Angèle Chiaroni

Diphenyl quinolines and isoquinolines: synthesis and primary biological evaluation.

The synthesis of a series of 35 substituted 3,4-diphenyl quinolines and isoquinolines is described. The majority of these molecules differ from all other triphenylethylene based antiestrogens by a different spatial location of the aminoalkyl side chain. The binding affinity of the most representative molecules (8, 9, 19, 20, 21, 23 and 25), including analogues 8 and 21 without the side chain, for the estrogen receptor alpha (ER) was determined. The ability of these molecules to induce the progesterone receptor was also studied. Antiproliferative activity was evaluated on MCF-7 human breast cancer cells, while intrinsic cytotoxic/cytostatic properties resulting from interaction with other targets than ER were assayed on L1210 murine leukemia cells. Introduction of an aminoalkylamino side chain at carbon 2 confers strong cytotoxic properties to diphenylquinolines 9 and 10 as well as pure antiestrogenic activities. However, cytotoxicity is so high with respect to antiestrogenicity that the latter was clearly observable only in one case (9b). The structure of compound 9b was determined by X-ray crystallography. Molecular modeling of its docking within the hormone-binding domain of the receptor was subsequently undertaken. According to our results, the design of molecules with the side chain bound to the ethylene part of the triphenyl ethylene skeleton might generate compounds of potential pharmacological interest.

One-Pot Three-Component Synthesis of alpha -Iminonitriles by IBX/TBAB-Mediated Oxidative Strecker Reaction

The reaction of aldehydes, amines, and TMSCN in the presence of 2-iodoxybenzoic acid (IBX) and tetrabutylammonium bromide (TBAB) afforded alpha-iminonitriles in good to excellent yields under mild conditions. The presence of TBAB is essential for this transformation. The methodology was applied to a two-step synthesis of indolizidine via a microwave-assisted intramolecular cycloaddition of alpha-iminonitrile.

New nitrogenous and aromatic derivatives from Aglaia argentea and A. forbesii

Seeds and leaves of Aglaia argentea and bark of A. forbesii were extracted. The known cyclopentatetrahydrobenzofuran derivative rocaglaol (1) and the aminopyrrolidine odorine (5), were isolated together with nine new compounds: didesmethylrocaglamide (6), aglains A (7), B (8) and C (9), aglaforbesins A (10) and B (11), ethylrocaglaol (12) and forbaglins A (13) and B (14). Compounds 7–11 and 13,14 possess a new cyclopentatetrahydrobenzopyran and benzoxepine skeleton, respectively, linked to an odorine type moiety. All the structures were elucidated notably by 2D NMR spectroscopy. In addition, the structure of forbaglin A was established by X-Ray crystallographic analysis. Didesmethylrocaglamide revealed strong cytotoxic activity against KB cells (IC50 0.006 μg/ml).

Oxydation et addition des dihalocarbènes sur le β-himachalène

Resume Reaction of β-himachalene with one equivalent of dihalocarbene, KMnO 4 or m -CPBA gives regio- and stereospecifically one product resulting from the attack of the C6 C7 double bond. The molecular structure shows that this attack occurs on the α face of this double bond.

Enantioselective synthesis of cyclopropane α-amino acids: Synthesis of N-Boc-cis-(2S,3R,4S)-3,4-methanoproline and N-Boc-(2S,3R,4S)-3,4-methanoglutamic acid

Abstract The title compounds were synthesized by a 5-step facile transformation of the key intermediate 4, itself obtained by a “one-pot” sulfone-mediated cyclopropanation from chiral synthon (R)-1 and (2 R )-glycidyl triflate.

The asymmetric michael addition process involving chiral imines : stereochemical data in support of a cyclic-like transition state

Abstract Additions of imine 4 to Michael acceptors 5 and 8 are both highly selective processes. The observed stereocontrol of the newly created asymmetric centers in the resulting adducts strongly supports cyclic-like transition states.

Asymmetric synthesis. XXXI: Synthesis of 2-substituted piperazines from chiral non-racemic lactams

Abstract A series of 3-substituted piperidines in enantiomerically pure form has been synthetized from lactam 3 by a stereospecific route involving a postulated rigid amide enolate. This strategy has been applied to the synthesis of (+)-stenusine 10.

1,3-Dipolar cycloadditions of nitrones to α,β-unsaturated γ-lactams derived from (S)-pyroglutaminol☆

Abstract α,β-Unsaturated γ-lactams undergo regio- and stereoselective 1,3-dipolar cycloadditions with N-benzyl and N-methyl nitrones and can act as acceptors in conjugate addition of N-methylhydroxylamine. These reactions give access to highly functionalized pyrrolidones.

Composés bromés de Rytiphlea tinctoria (Rhodophyceae)

Abstract Four aromatic bromo compounds have been isolated from the ethanolic extract of Rytiphlea tinctoria after treatment with diazomethane: 2,4-dibromo-1,3,5-trimethoxy-benzene,5,6,3′,5′-tetrabromo-3,4,2′,4′,6′-pentamethoxydiphenylmethane, 5,6-dibromo-3,4-dimethoxy-benzyl alcohol and its ethyl ether. In addition to sterols, amino acids, this extract also contains quinonoid bromo-pigments which could play a role in photosensitisation of chlorophylls, a role normally taken by the phycobilins, in other Rhodophyceae.

An efficient method for the stereoselective synthesis of cis-3-substituted prolines: conformationally constrained α-amino acids

Abstract An efficient synthesis of enantiomerically pure cis-3-substituted prolines is reported. Key steps involve the stereoselective organocuprate addition to the (E)-α,β-unsaturated ester 1 , obtained from the Garners aldehyde, and expedient oxidation–cyclization sequences.