1156-86-1

Upstream product

• 481-29-8 Epiandrosterone 
• 10429-07-9 3β-tosyloxy-5α-androstan-17-one 
• 53-41-8 cis-androsterone 
• 19646-53-8 (3β,5α)-3-[(methylsulfonyl)oxy]androstan-17-one 

Relevant academic research and scientific papers

Chemical synthesis, NMR analysis and evaluation on a cancer xenograft model (HL-60) of the aminosteroid derivative RM-133

The aminosteroid derivative RM-133 has been reported to be a promising pro-apoptotic agent showing activity on various cancer cell lines. Following the development of solid-phase synthesis that generated a series of libraries of aminosteroid derivatives, we now report the development of a convenient liquid phase chemical synthesis of RM-133, the most promising candidate, in order to obtain sufficient quantities to proceed with the first preclinical assays. A simple and convergent six-step synthesis was designed and allowed the preparation of a gram-quantity scale of RM-133. This aminosteroid derivative was also fully characterized by NMR experiments which revealed an interesting mixture of conformers. Finally, the in vivo potency of RM-133 was evaluated on a xenograft model in nude mice with HL-60 tumors, which has resulted in the blocking of tumor progression by 57%.

PyFluor: A low-cost, stable, and selective deoxyfluorination reagent

We report an inexpensive, thermally stable deoxyfluorination reagent that fluorinates a broad range of alcohols without substantial formation of elimination side products. This combination of selectivity, safety, and economic viability enables deoxyfluorination on preparatory scale. We employ the [18F]-labeled reagent in the first example of a no-carrier-added deoxy-radiofluorination.

Rapid Deoxyfluorination of Alcohols with N-Tosyl-4-chlorobenzenesulfonimidoyl Fluoride (SulfoxFluor) at Room Temperature

The deoxyfluorination of alcohols is a fundamentally important approach to access alkyl fluorides, and thus the development of shelf-stable, easy-to-handle, fluorine-economical, and highly selective deoxyfluorination reagents is highly desired. This work describes the development of a crystalline compound, N-tosyl-4-chlorobenzenesulfonimidoyl fluoride (SulfoxFluor), as a novel deoxyfluorination reagent that possesses all of the aforementioned merits, which is rare in the arena of deoxyfluorination. Endowed by the multi-dimensional modulating ability of the sulfonimidoyl group, SulfoxFluor is superior to 2-pyridinesulfonyl fluoride (PyFluor) in fluorination rate, and is also superior to perfluorobutanesulfonyl fluoride (PBSF) in fluorine-economy. Its reaction with alcohols not only tolerates a wide range of functionalities including the more sterically hindered alcoholic hydroxyl groups, but also exhibits high fluorination/elimination selectivity. Because SulfoxFluor can be easily prepared from inexpensive materials and can be safely handled without special techniques, it promises to serve as a practical deoxyfluorination reagent for the synthesis of various alkyl fluorides.

Synthesis of fluorinated steroids using a novel fluorinating reagent tetrabutylammonium difluorodimethylphenylsilicate (TAMPS)

Steroidal 3-fluoroderivatives were prepared from corresponding tosylates using tetrabutyl-ammonium difluorodimethylphenylsilicate as fluorinating agent. The reaction was tested on all four possible C-3 and C-5 stereoisomers of cholestane and 17-oxoandrostane skeletons. In this reaction only one isomer was always formed with opposite configuration at C-3 to starting tosylate. The reaction is accompanied by elimination which affords a mixture of corresponding olefines.

