ABSTRACT
Platinum (II) complexes are accredited with biological activities. New complexes with thiepane dioxide diamine as ligands, characterized by defined stereochemical features, a flexible 7-membered thiepane moiety and by C2 symmetry, were prepared. The complexes, related to the diamino cyclohexane family of platinum complexes, were soluble in dimethyl sulfoxide with the solvent substituting one chloride ion. These positively-charged complexes were tested against a human carcinoma cell line A431 and its cisplatin-resistant counterpart A431/Pt and were found to show: i) capability in bypassing cisplatin-resistance; ii) cytotoxicity comparable to that of oxaliplatin; iii) lower activity than cisplatin. In both cells lines, [PtCl(DACH)(DMSO)]+ was more cytotoxic than oxaliplatin. The best activity was shown by the platinum complexes with ligands which presented C2 symmetry.
Subject(s)
Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Organoplatinum Compounds/chemistry , Organoplatinum Compounds/pharmacology , Antineoplastic Agents/chemical synthesis , Cell Line, Tumor , Cisplatin/pharmacology , Drug Resistance, Neoplasm , Drug Screening Assays, Antitumor , Female , Humans , Ligands , Organoplatinum Compounds/chemical synthesis , Oxaliplatin , Oxides/chemical synthesis , Oxides/chemistry , Oxides/pharmacology , Stereoisomerism , Thiepins/chemical synthesis , Thiepins/chemistry , Thiepins/pharmacology , Uterine Cervical Neoplasms/drug therapyABSTRACT
A straightforward synthetic protocol apt to synthesize a library constituted by all conduritol stereoisomers in solution phase is described and successfully applied to some polymer-supported substrates. During the solid-phase sequence, an unprecedented rearrangement of a resin-bound sulfone performed under the Ramberg-Bäcklund conditions appears of particular interest. Upon treatment with Me(3)Si-I, thiepanes supported on resin are found to undergo regio- and stereospecific ring contraction to a six-membered ring system with traceless cleavage from the solid support.
Subject(s)
Combinatorial Chemistry Techniques/methods , Cyclohexanols/chemical synthesis , Thiepins/chemistry , Cyclohexanols/chemistry , Magnetic Resonance Spectroscopy , Molecular Structure , StereoisomerismABSTRACT
Optically pure enantiomers of the chiral tetrahydroxythiepane derivative 3,6-dihydroxy-4,5-O-isopropylidene-thiepane (3) are obtained using a novel protocol in which a library of all possible stereoisomers of 3 is synthesized, followed by two-step stereoselective chromatography, using, first, conventional achiral and, then, chiral stationary phases. Configurational and conformational analysis of 3 are carried out using Vibrational Circular Dichroism (VCD) spectroscopy in conjunction with ab initio DFT calculations. The absolute configuration of 3 is shown to be 3R,4S,5R,6R-(+)/3S,4R,5S,6S-(-).
ABSTRACT
The enantioselective synthesis of bicyclic sulfonium salts 8 or 9, thioanalogues of swainsonine derivatives, is described. The synthetic strategy is based on a stereo- and regiospecific transannular cyclization reaction of nine-membered cyclic sulfides, mediated by Me(3)SiI or carried out under acidic catalysis.
Subject(s)
Combinatorial Chemistry Techniques , Sulfonium Compounds/chemistry , Swainsonine/chemical synthesis , Catalysis , Cyclization , Glucosamine/analogs & derivatives , Glucosamine/chemical synthesis , Hydrogen-Ion Concentration , Indicators and Reagents , Indolizines/chemical synthesis , Indolizines/chemistry , Molecular Structure , Stereoisomerism , Swainsonine/chemistryABSTRACT
Oxime ethers derived from 2-pyridinecarboxaldehyde and glyoxylic acid can be effectively allylated in water with five differently functionalized allylic bromides promoted by indium. When the metal is positioned in close proximity of flanking heteroatomic centers, chelation by In is indeed operative and affects both reactivity and stereochemistry. Stereochemical assignments in the addition products were based on X-ray crystallographic measurements and spectral correlations.
