ABSTRACT
Four hybrid steroid dimers were obtained by BF3·Et2O-catalyzed aldol condensation of acetylated steroid sapogenins with 2-formyl-estradiol diacetate. The structures of the obtained dimers were unambiguously established by NMR. The hybrid dimers 9a (IC50 18.37⯵M) and 9c (IC50 9.4⯵M) with the 5α configuration at the A/B rings junction showed the higher cytotoxicity against HeLa, with selectivity index of 4.36 and 11.8 respectively. The presence of a carbonyl function at position C-12 produced the highest cytotoxic effect, which is in line with our previous reports.
ABSTRACT
23E-diacetoxybenzylidenespirostanes underwent rearrangement when treated with HCl in CH2Cl2/CH3OH. The course of the rearrangement depends on the substitution pattern in the phenyl ring. While compounds bearing an acetoxy group at the ortho position produced spirochromenes, the partners with no substituent at the ortho position led to spiroindenes. All the rearranged compounds exhibited moderate antioxidant activity.
Subject(s)
Acetals , Antioxidants , CatalysisABSTRACT
NaBH3CN reduction of symmetric dimers in which two steroid units are linked by a 1,4-dimethylidenebenzene moiety followed two different courses: (a) hydrogenation of the benzylic double bond and (b) reductive F ring opening of the side chain. While courses a and b led to symmetrical dimers, the combination of both pathways produced an unsymmetrical dimer that bears different side chains in each half. The exhaustive NMR characterization of all obtained compounds is presented.
Subject(s)
Steroids/chemistry , Dimerization , Molecular Conformation , Oxidation-Reduction , StereoisomerismABSTRACT
A novel stable donor/acceptor-supported MnI -metallasilanone 3 was synthesized. The intramolecular silanone-MnI interaction induces a highly strained three-membered cyclic structure, leading to an exceptionally high reactivity of 3 as a donor/acceptor complex of silanone. Indeed, metallasilanone 3 readily reacts with various small molecules such as H2 or ethylene gas in mild conditions.
ABSTRACT
A study of the reactivity of 25R and 25S 23E-benzylidene spirostanes that includes epoxidation, catalytic hydrogenation as well as Lewis or Brønsted acid-catalyzed rearrangements is described. Exhaustive NMR characterization of the obtained compounds is presented. Additionally the structures of some of the obtained compounds were confirmed by single crystal X-Ray Diffraction studies.
Subject(s)
Benzylidene Compounds/chemistry , Spirostans/chemistry , Catalysis , Hydrogenation , Models, Molecular , Molecular ConformationABSTRACT
BF3·Et2O-catalyzed double aldol condensation between acetylated steroid sapogenins and terephtalaldehyde led to acetylated dimeric spirostanols linked through a 1,4-dimethylidenebenzene moiety in moderate to good yields. The E configurations of the introduced double bonds were corroborated by NOE experiments. Saponification of the dimeric steroids led to the corresponding dimeric spirostanols.
Subject(s)
Aldehydes/chemistry , Benzene/chemistry , Boranes/chemistry , Dimerization , Ether/chemistry , Phthalic Acids/chemistry , Sapogenins/chemistry , Spirostans/chemical synthesis , Catalysis , Chemistry Techniques, Synthetic , Spirostans/chemistry , StereoisomerismABSTRACT
BF3·Et2O-catalyzed aldol condensation of steroid sapogenins with 2-formyl-estradiol diacetate afforded two novel classes of steroid dimers in which an estrogenic core is attached to the spirostanic side chain of an steroid sapogenin through an exocyclic double bond in position C-23, or through a spiro centre in C-22.
Subject(s)
Aldehydes/chemistry , Estradiol/chemical synthesis , Sapogenins/chemistry , Steroids/chemistry , Aldehydes/chemical synthesis , Benzaldehydes/chemical synthesis , Benzaldehydes/chemistry , Catalysis , Estradiol/analogs & derivatives , Estradiol/chemistry , Magnetic Resonance Spectroscopy , Sapogenins/chemical synthesis , Stereoisomerism , Steroids/chemical synthesisABSTRACT
Benzylidenespirostanols were prepared by two-step synthesis including BF3·Et2O-catalyzed aldol condensation of several acetylated steroid sapogenins with benzaldehyde followed by saponification. The obtained compounds showed moderate cytotoxicity against three cancer cell lines (T-lymphoblastic leukemia cell line CEM, breast carcinoma cell line MCF7 and cervical carcinoma cell line HeLa) and normal human fibroblasts (BJ). The most active of the five tested substances was 3c (lowest IC50 for MCF7 cells 19.9±0.1µM) without any selectivity towards human cancer and normal cells, respectively.
Subject(s)
Antineoplastic Agents, Phytogenic/chemical synthesis , Sapogenins/chemical synthesis , Spirostans/chemical synthesis , Steroids/chemical synthesis , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Cell Line, Tumor , Cell Proliferation/drug effects , Drug Screening Assays, Antitumor , Humans , MCF-7 Cells , Sapogenins/chemistry , Sapogenins/pharmacology , Spirostans/chemistry , Spirostans/pharmacology , Steroids/chemistry , Steroids/pharmacologyABSTRACT
Tandem aldol condensation between steroid sapogenins and hydroxylated benzaldehydes afforded steroidal spirochromenes. Compounds that bear a phenolic hydroxyl group at position C-6', obtained by a reaction with 2,5-dihydroxybenzaldehyde, showed approximately 80% of maximal radical scavenging activity in the 1,1-diphenyl-2-picrylhydrazyl radical (DPPH) assay at 288 nM. In contrast, the starting steroid sapogenins and the spirochromenes without a phenolic group in the side chain proved to be inactive.
