Reaktionen an 16‐Methylen‐ und 16‐Hydroxymethylen‐17‐Keto‐steroiden

Brückner, Klaus; Irmscher, Klaus; Werder, F. v.; Bork, Karl‐Heinz; Metz, Harald

doi:10.1002/cber.19610941111

Cited by 25 publications

(9 citation statements)

References 16 publications

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“…Thus, two additional cyclic tautomers (2d and 2e) can contribute to the equilibrium besides the three open forms (2a-c) [29]. According to 1 H and 13 C NMR (J-MOD) measurements, only one of the possible tautomers (2d) is present in dimethyl sulfoxide (DMSO) solution in good agreement with previous studies, where the same form was evidenced by IR and XRD in the solid-state [23]. various cancerous and noncancerous lines, cells were seeded again in 5000 cells/well density in 96 well plates and treated with the compound in 1, 3, 5, 7, and 9 μM concentrations or cisplatin in 20, 40, 80, 160, and 330 nM concentrations for 72 h. After the treatments, cells were washed using phosphate-buffered saline (PBS) and incubated with 0.5 mg/mL MTT reagent (SERVA, GmbH, Heidelberg, Germany) diluted in respective cell culture media without fetal bovine serum (FBS) for 1 h at 37 °C.…”

Section: Synthetic Studiessupporting

confidence: 90%

Microwave-Assisted Synthesis, Proton Dissociation Processes, and Anticancer Evaluation of Novel D-Ring-Fused Steroidal 5-Amino-1-Arylpyrazoles

et al. 2019

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Taking into account the pharmacological relevance of heterocycle-fused natural steroids, the objective of the current study was to develop a multistep reaction sequence for the efficient synthesis of novel D-ring-condensed 5-amino-1-arylpyrazoles from dehydroepiandrosterone (DHEA). A condensation reaction of 16-formyl-DHEA with hydroxylamine afforded the corresponding oxime, which was demonstrated to be stable in one of its cyclic isoxazoline forms due to possible ring-chain tautomerism. The subsequent base-induced dehydration to a diastereomeric β-ketonitrile, followed by microwave-assisted heterocyclization with different arylhydrazines led to the desired pyrazoles. The generally good yields of the products depended slightly on the electronic character of the substituent present on the aromatic ring of the reagent. The proton dissociation processes of the DHEA-derived heterocycles were investigated in aqueous solution by UV-visible spectrophotometric titrations to reveal their actual chemical forms at physiological pH. The determined pKa values attributed to the pyrazole NH+ moiety were low (1.8–4.0) and varied by the different substituents of the benzene ring. The antiproliferative effects of the structurally similar compounds were screened in vitro on human cancer cells (namely on HeLa, U2Os, MCF-7, PC-3, and A549), along with a noncancerous cell line (MRC-5). The IC50 values of the most active derivative were determined on all cell lines.

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Section: Synthetic Studiessupporting

confidence: 90%

Microwave-Assisted Synthesis, Proton Dissociation Processes, and Anticancer Evaluation of Novel D-Ring-Fused Steroidal 5-Amino-1-Arylpyrazoles

et al. 2019

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“…Wir haben 4, mit N-Bromsuccinimid (oder Brom2)) in wasserigem Medium behandelt, wobei sich 3-Brommethyl-3fluor-4,4-dimethy1-2-pentanon (1, 85%) als einziges identifizierbares Produkt bildete. Das 2,3,4,4-Tetramethyl-l-penten-3-01 setzte sich gleichartig urn, wobei in ebenfalls nahezu vollstandiger Ausbeute 3-Brommethyl-3,4,4-trimethyl-2-pentanon (5, 88%) entstand.…”

Section: Discussionunclassified

“…Dazu taucht jetzt ein neuer, wichtiger Gesichtspunkt auf, weil sich Anlagerung und Umlagerung unzweifelhaft antiperiplanar vollziehen (vgl. [4]). Die Leichtigkeit, mit welcher das Bromenium-Ion auf der einen oder anderen Seite an die olefinische Doppelbindung herantreten kann, bestimmt nun ebenfalls daruber mit, welche Gruppe iibertragen werden soll.…”

