Asensio González

Isatin derivatives, a novel class of transthyretin fibrillogenesis inhibitors

The isatin core structure was found to be a novel chemical scaffold in transthyretin (TTR) fibrillogenesis inhibitor design. Among the series of isatin analogues prepared and tested, the nitro compound 1,3-dihydro-3-[(4-nitrophenyl)imino]-2H-indol-2-one (2r) is as potent as triiodophenol, which is one of the most active known TTR inhibitors. The E/Z stereochemistry of these molecules in solution, elucidated by (1)H NMR, does not influence their biological activity. The compounds do not bind to the native tetrameric TTR suggesting that their inhibitory action is independent of the protein binding and stabilization.

Photochemical desulfurization of l-cysteine derivatives

Abstract Thiol groups can be reductively eliminated at room temperature by a photochemical method which makes use of triethylboron, triethylphosphite and visible light. Thus, after treating l -Cys 1a , d -Pen 1b , l -Cys-OMe 1c and glutathione (γ- l -Glu- l -Cys-Gly) 3 , the corresponding desulfurized compounds l -Ala 2a , d -Val 2b , l -Ala-OMe 2c and γ- l -Glu- l -Ala-Gly 4 , respectively, are prepared in high yields and with retention of configuration.

PHOTOCHEMICAL DESULFURIZATION OF THIOLS AND DISULFIDES

Abstract A visible light-induced desulfurization process for thiols and disulfides using triethylphosphite and triethylborane is reported. The reaction can be effected on a range of organic molecules having either primary, secondary or tertiary thiol groups and disulfides without the need of protecting groups. Thus, after treating l -cystine 7 , l -cystine dimethylester 8 , thioctic amide 9 and glutathione disulfide 10 , first with tributylphosphine, later with triethylborane/triethylphosphite under irradiation in a one-pot reaction, the corresponding desulfurized compounds l -Ala, l -Ala, 1-octanamide and γ- l -Glu- l -Ala-Gly, respectively, are prepared in high yields with retention of configuration.

PROTECTED DERIVATIVES OF (R)-CYSTEINE AND (R)-CYSTEINOL

Abstract The synthesis of N, O, S protected forms of ( R )-cysteine and ( R )-cysteinol as bicyclic derivatives is described. The reactivity and the preparation of substituted derivatives of these systems is also discussed.

Boron complexes of S-trityl-l-cysteine and S-tritylglutathione

Abstract S -Trityl- l -cysteine and S -tritylglutathione have been converted to 1,3,2-oxazaborolidine-5-ones by reaction with B -methoxydialkylborane derivatives. The synthesis of dicyclohexyl[ S -trityl-( R )-cysteinato- O , N ]boron ( 2 ), diisopinocampheyl[ S -trityl-( R )-cysteinato- O , N ]boron ( 3 ) and 9-borabicyclo[3.3.1]non-9-yl[ S -tritylglutathionato- O , N ]boron ( 5 ), dicyclohexyl[ S -tritylglutathionato- O , N ]boron ( 6 ) and diisopinocampheyl[ S -tritylglutathionato- O , N ]boron ( 7 ) from S -trityl- l -cysteine and S -tritylglutathione, respectively, with potential application in boron neutron capture therapy is reported. The structure of 9-borabicyclo[3.3.1]non-9-yl[ S -trityl-( R )-cysteinato- O , N ]boron 1 has been determined by X-ray diffraction.

Cyclopalladated primary amines: a preliminary study of antiproliferative activity through apoptosis induction.

Twelve cyclometallated palladium(II) complexes containing primary aromatic amines [benzylamine (a), (R)-1-(1-naphthyl)ethylamine (b) and 2-phenylaniline (c)] as anionic bidentate (C,N)(-) ligands have been evaluated against a panel of human adenocarcinoma cell lines (A549 lung, MDA-MB231 and MCF7 breast, and the cisplatin resistant HCT116 colon). The results revealed a remarkable antiproliferative activity of the triphenylphosphane mononuclear compounds 3-4 (series a, b, c) and the best inhibition was provided for 3c and 4c with the 2-phenylaniline ligand and a six membered chelate ring. Interestingly, 3c and 4c were 14 and 19 times more potent than cisplatin for the inhibition of the cisplatin resistant HCT116 human adenocarcinoma cell line, respectively. Cyclopalladated complexes 3c and 4c exercise their antiproliferative activity over A549 cells mainly through the induction of apoptosis (38 and 31-fold increase in early apoptotic cells, respectively).

Synthesis and Evaluation of Novel Boron-Containing Complexes of Potential Use for the Selective Treatment of Malignant Melanoma

Boron-containing complexes that have the potential to irreversibly accumulate in melanoma cells have been prepared by reaction of amino acids with 9-methoxy-9-borabicyclo[3.3.1]nonane. The ability of each complex to act as a substrate for tyrosinase has been probed by oximetry. Increased uptake of the lead candidate in a tyrosinase-rich cell line, compared with a tyrosinase-absent cell line, is reported, with results correlating well with that for a drug currently approved for BNCT.

Visible light promoted organic reaction on a solid support

Abstract The first example of a photochemical reaction promoted by visible light irradiation on a solid support is described.

Asymmetric Synthesis of 2-Arylpropionic Acids

Abstract The preparation of (S)-2-(6-methoxy-2-naphtyl)propionic acid (S-Naproxen) 1 and (S)-2-(4-isobutylphenyl)propionic acid (S-Ibuprofen) 2, based on asymmetric alkylation of oxazolidiones 9 and 14, is reported.

Chiral dienolates : Stereoselective formation and α-alkylation of the lithium dienolates derived from (RS)-Z-[(n5-C5H5)Fe(CO)(PPh3)COCHCHCH2R] (RMe,Et,n-pr) and (RS)-[(n5-C5H5)Fe(CO)(PPh3)(COCHCMme2)]

Abstract The acyl ligands Z-(COCHCHCH2-R)(RMe,Et, n -Pr) and (COCH-CMe2) bound to the chiral auxiliary [(n5 -C5H5)Fe(CO)(PPh3)] undergo exclusive γ-deprotonation to form the corresponding dienolates which react with electrophiles regio- and stereoselectively at the α-position to give in most cases single diastereoisomers of the corresponding α-substituted-βγ-unsaturated acyl complexes, together with in the former cases complete control over the β,γ-double bond geometry (E).