Synthesis of 19-hydroxysteroids I. New synthesis of 19-hydroxytestosterone

For obtaining 19-hydroxytestosterone from dehydroepiandrosterone a new scheme of synthesis has been developed the key stages of which are the reduction of the 17-keto group to a 17-alcohol, the functionalization of the 19-methyl group via the bromohydrin with the formation of a 6β,19-epoxide, the selective hydrolysis of the free β-acetoxy group, the conversion of the 3β-hydroxy-5α-bromo derivative into the Δ⁴-3-ketone, and the reductive cleavage of the 6β,19-epoxide ring.     

19-O-Acetylchaetoglobosin B and 19-O-Acetylchaetoglobosin D,Two New Metabolites of Chaetomium globosum

Two new metabolites have been isolated from cultures of Chaetomium globosum. The structures of 19-O-acetylchaetoglobosin B ( 4 ) and 19-O-acetylchaetoglobosin D ( 5 ) are assigned. The ¹³C-NMR. spectra of chaetoglobosin A ( 1 ), 19-O-acetylchaetoglobosin A ( 2 ), chaetoglobosin C ( 3 ), 19-O-acetylchaetoglobosin B ( 4 ), 19-O-acetylchaetoglobosin D ( 5 ) and of cytochalasin G ( 6 ), a (3-indolyl)-[11]cytochalasan isolated from Pseudeurotium zonatum, have been interpreted.     

Some transformations of 19-oxygen-containing steroids

Chemistry of Natural Compounds - The influence of the activity of the zinc dust on the reductive cleavage of the oxide ring of 6β,19-epoxysteroids has been studied. An unusual ease of...     

Synthesis of 19-hydroxysteroids II. New synthesis of 19-hydroxyprogesterone

19-Hydroxyprogesterone has been synthesized in seven stages from pregnenolone with an overall yield of 11%.Institute of Bioorganic Chemistry, Belorussian Academy of Sciences, Minsk. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 678–682, November–December, 1992.     

Synthesis of 19-hydroxysteroids II. New synthesis of 19-hydroxyprogesterone

19-Hydroxyprogesterone has been synthesized in seven stages from pregnenolone with an overall yield of 11%. Institute of Bioorganic Chemistry, Belorussian Academy of Sciences, Minsk. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 678–682, November–December, 1992.     

19-Norcardenolides

The products of the autooxidation of the cardenolides strophanthidin and erysimin in solutions have been studied. It has been established that the autooxidation of 19-oxocardenolides forms, together with 19-carboxylic acids, a complex mixture of 19-norcardenolides. The bulk of them consists of 10-OH compounds and a smaller proportion of 10-H compounds. Autooxidation affects both the functional group at C-10 and its transformation and also other groupings and bonds in ring A and, to some extent, in ring B, including the oxidation of the 3-OH group, degradation of the 5-OH group, and cleavage of the C₅-C₁₀ bond with the formation of 5,10-seco-19-norcardenolides. A possible mechanism of the formation of 19- norcardenolides is discussed.All-Union Scientific-Research Institute of Drug Chemistry and Technology, Khar'kov. Translated from Khimiya Prirodnykh Soedinenii, No. 1, pp. 71–76, January–February, 1985.     

Investigation of steroids. XLII. Transformation of 17-alpha-pseudostrophanthidins to 19-hydroxy-8,19-epoxy-14-beta,17-alpha-cortexone and 8-hydroxy-19-nor-14-beta,17-alpha-cortexone

The synthesis of a structural isomer of aldosterone, viz. 19-hydroxy-8, 19-epoxy-(11-) de(s)oxycorticosterone (= 19-hydroxy-8, 19-epoxy-cortexone), and a number of related compounds was reported earlier from this laboratory [1]. It appeared desirable to prepare the corresponding compounds of the 17α-series also, such as 19-hydroxy-8, 19-epoxy-14 β, 17 (βH)-deoxycorticosterone ( 28 ). 17 α-Pseudostrophanthidin ( 2 ), which has not yet been described in the literature, was considered as starting material for the synthesis of 28. 2 has now been prepared by heating a solution of pseudostrophanthidin ( 1 ) in dimethylformamide in the presence of sodium p-toluenesulfonate and anhydrous sodium acetate. 2 was characterized as the 3, 19-diacetate ( 7 ), the 19-methylal ( 8 ) and the 3-monoacetat ( 9 ). 9 was also obtained by acetylating the methylal 8 and demethylating the resulting reaction product 10. To support the structures assigned to 9 and, by implication, to 2 , a series of further reactions were carried out.     

