Biomimetic and Natural Product Synthesis

Abstract

Inspired or learning from nature is always a great approach to solve problems. In terms of natural product synthesis, which is always challenging, it is wise to imitate nature’s way to overcome difficulty. Biomimetic synthesis has been recognized for its remarkable ability to simplify the synthetic processes toward complex natural targets. In this Thieme Cheminar, our speakers will discuss their recent results in this field.Biomimetic Catalyst Systems from the Self-assembly of AmphiphilesCooperative interactions between precisely positioned functional groups in an active site are one of the hallmarks of natural enzymes. Taking this queue from biological systems, chemists have devised numerous strategies for the pre-organization of functional groups to allow the formation of multiple contacts with a bound substrate. Recently, we demonstrated that such cooperative interactions can also be achieved within self-assembled vesicles. In this talk, we will discuss how self-assembly offers a dynamism that allows the incorporation of stimuli-responsiveness into these systems and even life-like properties.Current challenges in this research area include the design of structures where its formation and destruction can be reversibly coupled to an external stimulus (e.g. chemical fuel or light), systems that operate out of equilibrium, and the demonstration of communication between components within a chemical network (e.g. via feedback loops). The incorporation of responsive components within chemical networks can lead to new systems/materials that are self-generating, self-repairing and with the potential to display adaptive and evolutive properties.Chemical Emulation of the Biosynthesis of Natural ProductsBiomimetic synthesis is an effective strategy to streamline the synthesis of structurally complex bioactive natural products. However, the biosynthetic pathways of skeleton rearranged natural products are not disclosed yet in most cases. We developed a biosynthetic network analysis (BNA) method to address this general issue. By taking advantage of this method, we accomplished the divergent total syntheses of pentacyclic cytochalasans and merocytochalasans from a common precursor aspochalasin D based on biosynthetic network analysis of the cytochalasans biosynthetic pathways. The key steps of the syntheses include Prins-type and ene-type cyclizations to establish the core of pentacyclic aspochalasans. Here we report a bioinspired modular synthesis of merocytochalasans by taking advantage of a biomimetic [5+2] heterocycloaddition of an ortho-quinone intermediate. The synthetic efforts provide a platform for the synthesis of more than 500 valuable cytochalasans bearing different macrocycles and amino-acid residues. Furthermore, we realized the efficient synthesis of triterpene spirochensilide A from lanosterol through the chemical emulation of its biosynthetic pathway.Applications of Quantum Chemistry in Biomimetic Syntheses of Polycyclic Furanocembrane DerivativesThis talk summarizes the guidance provided by quantum chemical calculations to the biomimetic syntheses of polycyclic marine furanocembrane derivatives. Polycyclic furanocembrane derivatives are a group of structurally complex and biologically important marine natural products isolated from marine corals. Their syntheses are challenging due to their structural complexity. Biomimetic synthetic proposals have been made and some verified via chemical synthesis. Computational chemistry can support these biomimetic syntheses. In this talk, we would like to share the synthetic and computational attempts we have made in the biomimetic syntheses of polycyclic furanocembrane derivatives, including intricarene, bielschowskysin, providencin and plumarellide.