Section: *)unclassified

“…Im Gegensatz d a m verlief die gleiche Reaktion mit 3,4,4-Trimethyl-l -penten-3-01 uneinheitlich. Es traten nebeneinander drei Produkte auf, namlich das l-Brom-2,4,4-trimethyl-3-pentanon (2, 12%), das 3-Brommethyl-4,4-dimethyl-2-pentanon (3, 58%) sowie das 3-Brommethyl-2-t-butyl-2-methyloxiran (4, 16%).Vorbilder fur die Umlagerung, die zum in /3-Stellung bromierten und in a-Stellung doppelt verzweigten Keton 5 fuhrt, finden sich in der Literatur [4] [ 5 ] . Dariiber hinaus ist die Umwandlung des 2-Phenyl-3-buten-2-01~, also eines tertiaren Allylalkohols mit unsubstituierter Vinylgruppe, zum 4-Brom-3-phenyl-2-butanon l)…”

unclassified

“…Vorbilder fur die Umlagerung, die zum in /3-Stellung bromierten und in a-Stellung doppelt verzweigten Keton 5 fuhrt, finden sich in der Literatur [4] [ 5 ] . Dariiber hinaus ist die Umwandlung des 2-Phenyl-3-buten-2-01~, also eines tertiaren Allylalkohols mit unsubstituierter Vinylgruppe, zum 4-Brom-3-phenyl-2-butanon l)…”

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Durch Bromierung ausgelöste Umlagerung tertiärer Allylalkohole: Der Einfluss eines Fluor‐Substituenten auf Reaktionsgeschwindigkeit und Reaktionsverlauf

Nagakura

Savary

Schlosser

1980

Helvetica Chimica Acta

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The ally1 alcohol bearing a methyl and a t-butyl group at the hydroxylated position was found to undergo a rearrangement when treated with bromine (or N-bromosuccinimide) in an aqueous medium and to afford a product mixture containing two regioisomeric ketones and one oxirane. Introduction of an additional methyl group or a fluorine atom at the non-terminal olefinic center led to a more selective discrimination between potential migratory groups. As the result of an exclusive t-butyl shift only one product, a ketone, was formed in both cases. Whereas the reaction rate was only slightly affected by the additional methyl group, it was substantially decreased by the fluorine atom.Wir haben 2-Fluor-3,4,4-trimethyl-l -penten-3-01 [2] mit N-Bromsuccinimid (oder Brom2)) in wasserigem Medium behandelt, wobei sich 3-Brommethyl-3fluor-4,4-dimethy1-2-pentanon (1, 85%) als einziges identifizierbares Produkt bildete. Das 2,3,4,4-Tetramethyl-l-penten-3-01 setzte sich gleichartig urn, wobei in ebenfalls nahezu vollstandiger Ausbeute 3-Brommethyl-3,4,4-trimethyl-2-pentanon (5, 88%) entstand. Im Gegensatz d a m verlief die gleiche Reaktion mit 3,4,4-Trimethyl-l -penten-3-01 uneinheitlich. Es traten nebeneinander drei Produkte auf, namlich das l-Brom-2,4,4-trimethyl-3-pentanon (2, 12%), das 3-Brommethyl-4,4-dimethyl-2-pentanon (3, 58%) sowie das 3-Brommethyl-2-t-butyl-2-methyloxiran (4, 16%).Vorbilder fur die Umlagerung, die zum in /3-Stellung bromierten und in a-Stellung doppelt verzweigten Keton 5 fuhrt, finden sich in der Literatur [4] [ 5 ] . Dariiber hinaus ist die Umwandlung des 2-Phenyl-3-buten-2-01~, also eines tertiaren Allylalkohols mit unsubstituierter Vinylgruppe, zum 4-Brom-3-phenyl-2-butanon l)

