Juan Alberto Marco

Synthesis of conjugated δ-lactams using ring-closing metathesis

Abstract Addition of allyl magnesium or metallyl magnesium bromide to the N -benzyl imines of benzaldehyde and cyclohexanone, followed by acylation with acryloyl or metacryloyl chloride provided the corresponding α,β-unsaturated amides. Ring-closing metathesis of the latter with ruthenium catalyst PhCHRuCl 2 (PPh 3 ) 2 in the presence of Ti(O i Pr) 4 provided excellent yields of the corresponding conjugated δ-lactams with both disubstituted and trisubstituted CC bonds. Some specific trisubstitution patterns, however, as well as tetrasubstituted CC bonds, were not obtained. In these cases, even the use of a second generation, imidazolylidene-substituted ruthenium catalyst at high temperature did not lead to success.

Aldol Reactions with Erythrulose Derivatives: Stereoselective Synthesis of Differentially Protected syn-α,β-Dihydroxy Esters

Boron enolates of 1-O-silylated erythrulose 3,4-acetonides prepared with Browns chloro-dicyclohexylborane/tertiary amine system have been shown to react with achiral aldehydes in a highly stereoselective way to yield a 1,2-syn/1,3-syn stereoisomer. Through oxidative cleavage of the aldol adducts with periodic acid hydrate, enantiopure syn-α,β-dihydroxy esters with either hydroxyl group differently protected have been prepared. These erythrulose derivatives therefore behave as a chiral hydroxy acetate (glycolate) enolate equivalent.

Influence of the protecting groups on the syn/anti stereoselectivity of boron aldol additions with erythrulose derivatives. A theoretical and experimental study

Abstract We have investigated a series of aldol additions of protected l -erythrulose derivatives mediated by dicyclohexyl boron chloride. The syn / anti stereoselectivity has been found to depend on the type of protecting groups on the hydroxyl functions at C-3 and C-4. Thus, erythruloses benzylated at these hydroxyl groups gave only syn aldols while the corresponding benzoylated derivatives gave anti aldols under the same reaction conditions. The resident chirality of the enolate promoted a complete internal 1,3-induction, which was syn in both aldol types. Mechanistic proposals are advanced with support of both theoretical calculations and experimental data.

An ab initio study of the enolboration of 3-pentanone mediated by boron monochlorides L2BCl

Abstract Using ab initio methods at the HF/6-31G∗∗ level, we have studied the mechanism of the enolboration of 3-pentanone mediated by boron monochlorides L2BCl (L=H, methyl and isopropyl) and trimethyl amine. The size of the L group has been found to have a decisive influence on the configuration (E or Z) of the formed boron enolate. Thus, whereas our calculations predict that dimethylboron chloride yields the Z enolate with high stereoselectivity, diisopropylboron chloride is found to yield predominantly the E enolate. The difference in behavior is due mainly to steric features related to the conformational bias of the respective ketone–boron chloride complexes formed reversibly in the first step of the process. These findings, which are in good agreement with experimental results in aldol reactions with L2BCl reagents, provide a compelling theoretical explanation for the stereochemical outcome of such reactions.

The Mechanism of the Interactions of Pironetin Analog/Combretastatin A-4 Hybrids with Tubulin

We here report an investigation of the interactions with tubulin of two types of molecules of a hybrid structural type consisting in a combretastatin A‐4 moiety and a simplified pironetin fragment. The cytotoxicities of the molecules on two reference tumoral cell lines were measured. In addition, the effects of the compounds on the cell cycle and on microtubule assembly were observed. The dynamics of microtubule polymerization was investigated by means of immunofluorescence assays. It was thus established that at least some of the compounds under study exert their cytotoxic action by means of interaction with tubulin.

Synthesis of Honokiol Analogues and Evaluation of their Modulating Action on VEGF Protein Secretion and Telomerase‐Related Gene Expressions

A group of 36 biphenyl derivatives structurally related to honokiol were synthesized by means of Suzuki coupling reactions. Their cytotoxicities were evaluated and compared to that of honokiol. Some of the compounds were then evaluated for their ability to downregulate the secretion of the VEGF protein and the expression of the VEGF, hTERT, and c‐Myc genes; the two latter involved in the activation of telomerase in tumoral cells. Some of the synthetized derivatives showed promising pharmacological features as they exhibited IC50 values in low micromolar range, good therapeutic margins, and a multiple mode of action on tumor cells based on the inhibition of VEGF and, at the same time, of the expression of genes related to the activation of telomerase.

2.14 Selected Diastereoselective Reactions: Enolate Alkylation

This chapter discusses processes in which enolates are subjected to reaction with alkylating reagents. In all the processes examined here, at least one of the two reaction components is chiral and the reaction gives rise to one or more diastereomeric compounds. In most cases, the enolate is generated through deprotonation of the corresponding carbonyl precursor with a suitable base, but in several cases, the enolate is generated differently, for example, through Michael addition of a nucleophile to a conjugated carbonyl compound. The various factors that have been found to influence the stereochemical outcome of the alkylation reaction in a measurable way are also discussed. The material has been organized according to the type of carbonyl precursor used and then categorized with regard to its cyclic or acyclic nature. The pertinent information has been taken from studies published between 1995 and 2010.