Bridging the gap between natural product synthesis and drug discovery

Abstract

Various synthetic strategies have been developed to explore natural products as an enduring source of chemical information useful for probing biological relevant chemical space and impacting drug discovery.

Enzyme Kits to Facilitate the Integration of Biocatalysis into Organic Chemistry – First Aid for Synthetic Chemists

“…Of the numerous approaches for conducting a total synthesis, many were inspired by natural biosynthesis [6] . For example, the Baran group introduced the biomimetic concept of ‘two‐phase′ total syntheses of the terpenes 1 and 3 – 6 in 2009 (Figure 2A), [98] in order to make use of nature's highly efficient approach of accessing maximum diversity of natural products in a minimum number of steps by the modification of common structural scaffolds ( 3 ; Figure 2B) [99] .…”

“…[4] In the past decade, profound changes in custom paradigms of synthetic chemistry were initiated by the urgent need for sustainable industrial processes in light of the approaching climate crisis, [5] but were also fuelled by the continuous interest in the synthesis of increasingly complex natural product analogues and important industrial sectors such as drug discovery programmes. [6,7] More refined synthetic strategies such as protecting group-free [8] and biomimetic total syntheses, [9] diversity-oriented compound generation, [10,11] inert CÀ H activation, [12,13] early-or late-stage modifications, [14,15] and biocatalysis in general, [16,17] are boosting the synthetic elegance by reducing the number of steps required, increasing the atom economy, and ultimately making chemical reactions more environmentally friendly and sustainable. [18] The recent Nobel prizes in chemistry for 'asymmetric organocatalysis' [19,20] in 2021 [21] and for the 'directed evolution of enzymes' [22,23] in 2018 [24] symbolise such efforts.…”

Translational Informatics for Natural Products as Antidepressant Agents

“…For instance, TripletRes and AlphaFold are globally acclaimed contemporary two-dimensional (2D) protein structure prediction tools of deep learning, which have spectacularly boosted the efficacy of classical drug discovery strategies ( Kryshtafovych et al, 2019 ; Li et al, 2019 ; Senior et al, 2019 ). A consolidated yet thoughtful utilization of these modern computational tools will be decisive in exploring naturally occurring molecules for depression management and prognosis ( Truax and Romo, 2020 ; Woo and Shenvi, 2021 ).…”

(−)‐Isoscopariusin A, a Naturally Occurring Immunosuppressive Meroditerpenoid: Structure Elucidation and Scalable Chemical Synthesis

“…Due to the low-abundance from natural source and ambiguous structure,achemical synthesis of 1 could not only confirm all the stereocenters indubitably but also enable further biological study. [10] Due to the fascinating architectures as well as remarkable biological activities of the cyclobutane-containing natural products,anincreasing number of novel approaches targeting these unique structures have emerged. [11] Theassembly of an unsymmetrical cyclobutane ring in ac ontrolled and efficient fashion in these unique structures has long been highly desirable.…”