Giordano Lesma

Grignard addition to imines derived from isatine: a method for the asymmetric synthesis of quaternary 3-aminooxindoles.

Addition of Grignard reagents to chiral imines derived from isatine afforded chiral, optically enriched 3-substituted 3-aminooxindoles in satisfactory yields and diastereoisomeric ratios. A general protocol is described for the addition of alkyl, alkenyl, and aryl Grignard reagents. In one case, the absolute configuration at C3 was determined and the selective N-deprotection was described, enabling further synthetic transformations of the reaction product.

Olefin Metathesis Based Approach to Diversely Functionalized Pyrrolizidines and Indolizidines; Total Synthesis of (+)-Monomorine

New scaffolds for the stereoselective synthesis of diversely functionalized chiral enantiopure indolizidines and pyrrolizidines were synthesized from the cross and ring-closing metathesis reactions of appropriate intermediates, readily available from L-pyroglutamic acid. The versatility of this strategy was demonstrated by the synthesis of an indolizidine-based azasugar analogue and of the natural alkaloid (+)-monomorine.

Synthesis of enantiopure diamine ligands related to sparteine, via scandium triflate-catalyzed imino Diels–Alder reactions

Imino Diels–Alder reactions have been investigated as a new route to sparteine analogues. The first enantioselective synthesis of two diastereoisomeric tricyclic diamines, structurally equivalent to the ABC and BCD rings of the naturally occurring alkaloid, is reported, starting from enantiopure intermediates. The effectiveness of the diamines in the lithiation of N-Boc-pyrrolidine is discussed.

Application of the Pd-catalyzed heteroarylation to the synthesis of 5-(indol-2′-yl)pyridin-2-one and 5-(indol-2′-yl)pyran-2-one

Abstract The synthesis of 5-(indol-2′-yl)pyridin-2-ones and 5-(indol-2′-yl)pyran-2-one by Pd-catalyzed reactions is described. The best results are obtained using 2-indolylstannanes or 2-indolylzinc halides to be coupled with 5-bromopyridin-2-ones or 5-bromopyran-2-one in the presence of Pd(PPh3)4 as catalyst. Other Pd-catalyzed reactions are discussed.

New solution free and polymer anchored chiral bispidine-based amino alcohols. Synthesis and screening for the enantioselective addition of diethylzinc to benzaldehyde

Abstract A new approach has been evaluated for the preparation of solution free and polymer supported chiral bicyclic amino alcohols. This strategy involves the use of readily available starting materials and allows chiral ligands characterised by the bispidine core, bearing a stereogenic centre β to one of the nitrogen atoms to be obtained. The first results obtained from the application of these ligands in the asymmetric addition reaction of diethylzinc to benzaldehyde are discussed.

Aspidosperma alkaloids via cyclization of secodine intermediate: Synthesis of (±)-3-oxovincadifformine ethyl ester.

Abstract (±)-3-oxovincadifformine ethyl ester 14 has been synthesized through an intramolecular [4π+2π] cycloaddition of the 3-oxosecodine 13 first prepared in turn from the enamide 10 by dehydrogenation with benzeneseleninic anhydride. An insight into the conversion of 10 into 13 was gained, resulting in the suggestion of a plausible mechanistic pathway.

Asymmetric Ugi 3CR on isatin-derived ketimine: synthesis of chiral 3,3-disubstituted 3-aminooxindole derivatives.

Summary An efficient Ugi three-component reaction of a preformed chiral ketimine derived from isatin with various isonitrile and acid components has been developed. The reactions proceeded smoothly and in a stereocontrolled manner with regard to the new center of the Ugi products due to the stereoinduction of the amine chiral residue. A wide variety of novel chiral 3,3-disubstituted 3-aminooxindoles were obtained, a selection of which were subjected to post-Ugi transformations, paving the way to application as peptidomimetics.

Ibogaine analogues. Synthesis and preliminary pharmacological evaluation of 7-heteroaryl-2-azabicyclo[2.2.2]oct-7-enes.

Synthesis of 7-heteroaryl-2-azabicyclo[2.2.2]oct-7-enes by cycloaddition and subsequent cross-coupling reaction is described. Binding affinity of these novel compounds towards the characteristic receptorial targets of ibogaine is illustrated.

Organocatalytic Asymmetric Biginelli-like Reaction Involving Isatin

The first asymmetric, Brønsted acid catalyzed Biginelli-like reaction of a ketone has been developed, employing N-substituted isatins as carbonyl substrates, and urea and alkyl acetoacetates as further components. BINOL-derived phosphoric acid catalysts have been used to achieve the synthesis of a small library of chiral, enantioenriched spiro(indoline-pyrimidine)-diones derivatives. The absolute configuration of the new spiro stereocenter was assessed on diastereoisomeric derivatives through computer-assisted NMR spectroscopy. X-ray diffractometry allowed the disclosure of the overall molecular conformation in the solid state and the characterization of the crystal packing of a Br-substituted Biginelli-like derivative, while computational studies on the reaction transition state allowed us to rationalize the stereochemical outcome.

Quinazolinecarboline alkaloid evodiamine as scaffold for targeting topoisomerase I and sirtuins

This paper reports the synthesis of a series of evodiamine derivatives. We assayed the ability to inhibit cell growth on three human tumour cell lines (H460, MCF-7 and HepG2) and we evaluated the capacity to interfere with the catalytic activity of topoisomerase I both by the relaxation assay and the occurrence of the cleavable complex. Moreover, whose effect on sirtuins 1, 2 and 3 was investigated. Finally, molecular docking analyses were performed in an attempt to rationalize the biological results.