Convenient preparative routes to 19-hydroxy, 19-oxo-, 19-oic-, and 19-nor-deoxycorticosterone

Practical synthetic routes to 19-hydroxy-, 19-OXO-, 19-oic-, and 19-nor-deoxy-corticosterone were developed. 19-Hydroxydeoxycorticosterone (11) and its 21-acetate 10 were first prepared by two routes via O-protected 19-oxygenated intermediates 6 and 17 starting from readily available pregnenolone acetate (1) and dehydroepiandrosterone acetate (12). The key step in the first route is the application of Henbest acetoxylation at C-21 to the enamine 7 derived from 6. The second route involves introduction of a hydroxyacetyl side chain at C-17 starting with base-catalyzed condensation of 17 with methoxyacetic ester. 19-Oxo- and 19-oic-deoxycorticosterone (23 and 25) and their 21-acetates 22 and 24 were obtained via chromium trioxide oxidation of 10 under different controlled conditions. Alkaline hydrolysis of 22 under decarbonylation led to 19-nor-deoxycorticosterone(26). Alternatively, a short-step synthesis of the latter steroid from estrone methyl ether (27) was achieved by utilizing the same procedure for construction of the corticoid side chain.     

Nigella sativa L. and COVID-19: A Glance at The Anti-COVID-19 Chemical Constituents,Clinical Trials,Inventions, and Patent Literature

COVID-19 has had an impact on human quality of life and economics. Scientists have been identifying remedies for its prevention and treatment from all possible sources, including plants. Nigella sativa L. (NS) is an important medicinal plant of Islamic value. This review highlights the anti-COVID-19 potential, clinical trials, inventions, and patent literature related to NS and its major chemical constituents, like thymoquinone. The literature was collected from different databases, including Pubmed, Espacenet, and Patentscope. The literature supports the efficacy of NS, NS oil (NSO), and its chemical constituents against COVID-19. The clinical data imply that NS and NSO can prevent and treat COVID-19 patients with a faster recovery rate. Several inventions comprising NS and NSO have been claimed in patent applications to prevent/treat COVID-19. The patent literature cites NS as an immunomodulator, antioxidant, anti-inflammatory, a source of anti-SARS-CoV-2 compounds, and a plant having protective effects on the lungs. The available facts indicate that NS, NSO, and its various compositions have all the attributes to be used as a promising remedy to prevent, manage, and treat COVID-19 among high-risk people as well as for the therapy of COVID-19 patients of all age groups as a monotherapy or a combination therapy. Many compositions of NS in combination with countless medicinal herbs and medicines are still unexplored. Accordingly, the authors foresee a bright scope in developing NS-based anti-COVID-19 composition for clinical use in the future.     

19F NMR study of fluorinated mono- and diacylhydrazines

Conclusions It has been demonstrated by means of¹⁹F NMR that l-acyl-2-alkyl (phenyl) hydrazines are the main products of the monoacylation of alkyl- and phenylhydrazine with derivatives of perfluorocarboxylic acids. The preferred conformations with respect to the amide bond have been determined in mono- and di (perfluoroacyl) hydrazines.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 12, pp. 2735–2739, December, 1980.     

Structure and absolute stereochemistry of 19-epi-(+)-echitoveniline : A new indole alkaloid of the leaves of Alstonia venenata r.br.

19-Epi-(+)-echitoveniline, a new indole alkaloid of the leaves ofAlstonia venenata R.Br., has been shown to possess the structure and absolute stereochemistry represented by 5b on the basis of spectral and chemical evidence. A mechanistic rationale for the dependence of the mode of LAH reduction of the δ-lactone 11 on its configuration at C-19 has been offered. The influence of the C-19 configuration on the chemical shift values of the C-16 carbomethoxy protons in the 19-aroyloxy-(+)-and (?)-vincadifformine alkaloids has been discussed.     

Synthesis and molecular docking study of novel COVID-19 inhibitors

In 2020, the world tried to combat the corona virus (COVID-19) pandemic. A proven treatment method specific to Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is still not found. In this study, seven new antiviral compounds were designed for COVID-19 treatment. The ability of these compounds to inhibit COVID-19’s RNA processing was calculated by the molecular docking study. It has been observed that the compounds can have high binding affinities especially against NSP12 (between -9.06 and -8.00 kcal/mol). The molecular dynamics simulation of NSP12-ZG 7 complex proved the stability of interaction. The synthesis of two most active molecules was performed by one-pot reaction and characterized by FT-IR, ¹H-NMR, ¹³C-NMR, and mass spectroscopy. The compounds presented with their synthesis are inhibitory core structures against SARS-CoV-2 infection.     

