Enantioselective formal synthesis of (+)-madangamine A

An enantioselective formal synthesis of the marine alkaloid madangamine A using phenylglycinol-derived lactam 1 as the starting enantiomeric scaffold is reported. The synthesis involves the construction of the C-9 substituted diazatricyclic ABC core and the final closure of D and E rings from the polyunsaturated skipped intermediate 19

Enfoques alternativos de medición de cercanía de productos. Una aplicación para la industria de General Pueyrredon

Debido a la importancia que tiene para una economía la diversificación productiva, es fundamental profundizar las investigaciones sobre la misma. Tanto a nivel país, como a nivel firma, se espera que la diversificación no siga un camino aleatorio, sino que la misma se dé hacia productos cercanos a los que ya producen. El presente trabajo se centra en el concepto de cercanía, analizando los diferentes métodos de medición de la misma. Puntualmente, se propone responder a la siguiente pregunta: ¿Qué elementos explican las diferencias detrás de los distintos enfoques de medición de cercanía de productos? Las hipótesis de trabajo son dos: i) Existen diferencias entre la cercanía de productos medida según enfoques alternativos, para el caso de las empresas industriales del partido de General Pueyrredon, y ii) Los motivos que explican dichas diferencias son: la integración vertical, el segmento de mercado, cuestiones vinculadas a la comercialización de los productos, y la marca. Las medidas de cercanía utilizadas en este trabajo serán tanto medidas basadas en nomencladores (variable categórica según la cercanía que provee la estructura de códigos, capítulos y secciones del nomenclador) como medidas de co-ocurrencia (índice de cercanía, variable continua) basadas en el principio de supervivencia. Partiendo de datos primarios y pasando por una extensiva clasificación de los pares de productos producidos en conjunto, se utilizan técnicas de análisis de correlación entre los distintos motivos de cercanía y los indicadores de la misma. Específicamente, se utilizan la prueba U de Mann-Whitney, la prueba de Kruskal-Wallis y el test Chicuadrado. Los resultados obtenidos permiten concluir que el grado de cercanía de los productos difiere significativamente según el enfoque elegido para medirla. Además, puede concluirse que el índice de cercanía es un indicador más completo, por incluir dos motivos ausentes en el enfoque tradicional: la integración vertical y la posesión de una marca.Fil: Barberis Bosch, Francisco. Universidad Nacional de Mar del Plata. Facultad de Ciencias Económicas y Sociales; Argentina.Fil: Mauro, Lucía Mercedes. Universidad Nacional de Mar del Plata. Facultad de Ciencias Económicas y Sociales; Argentina.Fil: Pretel, Federico. Universidad Nacional de Mar del Plata. Facultad de Ciencias Económicas y Sociales; Argentina

Total Synthesis of (+)-Madangamine D

Madangamines are a group of bioactive marine sponge alkaloids, embodying an unprecedented diazapentacyclic skeletal type. The enantioselective total synthesis of madangamine D has been accomplished, and represents the first total synthesis of an alkaloid of the madangamine group. It involves the stereoselective construction of the diazatricyclic ABC core using a phenylglycinol-derived lactam as the starting enantiomeric scaffold and the subsequent assembly of the peripheral macrocyclic rings. The synthesis provides, for the first time, a pure sample of madangamine D and confirms the absolute configuration of this alkaloid family

First Enantioselective Synthesis of Tetracyclic Intermediates en route to Madangamine D

The enantioselective synthesis of advanced tetracyclic precursors of madangamine D, bearing rings ABCD of this alkaloid, is reported. The saturated 14-membered ring is assembled from functionalized diazatricyclic intermediates 10 following either ring-closing metathesis or macrolactamization strategies

Unsaturated Oxazolopiperidone Lactams: an Unexpected Domino-type Double Conjugate Addition<br>cyclization Process

Reactions of 2-acetylindole enolate with unsaturated oxazolopiperidones 3, 4 and 10 unexpectedly gives pentacyclic dilactams 6, 7 and 11, respectively, resulting from a domino-type process involving two successive conjugate additions and a final cyclization

Preparation and Double Michael Addition Reactions of a Synthetic Equivalent of Nazarov Reagent

A synthetic equivalent of the Nazarov reagent, the silyl derivative 2, able to undergo base-catalyzed double Michael addition reactions with a,b-unsaturated carbonyl compounds, has been developed. The new reagent satisfactorily reacts with unsaturated indolo[2,3-a]quinolizidine lactams to give pentacyclic yohimbinone-type derivatives

Studies on the Enantioselective Synthesis of E-Ethylidene-bearing Spiro[indolizidine-1,3′-oxindole] Alkaloids

A synthetic route for the enantioselective construction of the tetracyclic spiro[indolizidine-1,3'-oxindole] framework present in a large number of oxindole alkaloids, with a cis H-3/H-15 stereochemistry, a functionalized two-carbon substituent at C-15, and an E-ethylidene substituent at C-20, is reported. The key steps of the synthesis are the generation of the tetracyclic spirooxindole ring system by stereoselective spirocyclization from a tryptophanol-derived oxazolopiperidone lactam, the removal of the hydroxymethyl group, and the stereoselective introduction of the E-ethylidene substituent by acetylation at the -position of the lactam carbonyl, followed by hydride reduction and elimination. Following this route, the 21-oxo derivative of the enantiomer of the alkaloid 7(S)-geissoschizol oxindole has been prepared

Conjugate Addition of 2-Acetylindole Enolates to UnsaturatedOxazolopiperidone Lactams: Enantioselective Access to the Tetracyclic RingSystem of Ervitsine

The stereochemical outcome of the conjugate addition reactions of 2-acetylindole enolates to unsaturated phenylglycinol-derived oxazolopiperidone lactams 1a-f is studied. After reduction of the 2-acylindole carbonyl group, the Michael adduct cis-6 underwent a Lewis acid-promoted intramolecular α-amidoalkylation, enantioselectively leading to the tetracyclic ring system of the indole alkaloid ervitsine Keywords: Lactams / Asymmetric synthesis / Cyclization / Michael addition / Heterocycle

Enantioselective Syntehsis of Alkaloids from Phenylglycinol-derived lactams

This review is focused on recent synthetic achievements and ongoing work in our laboratory using phenylglycinol-derived oxazolopiperidone lactams as starting materials for the enantioselective synthesis of piperidine-containing alkaloids: madangamines, 2,5-disubstituted decahydroquinoline and 1-substituted tetrahydroisoquinoline alkaloids, the indole alkaloids 20S- and 20R-dihydrocleavamine and quebrachamine, and indole alkaloids of the uleine and silicine groups. Keywords: alkaloids, piperidine, indole, lactams, total synthesis, phenylglycinol

A General Synthetic Route to Enantiopure 5-Substituted cis-Decahydroquinolines

A practical synthetic route to enantiopure 5-substituted cisdecahydroquinolines has been developed, the key steps being a stereoselective cyclocondensation of 2-substituted 6-oxocyclohexenepropionates 2 with (R)-phenylglycinol, the stereoselective hydrogenation of the resulting unsaturated tricyclic lactams, and the stereoselective reductive cleavage of the oxazolidine ring