Franco Marcelo S, Silva Rodrigo C, Rosa Gabriel H S, Flores Lara M, de Oliveira Kleber T, de Assis Francisco F
Department of Chemistry, Universidade Federal de Santa Catarina, Campus Universitário Trindade, Florianópolis, Santa Catarina 88040-900, Brazil.
Department of Chemistry, Universidade Federal de São Carlos, Rodovia Washington Luis km 235, São Carlos, São Paulo 13565-905, Brazil.
ACS Omega. 2023 Jun 14;8(25):23008-23016. doi: 10.1021/acsomega.3c02134. eCollection 2023 Jun 27.
An original total synthesis of the antiepileptic drug brivaracetam (BRV) is reported. The key step in the synthesis consists of an enantioselective photochemical Giese addition, promoted by visible-light and the chiral bifunctional photocatalyst Δ-. Continuous flow conditions were employed to improve the efficiency and allow an easy scale-up of the enantioselective photochemical reaction step. The intermediate obtained from the photochemical step was converted into BRV by two different pathways, followed by one alkylation and amidation, thus giving the desired active pharmaceutical ingredients (API) in 44% overall yield, 9:1 diastereoisomeric ratio (dr) and >99:1 enantiomeric ratio (er).
报道了抗癫痫药物布立西坦（BRV）的首次全合成。该合成的关键步骤包括由可见光和手性双功能光催化剂Δ-促进的对映选择性光化学吉泽加成反应。采用连续流动条件以提高效率并便于对映选择性光化学反应步骤的放大。通过两种不同途径将光化学步骤得到的中间体转化为BRV，随后进行一次烷基化和酰胺化反应，从而以44%的总收率、9:1的非对映异构体比例（dr）和>99:1的对映体比例（er）得到所需的活性药物成分（API）。
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