Síntese total do alcaloide aporfioide (R)-(-)-aporfina

• Ano de defesa: 2015
• Autor(a) principal: Perecim, Givago Prado [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo
• Palavras-chave em Português: Total synthesis; Benzyne chemistry; [4 + 2] Cycloaddition reaction; Hydrogen migration; Aporphine alkaloid; (R)-(-)-aporphine; Síntese total; Química de benzino; Reação de cicloadição [4 + 2]; Migração de hidrogênio; Alcaloide aporfinoide; (R)-(-)-aporfina
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=2625876; https://repositorio.unifesp.br/handle/11600/47971

The benzyne chemistry have been successfully employed in various approaches involving total synthesis of natural products and bioactive substances. Thus, due to the considerable importance of 2-(trimethylsilyl)aryl triflates in the current context of benzyne chemistry, as well as due to the pronounced biological activities presented by aporphine alkaloids, including the potential of such compounds as agonists of dopaminergic receptors and, for instance, their anticancer, anti-HIV and antileishmanial activities, we decided to accomplish the total synthesis of the aporphine alkaloid (R)-(-)-aporphine, employing a strategy that presents a sequence of reactions, namely, [4 + 2] cycloaddition reaction followed by a hydrogen migration, which leads to the formation of the aporphine core. In this sense, we submit 1-methylene-1,2,3,4-tetrahydroisoquinoline to the reaction with benzyne, formed from 2-(trimethylsilyl)phenyl triflate, under relatively mild reaction conditions using CsF as base and MeCN as solvent. Afterwards, the key intermediate resulted from the [4 + 2] cycloaddition reaction followed by a hydrogen migration, which contains the aporphine core, was subjected to functional group transformations resulting in the aporphine alkaloid of interest (R)-(-)-aporphine, which was obtained in seven steps with an overall yield of 11%.