REACTION OF METHANE WITH CARBON DIOXIDE OVER SrNiAl_(11)O_(19)

合成了六铝酸盐ＳｒＮｉＡｌ１１Ｏ１９并用ＸＲＤ、ＵＶＤＲＳ、ＴＧＤＴＡ和ＴＥＭ等技术对其进行了表征。在７５０℃于ＳｒＮｉＡｌ１１Ｏ１９上进行的甲烷与二氧化碳重整反应表明，这类催化剂较Ｎｉ／ＳｒＡｌ１２Ｏ１９具有较大活性和低积碳能力，在催化反应过程中可有效地抑制Ｎｉ颗粒的增大。     

Surface-enhanced Raman spectra of rhodamine 19 octadecylamide

Surface-enhanced Raman scattering (SERS) of the cationic and the neutral form of rhodamine 19 octadecylamide (R19OA) has been studied in the silver citrate colloid using NIR excitation at 1064 nm. Cationic molecules readily adsorb onto negatively charged silver nanoparticles through a positively charged xanthene part of the molecules resulting in surface enhancement of Raman scattering. Due to a lack of the positive charge in molecular structure, SERS spectrum of neutral molecules is not observed. Nevertheless, a broad band appearing at 1240 cm^?1 in the spectrum of the cationic form indicates conversion of the cationic into the neutral species occurring close to the silver surface. The observed band most likely arises from a vibration of the ring formed in the molecular structure after conversion, but before complete desorption of the neutral molecules from the metal surface. Upon addition of HCl and NaOH in the silver sol, equilibrium is shifted toward the cationic and the neutral form of R19OA, respectively, followed by corresponding changes in the Raman spectrum. In addition, FT-SERS spectra of two rhodamine dyes, rhodamine 19 (R19) and rhodamine 6G (R6G), that are structurally related to R19OA, have been studied under the same experimental conditions for comparison.     

On-line TDPAC studies with the 19O beam

A new ¹⁹F probe disintegrated from short-lived ¹⁹O has been developed for the first time for time-differential perturbed angular correlation method. The angular correlation coefficient for the relevant cascade has been experimentally estimated to be A₂₂ = -0.17±0.01. As the first application of this technique to condensed matter physics, the probe was implanted in polycrystalline fullerene C₆₀. We have observed two contrastive perturbations acting on the probe nuclei, which reflect electrostatic and dynamic interactions with the extranuclear field.     

Stereocontrolled synthesis of gibberellin A19 from gibberellic acid

The biosynthetically important C-20 gibberellin, gibberellin A₁₉5, has been prepared from the readily obtained C-19 gibberellin, gibberellic acid 8, by means of an efficient stereocontrolled ten step sequence.     

Fluorine-19 nuclear magnetic resonance and biochemical characterization of fluorotyrosine-labeled-thymidylate-synthetase

Fluorotyrosine has been incorporated into thymidylate synthetase from Lactobacillus casei by growth of the bacterium in media containing 3-fluorotyrosine. The enzyme exhibited a specific activity 70% of that of the normal enzyme and formed a covalent binary complex with pyrimidine nucleotides, as well as a covalent ternary complex with 5-fluorodeoxyuridylate and 5,10-methylenetetrahydrofolate. ¹⁹F nuclear magnetic resonance spectroscopy has been used to follow the formation of these complexes. 5-Fluorodeoxyuridylate, dUMP, dTMP and dCMP produced identical conformational changes in the enzyme as monitored by the fluorotyrosyl resonances. Ternary complex formation of the fluorotyrosine-containing enzyme with 5-fluorodeoxyuridylate and 5,10-methylenetetrahydrofolate resulted in further spectral changes.     

Portable chemiluminescence multiplex biosensor for quantitative detection of three B19 DNA genotypes

A miniaturized multiplex biosensor exploiting a microfluidic oligonucleotide array and chemiluminescence (CL) lensless imaging detection has been developed for parvovirus B19 genotyping. The portable device consists of a reaction chip, comprising a glass slide arrayed with three B19 genotype-specific probes and coupled with a polydimethylsiloxane microfluidic layer, and a charge-coupled device camera modified for lensless CL imaging. Immobilized probes were used in DNA hybridization reactions with biotin-labeled targets, and then hybrids were measured by means of an avidin-horseradish peroxidase (HRP) conjugate and CL detection. All hybridization assay procedures have been optimized to be performed at room temperature through the microfluidic elements of the reaction chip, with sample and reagents delivery via capillary force exploiting adsorbent pads to drive fluids along the microchannels. The biosensor enabled multiplex detection of all B19 genotypes, with detectability down to 80 pmol?L^?1 for all B19 genotype oligonucleotides and 650 pmol?L^?1 for the amplified product of B19 genotype 1, which is comparable with that obtained in traditional PCR-ELISA formats and with notably shorter assay time (30 min vs. 2 h). The specificity of the assay has been evaluated by performing DNA–DNA hybridization reactions among sequences with different degrees of homology, and no cross hybridizations among B19 genotypes have been observed. The clinical applicability has been demonstrated by assaying amplified products obtained from B19 reference serum samples, with results completely consistent with the reference PCR-ELISA method. The next crucial step will be integration in the biosensor of a miniaturized PCR system for DNA amplification and for heat treatment of amplified products.

Electrochemically Enabled One-Pot Multistep Synthesis of C19 Androgen Steroids

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.