation of all products is presented.
Microbial hydroxylation of steroids. 11. Hydroxylation of A-nor-, B-homo-Δ1-, and Δ1-testosterone acetates by Rhizopus arrhizus
Holland, Herbert L.,Chenchaiah, P. Chinna
, p. 1127 - 1131 (2007/10/02)
The testosterone derivatives A-nortestosterone acetate and B-homo-Δ1-testosterone acetate have been incubated with Rhizopus arrhizus, a fungus which hydroxylates testosterone at the C-6β and C-11α positions.These modes of hydroxylation were also observed for the A-nor steroid.The B-homo steroid, however, was oxidized at C-2β and concurrently hydroxylated at C-6β and C-7aβ (but not at C-11) by R. arrhizus. Δ1 steroids of conventional skeleton were hydroxylated at C-11α by R. arrhizus; in addition, Δ1-androstenedione was epoxidized at the 1,2β position.No C-6 hydroxylation of conventional Δ1,4-3-ketosteroids was observed..
