(E)-(25S)-23-Acetyl-5β-furost-22-ene-3β,26-diol

The title steroid, C29H46O4, is a furostene derivative with a C=C double-bond length of 1.353 (3) Å and an E configuration. The side chain is oriented toward the α face of the A–E steroidal nucleus and presents a disordered terminal CH2—OH group [occupancies for resolved sites are 0.591 (9) and 0.409 (9)]. The methyl group at C20 attached to ring E is also oriented toward the α face, avoiding steric hindrance with the carbonyl O atom of the acetyl group. The furostene and acetyl functionalities form an α,β-unsaturated ketone system, with an s-cis configuration. All hydr­oxy and carbonyl groups are involved in weak inter­molecular hydrogen bonds. The absolute configuration was assigned from the synthesis

Westphalen's diol diacetate: 19(10→5)-abeo-5β-cholest-9-ene-3β,6β-diyl diacetate

The structure of the title steroid [alternative name: 3,6- diacetoxy-5-methyl-19-norcholest-9(10)-ene], C31H50O4, confirms the generally accepted mechanism for the rearrangement of a cholestan-5�-ol derivative reported a century ago by Westphalen. The methyl group at position 10 of the starting material migrates to position 5 in the steroidal nucleus, while a 9 bond is formed, as indicated by the C C bond length of 1.347 (4)

The zwitterion (23′E)-(23R,25S)-23-[1-(oxidoiminio)eth­yl]-5β-spiro­stan-3β-yl acetate

The title steroidal compound, C31H49NO5, resulted from the selective oximation of (23R)-23-acetyl­sarsasapogenin acetate. One- and two-dimensional 1H and 13C NMR spectra, as well as IR data, are in agreement with the presence of a ketoxime group at C-23. However, recrystallization in slightly acidic media affords the title compound in the rare zwitterionic oxime form, as a consequence of migration of the hydr­oxy H atom to the N atom in the oxime group. This H atom is clearly detected and its position was refined from X-ray data. The geometry for the C=N+(H)—O− group features long C=N and short N—O bond lengths compared to non-zwitterionic oximes. The ketoxime is stabilized with the E configuration, avoiding steric hindrance between the oxime O atom and H atom at C-23. The sum of the angles around the oxime N atom is 359.6°, giving a planar configuration for that atom, as expected for sp 2 hybridization

(20S,2′′S)-20-[4′-(3′′-Hydroxy-2′′-methyl­prop­yl)-3′-methylisoxazol-5-yl]-5β-preg­nan-3β,16β-diol

The title steroidal compound, C29H47NO4, was prepared in a one-pot reaction starting from a sarsasapogenin derivative of known configuration. The isoxazole heterocycle is oriented towards the α face of the steroid nucleus and, although fully functionalized on C atoms, does not provoke steric hindrance with the adjacent D ring. The absolute configuration observed for chiral centers is as expected, and shows that no epimerization occurred in the precursors. In the crystal, the three OH groups serve as donors for hydrogen bonding with O and N atoms. The isoxazole N atom is involved in O—H⋯N hydrogen bonds, forming chains along [100]. These chains are further connected via O—H⋯O and weak C—H⋯O contacts, giving rise to a three-dimensional supra­molecular network

3-tert-Butyl 5-methyl (2R,4S,5R)-2-(4-methoxyphenyl)-4-(3-nitrophenyl)-1,3-oxazolidine-3,5-dicarboxylate

The title mol­ecule, C(23)H(26)N(2)O(8), was synthesized in three steps starting from m-nitro­cinnamic acid. The central oxazolidine ring adopts an almost perfect envelope conformation with the O atom as the flap [puckering parameter ϕ = 0.3 (6)°]. The dihedral angle formed by the benzene rings is 61.81 (9)°. In the crystal, mol­ecules are connected into double chains parallel to [010] by C—H⋯O hydrogen bonds. The absolute configuration was assigned from the synthetic procedure

Accurate stereochemistry for two related 22,26-epimino­cholestene derivatives

Regioselective opening of ring E of solasodine under various conditions afforded (25R)-22,26-epimino­cholesta-5,22(N)-di­ene-3β,16β-diyl diacetate (previously known as 3,16-diacetyl pseudosolasodine B), C31H47NO4, or (22S,25R)-16β-hydr­oxy-22,26-epimino­cholesta-5-en-3β-yl acetate (a derivative of the naturally occurring alkaloid oblonginine), C29H47NO3. In both cases, the reactions are carried out with retention of chirality at the C16, C20 and C25 stereogenic centers, which are found to be S, S and R, respectively. Although pseudosolasodine was synthesized 50 years ago, these accurate assignments clarify some controversial points about the actual stereochemistry for these alkaloids. This is of particular importance in the case of oblonginine, since this compound is currently under consideration for the treatment of aphasia arising from apoplexy; the present study defines a diastereoisomerically pure compound for pharmacological studies

2-Aminobenzoxazole-appended coumarins as potent and selective inhibitors of tumour-associated carbonic anhydrases

We have carried out the design, synthesis, and evaluation of a small library of 2-aminobenzoxazole-appended coumarins as novel inhibitors of tumour-related CAs IX and XII. Substituents on C-3 and/or C-4 positions of the coumarin scaffold, and on the benzoxazole moiety, together with the length of the linker connecting both units were modified to obtain useful structure-activity relationships. CA inhibition studies revealed a good selectivity towards tumour-associated CAs IX and XII (Ki within the mid-nanomolar range in most of the cases) in comparison with CAs I, II, IV, and VII (Ki > 10 µM); CA IX was found to be slightly more sensitive towards structural changes. Docking calculations suggested that the coumarin scaffold might act as a prodrug, binding to the CAs in its hydrolysed form, which is in turn obtained due to the esterase activity of CAs. An increase of the tether length and of the substituents steric hindrance was found to be detrimental to in vitro antiproliferative activities. Incorporation of a chlorine atom on C-3 of the coumarin moiety achieved the strongest antiproliferative agent, with activities within the low micromolar range for the panel of tumour cell lines tested.España MICINN (PID2020-116460RB-I00, PGC2018- 094503-B-C22)Junta de Andalucía (FQM134)Gobierno de Canarias ProID202001010

Propuesta estratégica de mejora en la implementación de los estándares mínimos del sistema de gestión de la seguridad y salud en el trabajo (SG-SST) en la empresa Transcarga Berlinas S.A. para el primer semestre del 2019.

Análisis de resultados en una matriz de estándares mínimos del SG-SST, para proponer estrategia de mejora luego de identificar las acciones que se requiere reforzar sobre los estándares mínimos que obtuvieron calificaciones bajas.Analysis of results in a matrix of SG-SST standards, for the improvement strategy to identify the actions that are required