Angel Mendoza

Novel synthesis of steroidal oximes and lactams and their biological evaluation as antiproliferative agents

HIGHLIGHTSTwo novel and short methods to introduce the hydroxyimino group at C‐6 on the steroidal skeleton are described.An efficient route to obtain B‐homolactams in just three steps from the natural steroids is presented.The antiproliferative activity of the new steroidal oximes and lactams was evaluated. ABSTRACT A novel three‐step methodology to obtain 6a‐aza‐B‐homo steroidal lactams has been developed starting from the easily available cholesterol and pregnenolone. In addition, a new procedure for the synthesis of a 6a‐aza‐B‐homo steroidal lactam analog of vespertilin, starting from diosgenin has been established. In both synthetic pathways, the key intermediate is a hydroxyimino derivative obtained in a one‐ or two‐step sequence from the starting materials. These methods avoid the use of hazardous oxidant agents in the process. The new steroidal oximes and lactams were examined for their antiproliferative activities against several tumor cell lines. The 6,23‐dihydroxyimino derivative exhibited the highest activity with GI50 values of 11–22 &mgr;M.

(E)-1-(4-Nitro-benzyl-idene)-2,2-diphenyl-hydrazine.

The asymmetric unit of the title compound, C19H15N3O2, contains two molecules, both of which show an E conformation of the imine bond. The dihedral angles between the phenyl rings in the phenylhydrazine groups are 86.09 (6) and 83.41 (5)° in the two molecules. The 4-nitrobenzene rings show torsion angles of 4.4 (2) and 10.9 (2)° from the two C=N—N planes. In the crystal, C—H⋯π interactions and C—H⋯O hydrogen bonds are observed growing along the a, b and c axes, resulting in a complex supramolecular array.

Diastereoselective Approach to cis-4-Methyl/thiol-Pipecolic Esters Based on RCM Reaction and Conjugate Michael Addition

Abstract A synthetic route for the access to enantiopure cis-4-methyl/thiol-pipecolic esters is presented. It is based on the ring-closing metathesis reaction to build the α,β-unsaturated piperidin-2-one derived from (S)-(–)-phenylethylamine, followed by either diastereoselective conjugate addition of methylorganocuprate allowing access to cis-4-methyl pipecolic ester or by tandem diastereoselective hydrosulforization–thionization reaction providing access to cis-4-thiol pipecolic ethyl esters. GRAPHICAL ABSTRACT

(E)-1-Benzyl-idene-2,2-diphenyl-hydrazine.

The asymmetric unit of the title compound, C19H16N2, contains two independent molecules, both of which show an E configuration with respect to the C=N bond. The dihedral angles between the phenyl rings bonded to the hydrazine group are 81.00 (10) and 88.34 (8)° in the two molecules. Intermolecular C—H⋯π interactions are observed in the crystal structure.

2,5-Bis{[(−)-(S)-1-(4-bromo­phen­yl)eth­yl]imino­meth­yl}thio­phene

The title compound, C22H20Br2N2S, was synthesized under solvent-free conditions. The molecule shows crystallographic C 2 symmetry, with the S atom of the central thiophene ring lying on a twofold rotation axis. Furthermore, as a consequence of the (S,S) stereochemistry, the molecule has a twisted conformation. The dihedral angle between the thiophene and benzene rings is 72.7 (2)° and that between the two benzene rings is 55.9 (2)°. In the crystal, molecules are arranged in a chevron-like pattern, without any significant intermolecular interactions.

2,2-Dimethyl-5-(2-nitro­benzyl­idene)-1,3-dioxane-4,6-dione

The asymmetric unit of the title compound, C13H11NO6, contains two molecules in both of which the six-membered 1,3-dioxane-4,6-dione ring shows a screw-boat conformation. The dihedral angles between the best planes through the six-membered rings are 47.8 (2) and 49.8 (2)°. In the crystal, C—H⋯O interactions link the molecules, building a supramolecular sheet parallel to the c axis.

N′-[5-(4-Nitro­phen­yl)furan-2-yl­methyl­idene]-N,N-diphenyl­hydrazine

The title compound, C23H17N3O3, has an E configuration with respect to the C=N bond. The dihedral angle between the two phenyl rings bonded to the hydrazine group is 86.45 (13)°. The furan ring makes dihedral angles of 3.4 (2) and 7.06 (13)°, respectively, with the methylidenehydrazine C=N—N plane and the benzene ring.

(1E,2E)-1,2-Bis(2,2-diphenyl­hydrazin-1-yl­idene)ethane

In the crystal structure of the title compound, C26H22N4, the molecule is located on an inversion centre and shows an E configuration with respect to each C=N bond. The dihedral angle between the phenyl rings in the diphenylhydrazone group is 83.69 (11)°. These two rings make dihedral angles of 30.53 (15) and 84.53 (16)° with the central N—N=C—C=N—N dihydrazonoethane plane. Intermolecular C—H⋯π interactions are observed.

Crystal structure of r-1,c-2-dibenzoyl-t-3,t-4-bis­(2-nitro­phen­yl)cyclo­butane

The title molecule is a tetrasubstituted truxinic-type cyclobutane derivative with a central ring that is almost planar despite of being placed in a general position. The molecular structure of the dimer shows that the four benzene rings of the substituents are oriented in such a way that potential steric hindrance is minimized, whilst allowing some degree of intermolecular π–π interactions for crystal stabilization.

CCDC 1439218: Experimental Crystal Structure Determination

Related Article: Estibaliz Sansinenea, Francisco Salazar, Jacqueline Jimenez, Angel Mendoza, Aurelio Ortiz|2016|Tetrahedron Lett.|57|2604|doi:10.1016/j.tetlet.2016.04.117