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Hydrocyanation of Conjugated Carbonyl Compounds

Nagata

Yoshioka

1977

Organic Reactions

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Hydrogen cyanide adds to a multiple bond in the presence of an appropriate catalyst. The process is called hydrocyanation. The addition to an α,β‐unsaturated carbonyl compound gives a 1,2 adduct, α‐cyanohydrin, and a 1,4 adduct, β‐cyano ketone. Both 1,2 and 1,4 additions are reversible in principle, but in the presence of a base the reverse 1,2 addition is much faster than the reverse 1,4 reaction, leading to the 1,4 adduct as a major (usually sole) product. In this sense conjugate hydrocyanation is a special case of the Michael reaction. Predominance of 1,2 or 1,4 addition depends on the substrate structure, the reagent, and the reaction conditions. In this chapter 1,2 addition is discussed only when necessary. This chapter deals chiefly with the 1,4 addition and, more generally, with conjugate addition including that on conjugated polyethylenic compounds giving 1,6 or more extended conjugated adducts. Carbonyl substrates include ketones, aldehydes, carboxylic acid derivatives, carbonitriles, and carboimines. Also included are β‐functionalized carbonyl compounds, and π‐allylpalladium complexes, that generate α,β‐unsaturated carbonyl compounds, under hydrocyanation conditions. Although hydrogen cyanide adds to α,β‐unsaturated compounds activated by other groups such as nitro and sulfone, these reactions are not considered in this chapter. The first example of 1,4 addition of hydrogen cyanide to α,β‐unsaturated carbonyl derivatives appeared more than a century ago, in 1873, when Claus prepared tricarballylic acid (1,2,3‐propanetricarboxylic acid) by heating an ethanolic solution of 2,3‐dichloropropene and potassium cyanide in a sealed tube. The discovery in 1903 that the reactive species in hydrocyanation is the cyanide anion, CN − , and that the rate of the reaction is proportional to the concentration of CN −8 , formed the foundation for active study of hydrocyanation chemistry. A fundamental procedure for conjugate hydrocyanation was developed which used 2 molar equivalents of potassium cyanide and 1 molar equivalent of acetic acid in aqueous alcohol. The reaction mode was clarified by Ingold and Michael in the 1930s. Many chemists began extensive application of the reaction to organic syntheses, and attempts were made to explore improved procedures with higher efficiency and fewer side reactions. Detailed reviews cover developments of conjugate hydrocyanations up to the 1950s. In recent years conjugate hydrocyanation has been used in total syntheses of complex natural products such as terpenes, steroids, and alkaloids. However, conventional procedures using hydrogen cyanide in the presence of a base or an alkali or alkaline‐earth metal cyanide were not efficient. Furthermore, the efficiency could not be improved without increasing side reactions. The difficulty was overcome in 1962 when methods using organoaluminum compounds were discovered by Nagata and co‐workers. They developed two new hydrocyanation methods, one involving a combination of hydrogen cyanide and an alkylaluminum and the other an alkylaluminum cyanide, both in an aprotic solvent. Applications of the new methods have led to total syntheses of complex natural products having a methyl, a functionalized methyl, or a carbon bridge at an angular position.

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Reaktionen an 16‐Methylen‐ und 16‐Hydroxymethylen‐17‐Keto‐steroiden

Cited by 25 publications

References 16 publications

Microwave-Assisted Synthesis, Proton Dissociation Processes, and Anticancer Evaluation of Novel D-Ring-Fused Steroidal 5-Amino-1-Arylpyrazoles

Microwave-Assisted Synthesis, Proton Dissociation Processes, and Anticancer Evaluation of Novel D-Ring-Fused Steroidal 5-Amino-1-Arylpyrazoles

Durch Bromierung ausgelöste Umlagerung tertiärer Allylalkohole: Der Einfluss eines Fluor‐Substituenten auf Reaktionsgeschwindigkeit und Reaktionsverlauf

Hydrocyanation of Conjugated Carbonyl Compounds

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