4 research outputs found
Exploration of Ring‐Closing Enyne Metathesis for the Synthesis of Azonino[5,4‐b]indoles
The use of the ring‐closing enyne metathesis (RCEYM) as a methodology for the synthesis of the azonino[5,4‐b]indole system, featuring the tricyclic substructure of the alkaloids cleavamine and quebrachamine, has been explored. Three series of enyne substrates were studied for their compatibility with the RCEYM reaction. In addition to the usual substrates bearing either a terminal or an internal alkyne, for the first time enynes with an alkynyl halide moiety were also considered. Although the metathesis cyclization allowed for assembly of the azoninoindole nucleus in all three series, an effective catalytic cycle was only noted for internal alkyne substrates. On the basis of the experimental results, the "yne‐then‐ene" pathway seems to be the mechanism at play in these reactions
Estudis exploratoris en la síntesi dels alcaloides indòlics pericina (subincanadina E) i quebrachamina emprant una estratègia unificada
[cat] Diversos alcaloides indòlics que pertanyen a famílies biogenètiques diferents es caracteritzen per presentar estructures tetracícliques amb pont constituïdes per un anell mitjà fusionat amb l'indole i una piperidina 3-substituïda. En aquest sentit, el nostre grup de recerca ha realitzat amb éxit la construcció dels sistemes tetracíclics de l'ervitsina i la 5-nor cleavamina, i la síntesi total de l'aparicina i les cleavamines utilitzant una estratègia unificada que combina dues reaccions d'eficàcia reconeguda en la formació d'enllaços C-C: una reacció de metàtesi intramolecular d'alquens (ring-closing metathesis, RCM) i una ciclació de Heck d'un halur vinílic. En la present Tesi Doctoral ens proposàrem avaluar les possibilitats sintètiques de l'estratègia de doble anulació RCM-Heck per la síntesi dels alcaloides indòlics pericina (subincanadina E) i quebrachamina. En el Capítol 2 es detallen els nostres esforços per establir una nova aproximació sintètica a l'alcaloide pericina basada en aquests conceptes. Després d'haver desenvolupat una ruta basada en reaccions de RCM de diens indòlics per accedir a estructures tricícliques que incorporen l'anell central de 9 baules característic de l'alcaloide, s'ha perseguit sense èxit la ciclació de Heck que hauria completat l'esquelet de la pericina. Al Capítol 3 es descriu la construcció d'estructures tricícliques d'azonino[5,4-b]indole substituïdes a la posició 5, com a intermedis potencials en la síntesi de l'alcaloide quebrachamina. Aquest estudi sintètic ha implicat avaluar l'ús de reaccions de RCM, tant de diens com d'enins indòlics. En concret, cal destacar la utilització d'halurs alquinílics com a substrats en la reacció de metàtesis d'enins (RCEYM) ja que, fins al present, no havien estat mai explorats per aquesta finalitat.[eng] Several indole alkaloids belonging to different biogenetic families are characterized by a bridged tetracyclic structure formed by a medium ring fused with the indole system and a 3-substituted piperidine. In this regard, our group has successfully completed the construction of the tetracyclic systems ervitsine and 5-nor cleavamine and the total synthesis of aparicine and cleavamines using a unified strategy that combines two highly recognized reactions in C-C bond formation: the ring-closing metathesis reaction (RCM) and the Heck reaction. In the present work we wanted to evaluate the synthetic possibilities of the double annulation strategy RCM-Heck for the synthesis of indole alkaloids pericine (subincanadine E) and quebrachamine. Chapter 2 details our efforts to establish a new synthetic approach to pericine alkaloid based on these concepts. Having developed an indole templated diene RCM-based route to access to the tricylic structures that incorporate the characteristic central 9-membered ring of the alkaloid, we have pursued the Heck cyclization for the completion of the pericine skeleton unsuccessfully. Chapter 3 describes the construction of tricyclic azonino[5,4-b]indole structures substituted at position 5 as potential intermediates for the synthesis of quebrachamine alkaloid. This synthetic study involved evaluating the use of RCM reactions (indole templated dienes and enynes). In particular, it is noteworthy the use of alkynyl halides as substrates for enyne metathesis reaction (RCEYM) because, up to now, they had never been explored for this purpose
Exploration of Ring‐Closing Enyne Metathesis for the Synthesis of Azonino[5,4‐b]indoles
The use of the ring‐closing enyne metathesis (RCEYM) as a methodology for the synthesis of the azonino[5,4‐b]indole system, featuring the tricyclic substructure of the alkaloids cleavamine and quebrachamine, has been explored. Three series of enyne substrates were studied for their compatibility with the RCEYM reaction. In addition to the usual substrates bearing either a terminal or an internal alkyne, for the first time enynes with an alkynyl halide moiety were also considered. Although the metathesis cyclization allowed for assembly of the azoninoindole nucleus in all three series, an effective catalytic cycle was only noted for internal alkyne substrates. On the basis of the experimental results, the "yne‐then‐ene" pathway seems to be the mechanism at play in these reactions