Mercedes Amat

Chiral precursors for the synthesis of enantiomerically pure piperidines. Total synthesis of (R)-(-)-coniine

Abstract The preparation of chiral cis - and trans -oxazolopiperidones 1 , 2 , and 3 by alternative procedures and an efficient synthesis of the piperidine alkaloid ( R )-(-)-coniine from trans - 1 is reported.

Palladium-catalyzed heteroarylation of 1-(tert-butyldimethylsilyl)-3-indolylzinc chloride. Efficient synthesis of 3-(2-pyridyl)indoles

Abstract Palladium-catalyzed coupling of 1-( tert -butyldimethylsilyl)-3-indolylzinc chloride ( 2 ) with either π-deficient or π-excedent heteroaryl halides gives 3-arylindoles in good to excellent yields. The method is extensively applied to the preparation of 3-(2-pyridyl)indoles.

An efficient synthesis of 2-(2-pyridyl)indoles by palladium(0)-catalyzed heteroarylation

Abstract A general method for the preparation of 2-(2-pyridyl)indoles based on the palladium(0)-catalyzed coupling of 1-(benzenesulfonyl)-2-indolylzinc chloride with 2-halopyridines is reported.

Enantioselective Formal Synthesis of (+)-Dihydrocorynantheine and (-)-Dihydrocorynantheol †

The enantioselective construction of the 3-ethylindolo[2,3-a]quinolizidine moiety present in numerous indole alkaloids is reported, the key steps being a stereoselective cyclocondensation of (S)-tryptophanol with an appropriate racemic delta-oxoester and a regio- and stereoselective cyclization of the resulting oxazolopiperidones on the lactam carbonyl group. A new procedure for the removal of the hydroxymethyl auxiliary group, involving oxidation to an aldehyde, dehydration of the corresponding oxime, and reductive decyanation of the resulting alpha-aminonitrile, has been developed. The preparation of indoloquinolizidine 27 represents a formal total synthesis of (+)-dihydrocorynantheine, (-)-dihydrocorynantheol, and other indolo[2,3-a]quinolizidine and oxindole alkaloids bearing the same substitution pattern.

TOTAL SYNTHESES OF THE STRYCHNOS INDOLE ALKALOIDS (-)-TUBIFOLINE, (-)-TUBIFOLIDINE, AND(-)-19,20-DIHYDROAKUAMMICINE

Abstract Two different stragies for the synthesis of pentacyclic Strychnos alkaloids in enantiomerically pure form are explored. Both of them involve the use of enantiopure 2-(4-piperidylmethyl)indoles prepared by kinetic resolution of 1-(3-pyridyl)ethanol, followed by partial reduction of the pyridine ring to the tetrahydropyridine level, Claisen rearrangement of the resulting allylic alcohol, and finally Smith indolization. Whereas 2-(4-piperidylmethyl)indole 6 could not be converted to tetracyclic ABDE substructures of Strychnos alkaloids, photocyclization of chloroacetamide 14 , derived from (piperidylmethyl)indole 13 , satisfactorily afforded the stemmadenine-type tetracycle 15 , which was then converted to the alkaloids (−)-tubifoline, (−)-tubifolidine, and (−)-19,20-dihydroakuammicine.

Preparation of enantiopure 6-(3-indolyl)-2-piperidones and conjugate additions to a 3,4-didehydro derivative

Amidoalkylation of chiral non-racemic lactams 1–3 with indole in the presence of TiCl4 provides enantiopure 6-(3-indolyl)-2-piperidones 4a,b–6a,b. The stereochemical course of the conjugate addition of a variety of functionalized carbon nucleophiles to 5,6-dihydro-2-pyridone 11, derived from 4a, is studied.

Stereoselective Conjugate Addition Reactions to Phenylglycinol‐Derived, Unsaturated Oxazolopiperidone Lactams

Phenylglycinol-derived, unsaturated oxazolopiperidone lactams are extremely useful building blocks that undergo stereoselective conjugate addition reactions with organocuprates, enolates, and sulfur-stabilized anions, allowing the stereocontrolled introduction of substituents at the piperidine 4-position. The factors governing the exo- or endo-facial selectivity are discussed. The methodology can be used for the preparation of a variety of enantiopure piperidines, including pharmaceuticals, alkaloids precursors, piperidine-fused derivatives, as well as complex piperidine-containing natural products.

'Click' synthesis of a triazole-based inhibitor of Met functions in cancer cells.

The use of Cu(I)-catalyzed azide-alkyne 1,3-dipolar cycloaddition permitted the synthesis of a new compound that is able to inhibit the HGF-induced scattering of MDCK (epithelial cells) and in vitro tumorigenesis of H1437 (non-small-cell lung cancer) and GTL-16 (human gastric carcinoma). In agreement with biochemical and biological results, docking studies within the ATP binding site of Met suggested for the new synthesized compound a binding mode similar to that of the active compound Triflorcas previously reported.

Synthesis of enantiopure piperidines. Total synthesis of (2R,6S)-2-methyl-6-propylpiperidine [(−)-dihydropinidine]

Abstract Enantiomerically pure 2-alkyl-, 3-alkyl-, 4-alkyl-, and cis -2,6-dialkylpiperidines are prepared from the chiral, non-racemic oxazolopiperidone 1 . An asymmetric synthesis of (2 R ,6 S )-(−)-dihydropinidine is reported.

Enantioselective formal synthesis of ent-rhynchophylline and ent-isorhynchophylline

Starting from (S)-tryptophanol, a formal synthesis of ent-rhynchophylline and ent-isorhynchophylline, involving stereoselective cyclocondensation, spirocyclization, and alkylation reactions, and the final adjustment of the oxidation level at the oxindole and piperidine moieties, is reported.