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.     

19F-Labeled Probes for Recognition-Enabled Chromatographic 19F NMR

The NMR technique is among the most powerful analytical methods for molecular structural elucidation, process monitoring, and mechanistic investigations; however, the direct analysis of complex real-world samples is often hampered by crowded NMR spectra that are difficult to interpret. The combination of fluorine chemistry and supramolecular interactions leads to a unique detection method named recognition-enabled chromatographic (REC) ¹⁹F NMR, where interactions between analytes and ¹⁹F-labeled probes are transduced into chromatogram-like ¹⁹F NMR signals of discrete chemical shifts. In this account, we summarize our endeavor to develop novel ¹⁹F-labeled probes tailored for separation-free multicomponent analysis. The strategies to achieve chiral discrimination, sensitivity enhancement, and automated analyte identification will be covered. The account will also provide a detailed discussion of the underlying principles for the design of molecular probes for REC ¹⁹F NMR where appropriate.     

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 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 6,19-epoxide, the selective hydrolysis of the free -acetoxy group, the conversion of the 3-hydroxy-5-bromo derivative into the ⁴-3-ketone, and the reductive cleavage of the 6,19-epoxide ring.Institute of Bioorganic Chemistry, Belorussian Academy of Sciences, Minsk. Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 672–678, 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.     

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-Nor-steroids V. New synthesis of 6-dehydro-19-nor-steroids

A new efficient approach to the synthesis of Δ^4,6-3-oxo-19-norsteroids is described. Starting from 3β, 17α-diacyloxy-20-oxo-Δ⁵-pregnenes, the derivatives VIIIa and VIIIb of 6-dehydro-19-norprogesterone have been synthesized, which exhibit high progestational activity. Modification of the procedure leads to the new group of steroidal Δ^5(10),6-dienes.     

10-chloro-19-norcardiosteroids

Substitution of the angular aldehyde by halogen in cardiosteroids in two steps was studied. The first step was oxidation of the aldehyde and production of the cooresponding 19-carboxylic acids; the second, decarboxylation of the 19-carboxylic acids using N-chlorosuccinimide or chloride salts. The 10-chloro-19norcardiosteroids: 10-chloro-19-norstrophanthidine (1), 10-chloro-19-norcymarin (2), 10-chloro-19norconvallatoxin (3), 10-chloro-19-norstrophalloside (4), and 10-chloro-19-norbovoside A (5) were prepared for the first time. The intermediates strophalloside-19-carboxylic acid and bovoside A-19-carboxylic acid were also prepared for the first time and characterized.     

19F-Kernresonanzuntersuchungen an Imidoschwefeloxiddifluoriden

¹⁹F nuclear magnetic resonance studies on imidosulphuroxide difluorides Non equivalent fluorine atoms bounded to hexavalent sulphur of the NSOF₂ group in thionyl compounds give extreme AB-spectra.