New Strategies in the Efficient Total Syntheses of Polycyclic Natural Products

• DOI: 10.1021/acs.accounts.0c00531
• Publication Date: 2020-11-02T20:43:55Z
• Authors: Weilong Liu; Benke Hong; Jin Wang; Xiaoguang Lei
• Keywords: Functional group

ConspectusPolycyclic natural products are an inexhaustible source of medicinal agents, and their complex molecular architecture renders challenging synthetic targets where innovative effective approaches for rapid construction urgently required. The total synthesis polycyclic has witnessed exponential progression along with the emergence new strategies concepts, such as sequential C–H functionalizations, radical-based transformations, functional group pairing strategies. Our exerts continued interest in bioactive structurally well evaluation mode action these molecules. In this Account, we will showcase how employed guide our endeavors.During last two decades, a series remarkable advances functionalization have led to many directly functionalize bonds into useful groups. These selective transformations provided great opportunity step- atom-economical key fragments molecule synthesis. We recently furnished syntheses products: incarviatone A, chrysomycin polycarcin V, gilvocarcin V by employing multiple bond strategy. polysubstituted benzene or naphthalene skeleton was constructed through site-selective functionalizations from readily available simple starting materials, which reduced number steps streamlined synthesis.Recently, also completed skeletally diverse tetracyclic Isodon diterpenoids inspired biogenesis retrosynthetic disconnections. Radical strategically tactically utilized syntheses, reactions, including organo-SOMO catalysis, Birch reduction, regioselective 1,6-dienyne reductive cyclization, visible-light-mediated Schenck ene reaction, photoradical-mediated late-stage skeletal rearrangement, play significant roles endeavors. Protecting-group-free scalable built work achieve "ideal" Furthermore, reveals that rearrangement photo radical process is possible biological setting complement nature's carbocation chemistry product biosynthesis.Lycopodium alkaloids large family unique impressive activities. Owing fascinating architectures activities, serve inspirations community decades. To access product-like molecules exploration drug discovery, applied novel strategy furnish several Lycopodium obtained numerous compounds structural complexity comparable products.