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(−)-(1R,2S,5R)-Menthyl (SS)-p-toluenesulfinate and its enantiomer are a common source for a chiral sulfoxide group in organic synthesis, by means of nucleophilic substitution. The replacement of the menthyloxy group, with complete inversion of configuration at the sulfur center of the chiral sulfoxide, allows the inclusion of this organic function into numerous substrates, with defined stereochemistry and high enantiomeric purity. Nine C3-substituted, enantiomerically pure, 2-sulfinylfurans were prepared by this synthetic methodology with moderate to high yields. These enantiopure C3-substituted 2-sulfinylfurans can be used as chiral dienes for [4+3] cycloaddition reactions and in other chemical transformations, in which π-facial selectivity should be induced in order to obtain enantioselective reactions.

The use of the p-tolylsulfinyl group as a chiral inductor in stereoselective [4+3] cycloaddition reactions has made possible the preparation of enantiopure polysubstituted 8-oxabicyclo[3.2.1]oct-6-en-3-one systems having up to five stereocenters. The presence in the furan diene of a susbtituent at the 3-position bearing an atom with lone-pair electrons propitiates the coordination of a metallic atom by the sulfoxide and the R3 “ligand” group. This chelation effect, together with the stereoelectronic demand of the R3 and sulfoxide groups, considerably decreases the degree of conformational freedom of the diene moiety in the cyclic transition state leading to the observed stereoselectivity. By choosing appropriate substituents in the furan ring, it is possible to obtain 100:0 cis-trans and 100:0 endo-exo diastereoselectivities. Up to 100 % π-facial diastereoselectivity (enantioselectivity after removal of the sulfoxide group) could be reached. Yields lie within the range of 50–80 %, depending on the furan substrate. However, if the furan diene is fitted with deactivating electron-withdrawing substituents, low conversions were observed under certain reaction conditions, but always with excellent-to-complete chemo- and stereoselectivities. The conversion and yield increase on introduction of an electron-donating substituent at the C-3 of the furan ring.

Several C-3 substituted furans with chelating groups have been reacted with 2,3-dibromo-3-pentanone in the presence of a reducing metal, resulting in the formation of [4+3]-cycloadducts with complete cis–trans and endo–exo diastereoselectivity and in excellent yield. A certain variability of the conversion and reaction yield could be observed, when changing the reaction conditions, but in all cases the stereoselectivity was complete, compared to that of C-3 substituted furans with non-chelating groups. Also, a general method of assignment of stereochemistry of cycloadducts has been established by NMR, considering diagnostic patterns of signals with different multiplicity and chemical shifts depending on the stereochemistry of diastereomeric cycloadducts.

An α-benzyloxyketone forming part of a strained cyclopentane carbon framework when treated with 10 equiv of anhydrous NaOH in absolute ethanol, for 2 h, affords in a 65% yield a new 2-benzyl-2-hydroxyketone, resulting from an unprecedented double benzylic rearrangement. This new rearrangement could be interpreted as an initial benzylic 1,4-shift between the O-enolate alkoxide of the ketone group and the oxygen atom of the benzyloxy ether, followed by a Curtin type benzylic 1,2-shift. Apart from the novelty and the synthetic application of this transformation it is worth noting the complete regio- and stereoselectivity observed. The structures of both substrate and product have been confirmed by X-ray diffraction studies. A tentative mechanism is herein proposed.

The ideal drug discovery process of new platinum based drugs should take into account three basic fundaments: on one side the mechanisms of action and the corresponding target biomolecules, on the other side, the possible mechanisms of resistance of cancer cells and their biochemical pathways and, finally, the pharmacokinetic and toxicity properties (ADMET) that will condition the clinical usefulness of the new drugs. At the end of this rational process always we face the necessity to design a molecule with a structure and certain physical and chemical properties. The structure is then a key fundamental issue when thinking of new anticancer platinum compounds. When analyzing the influence of molecular structure on anticancer activity it is useful to make the dissection of platinum complexes into different significant subunits or moieties, of the molecular structure. Thus, the following structural and electron dependent parameters are important to facilitate the comparison among platinum complexes: a) Nature of the non-labile ligand or carrier ligand (NLG); b) Nature of the labile ligand or leaving group (LG); c) Oxidation state of platinum atom; d) Type of atoms (connecting atoms X, Y, Z, W) that link ligands to platinum atom; e) Nature of the axial groups (AG) in platinum(IV) complexes; f) Nuclearity or number of Pt atoms in the platinum complexes; g) Formal charges present in the molecule and h) Intrinsic bioactivity of some ligands or bioactivity induced by molecules attached to ligands by linkers (in order to get a double mechanism of action or a parallel biological activity).

The platinum(II) complex cis -[(1 S ,2 R ,3 S )-1,7,7-trimethylbicyclo[2.2.1]heptane-2,3-diamine]dichloroplatinum(II) ( 1 ) and its enantiomer ( 2 ) have been synthesized and physically and spectroscopically characterized. To obtain the enantiopure complexes the chiral pool approach was applied. The synthetic pathway has four steps, starting from (±)-diphenylethylenediamine (DPEDA) ( 3 ) and the natural products (1 S )-camphorquinone or (1 R )-camphorquinone to obtain enantiomers 1 and 2 , respectively. The interaction of the Pt(II) complexes with DNA was studied by several techniques: circular dichroism, electrophoresis on agarose gel and atomic force microscopy (AFM). These studies showed differences in the degree of interaction between both enantiomers and DNA (calf thymus DNA and plasmid pBR322 DNA). The cytotoxicity of enantiomers 1 and 2 against the HL-60 cell line was studied by in vitro tests of antiproliferative activity, incubating during both 24 h and 72 h. An important difference of activity was found between both enantiomers regarding the IC 50 data at 24 h of incubation. Thus, complex 1 showed to be much more active than its enantiomer 2 .

A variety of C-3 functionalized chiral sulfoxide-containing furan derivatives is prepared, mainly based on manipulation of the carboxyl-moiety in (III).

Diastereoisomeric epimers at C1′ of 4-(1-methyl-2-oxo-butyl)-2-butenolide, and the corresponding saturated γ-lactones, were synthesized by hydrolysis of 1-methoxy-8-oxabicyclo[3.2.1] oct-6-en-3-one, under acidic conditions. These butenolides are interesting synthetic building blocks, precursors of biologically active natural products like insect pheromones. Their formation could be explained by a cleavage at the C1–C2 bond of the oxabicyclic precursor. On the basis of the experimental data we have proposed a mechanism of hydrolytic cleavage which is formally an intramolecular reverse Dieckmann process.