Total Synthesis as a Vehicle for Collaboration

Abstract

Collaboration" is not the first word most would associate with the field of total synthesis. In fact, the spirit of total synthesis is all-too-often reputed as being more competitive, rather than collaborative, sometimes even within individual laboratories. However, recent studies in total synthesis have inspired a number of collaborative efforts that strategically blend synthetic methodology, biocatalysis, biosynthesis, computational chemistry, and drug discovery with complex molecule synthesis. This Perspective highlights select recent advances in these areas, including collaborative syntheses of chlorolissoclimide, nigelladine A, artemisinin, ingenol, hippolachnin A, communesin A, and citrinalin B. The legendary Woodward−Eschenmoser collaboration that led to the total synthesis of vitamin B 12 is also discussed.

Metal-Catalyzed C–H Bond Oxidation in the Total Synthesis of Natural and Unnatural Products

“…Hippolachin A was also evaluated to be a potential agent in the treatment of Cryptococcus neoformans infections. 79 Having accomplished the total synthesis of (+)-hippolachin A independently, the research groups of Wood and Brown decided to work in collaboration 80 to obtain an optimal route towards (±)-hippolachin A (131). The collaborative route constituted of the early stages of the Brown synthesis and the endgame of the Wood route.…”

Pharmacophore-Directed Retrosynthesis Applied to Rameswaralide: Synthesis and Bioactivity of Sinularia Natural Product Tricyclic Cores

“…Furthermore, intermediates 15 and 19 were readily transformed into three additional analogues 31 – 33 to provide additional SAR data (see the SI for synthetic details). In collaboration with Stoltz’s group, three additional tricyclic analogues 34 – 36 were assayed to widen the SAR profile…”

“…Furthermore, intermediates 15 and 19 were readily transformed into three additional analogues 31− 33 to provide additional SAR data (see the SI for synthetic details). In collaboration with Stoltz's group, 51 three additional tricyclic analogues 34−36 were assayed to widen the SAR profile. 52 Cell viability assays (alamar blue viability assay, 72 h incubation) employing three cancer cell lines were performed with the described simplified Sinularia natural product derivatives (Table 1).…”

Síntese total do (+)-raputindol A

“…O núcleo indólico é encontrado em fármacos empregados no tratamento de diversas doenças, como será exemplificado na sequência. O sertindol (14) é um fármaco que atua nos receptores de dopamina D2, serotonina 5-HT2, 5-HT2C e a-adrenérgicos, utilizado para tratamento de doenças do sistema nervoso central principalmente como antipsicótico para o tratamento de esquizofrenia e outras psicoses, alucinações, desordens bipolares e ansiedade severa, dentre outros problemas de ordem psicótica (figura 4). sintéticos.…”

“…13 Pode-se ainda considerar a síntese total como um veículo para a colaboração entre grupos de pesquisa. 14 Algumas possibilidades são parcerias com estudos teóricos (para elucidar mecanismos de reação ou guiar a escolha do estereoisômero mais provável, por exemplo, no caso em que a configuração absoluta ainda não está estabelecida)), emprego de biocatálise, estudos de biossíntese, ecologia e biologia química, aplicação da química em fluxo e colaborações com outros grupos de síntese que desenvolvam metodologias sintéticas. Deste modo, a cooperação entre pesquisadores pode enriquecer o trabalho e expandir as fronteiras do conhecimento.…”