Preparation of 3,17- and 3,20-difluoro-derivatives of the androst-5-ene and pregn-5-ene series

Unsaturated mono- and difluorosteroids have been prepared in high yield using n-perfluorobutanesulfonyl fluoride 1. The 3,17- and 3,20-difluoro-5,6- dehydrosteroids are reported for the first time. 3-Fluoroderivatives of the androst-5-ene-17-one and 5α-an

Fluorination of secondary and primary alcohols by thermal decomposition of electrochemically generated alkoxy triphenylphosphonium tetrafluoroborates

Replacement of hydroxyl groups in secondary and primary alcohols (1) with a fluorine atom arising from tetrafluoroborate anion has been performed by the electrochemical formation of alkoxy triphenylphosphonium tetrafluoroborates (2) from 1, followed by their thermal decomposition. The procedure is quite simple, involving: (1) constant-current electrolysis of a mixture of 1, Ph3P, and Ph3PH·BF4 in CH2Cl2 in an undivided cell; (2) refluxing a tetrahydrofuran or dioxane solution of the residue afforded by evaporation of the solvent in vacuo after the electrolysis. Cyclic secondary alcohols such as 3β-hydroxy steroids and 2-adamantanol are transformed into the corresponding fluorides in satisfactory yields when the geometry of the leaving group in 2 is suitable for the substitution or an elimination process for 2 to give an alkene is stereochemically forbidden. The fluorination of steroidal alcohols and 4-phenyl-1-cyclohexanol proceeded with complete inversion, demonstrating that a fluorine atom from the tetrafluoroborate anion attacks from the side opposite to the phosphonium moiety in 2 via an SN2 mechanism rather than an SN1 mechanism. The fluorination of acyclic secondary and primary alcohols was performed by the present method in reasonable yields, although the reaction for the latter required more forcing conditions, such as refluxing in dioxane.

Facile Preparation of Tetrabutylphosphonium Fluoride and Its HF Adducts. New Fluoride Anion Sources for Selective Nucleophilic Fluorination

Anhydrous tetrabutylphosphonium hydrogen bifluoride (2), dihydrogen trifluoride prepared from aq. tetrabutylphosphonium hydroxide and aq.HF, and tetrabutylphosphonium fluoride prepared from 2 and BunLi were shown to be useful fluoride sources for selective nucleophilic fluorination of oxiranes, alkyl halides, alcohols and sulfonates of aliphatic and steroidal species.

1H NMR Analyses, Shielding Mechanisms, Coupling Constants, and Comformations is Steroids Bearing Halogen, Hydroxy, Oxo Groups, and Double Bonds

The 1H NMR analyses of 16 5αH-androstanes and one progesterone analogue furnish shifts and coupling constants for the basic steroid skeleton and substituent-induced shifts (SIS) for oxo, hydroxy, and halogen groups as well as for a Δ double bond.It is shown how a single 2D experiment complemented by a NOE difference spectrum can lead to complete assignments even with the most complicated spin systems compirising, e.g., 29 strongly coupled protons within only 1 ppm; the accurancy of information from 2D techniques is evaluated by comparison to some 1D and computer-simulated spectra.On the basis of up to six simultaneously observable couplings, a special approach is used to scan the conformational space of particularly flexible parts.Intermediate conformations between half-chair and twist are obtained with a torsional C14-C15-C16-C17 angle of φ ca. 20 deg for the D ring with a sp2 (17-oxo) carbon and of φ ca. 10 deg with only sp3 carbon atoms; the observed flat profiles, however, allow also for mixtures of different conformations, which is supported by MM2 calculations.For the Δ-3-oxo A ring, a sofa conformation is favored compared to a half-chair geometry.The observed shielding effects of heterosubstituents are partially at variance with the few earlier observations, which were mostly based on polysubstituted compounds.Classical shielding mechanisms were evaluated with the program SHIFT, based on force-field-minimized structures.Steric-induced shielding dominates in the hydrocarbon, leading to upfield shifts increasing with the number of 1,3-diaxial interactions.Linear electric-field effects predict, e.g., the shielding difference between equatorial and axial protons vicinal to C-Hal bonds and the deshielding observed for diaxial C-Hal/C-H bond arrangements.A combination of anisotropy and electric-field effects explains all shifts observed in the ketones with the exception of protons vicinal to C=O; a multilinear regression analysis leads to Δχ1C=O = -36 (-27) and Δχ2C=O = -24 (-21) (10-3 cm3/molecule, old ApSimon values in parentheses); it is, however, demonstrated, that an analysis on the basis of NMR shifts alone leads to broad ranges of parameters.Parallels between 1H and 13C NMR shifts are drawn, particularly at γ and θ positions to C-Hal bonds.