Ramón J. Estévez

Synthesis of pyrrolizidines via copper(I) catalyzed radical atom transfer cyclization

Abstract Trachelanthamidine and pseudoheliotridane are synthesized from (2s)-N-trichloroacetyl-2-vinylpyrrolidine ( 5 ) by a 5-exo-trig- radical cyclization. The intermediate radical is generated heating 5 in a sealed tube (CH3CN/ 160°) using CuCl as catalyst and the cyclization occurs in very good yield (93%). Cyclized product 6 is transformed either into (−)-trachelanthamidine (55% yield from 5 ) or into (−)-pseudoheliotridane (42% yield from 5 ).

A short overview on the medicinal chemistry of (-)-shikimic acid.

Shikimic acid, a natural compound is a key intermediate in the biosynthesis of amino acids. Consequently, this derivative is widely present in many plants and has interesting biological properties. But besides the pharmacological relevance of shikimic acid itself, it is also an intermediate in the synthesis of many drugs, being the most relevant the antiviral agent oseltamivir (Tamiflu™). Here we present a short overview on recent natural, biotechnological and synthetical sources of shikimic acid, togheter with pharmacological applications of this compound and a selection of derivatives, including oseltamivir (Tamiflu™).

Tri- and tetra-peptides incorporating an α-amino acid at the anomeric position of mannofuranose

Abstract The first examples of peptides containing an α-amino acid residue in which the α-carbon is also the anomeric position of a carbohydrate are described.

Palladium-catalyzed synthesis of o-acetylbenzoic acids: a new, efficient general route to 2-hydroxy-3-phenyl-1,4-naphthoquinones and indolo[2,3-b]naphthalene-6,11-diones

Abstract We describe here a new, efficient general synthesis of o -acetylbenzoic acids by Heck palladium-catalyzed arylation of n -butyl vinyl ether with o -bromobenzoic acid esters and the use of these compounds as starting materials for the synthesis of 3-benzylideneisochroman-1,4-diones, which readily rearrange to 2-hydroxy-3-phenyl-1,4-naphthoquinones. The application of this strategy to the synthesis of indolo[2,3- b ]naphthalene-6,11-diones is also described.

A new, simple, efficient synthesis of benzo[b]carbazoles and indeno[1,2-b]indoles

Abstract A new, efficient synthesis of benzo[b]carbazoles and indeno[1,2-b]indoles from nitrophenylacetylphenylacetic acids and nitrobenzylphthalides respectively is described.

Heck-mediated synthesis and photochemically induced cyclization of [2-(2-styrylphenyl)ethyl]carbamic acid ethyl esters and 2-styryl-benzoic acid methyl esters: total synthesis of naphtho[2,1f]isoquinolines (2-azachrysenes) ☆

Abstract We describe two new closely related total syntheses of naphtho[2,1-f]isoquinolines. The first synthesis consists of a Heck coupling reaction between trifluoromethanesulfonic acid 2-(2-ethoxycarbonylaminoethyl)phenyl esters and styrenes to give [2-(2-styrylphenyl)ethyl]carbamic acid ethyl esters. These compounds cyclize to give (2-phenanthren-1-yl-ethyl)carbamic acid ethyl esters, from which 2-azachrysenes can be obtained in a three-step sequence. The second synthesis includes a new total synthesis of 2-styrylbenzoic acid methyl esters by Heck coupling of methyl o-iodobenzoates to styrenes, followed by the transformation of the resulting benzoic acid derivatives into phenanthrene-1-carboxylic acid methyl esters and then into the target compounds by a six-step sequence including a Bischler–Napieralski cyclization.

Synthesis of polyhydroxylated α-nitrocyclohexane carboxylic acids derived from D-glucose: a striking case of racemization

The first total synthesis of polyhydroxylated α-nitrocyclohexane carboxylic acids from sugars is reported. A salient aspect of the synthesis is an unexpected Henry-mediated racemization of this new class of highly functionalized cyclohexanes.

Radical cyclization to aporphines. A new, efficient total synthesis of the aporphine glaucine and the 4,5-dioxoaporphine pontevedrine, and the first total synthesis of 5-oxoaporphines.

Abstract We describe the radical cyclization of bromobenzylisoquinolines and benzylisoquinolin-3-ones, which afford aporphines or the novel 5-oxoaporphines and 5-oxodehydroaporphines respectively. Oxidation of the latter compounds provides a new route to 4,5-dioxoaporphines.

From Phenylacetylphenylacetic Acids and 1-Benzylisoquinolines to 6,11-Dihydrobenzo[b]naphtho[2,3-d]furan-6,11-diones, 6H-Dibenzo[c,h]chroman-6-ones and 7,12-Dihydro-5H-dibenzo[c,g]chroman-5,7,12-triones via 2-Phenyl-3-hydroxy-1,4-dihydro-1,4-naphthalenediones or 2-Phenyl-1-naphthols

Abstract We describe the synthesis of 6,11-dihydrobenzo[b]naphtho[2,3-d]furane-6,11-diones, 6H-Dibenzo[c,h]chroman-6-ones and 7,12-dihydro-5H-dibenzo[c,g]chroman-5,7,12-triones from 2-(2′-phenyl)-3-hydroxy-1,4-dihydro-1,4-naphthalenediones or 2-phenyl-1-naphthols obtained from 2-(2′-bromophenylacetyl)-phenylacetic acids or 1-benzylisoquinolines.

Tributyltinhydride-induced intramolecular radical cyclization to aporphines and 5-oxoaporphines

Abstract A new synthesis of aporphines by tributyltinhydride-induced intramolecular radical cyclization of bromobenzylisoquinolines is described. This route to aporphines also allowed the first total synthesis of a 5-oxoaporphine.