https://onlinelibrary.wiley.com/doi/pdf/10.1002/ejoc.201601485

Hydrogen Atom Transfer (HAT): A Versatile Strategy for Substrate Activation in Photocatalyzed Organic Synthesis

Many naturally occurring substances, traditionally used in popular medicines around the world, contain the coumarin moiety. Coumarin represents a privileged scaffold for medicinal chemists, because of its peculiar physicochemical features, and the versatile and easy synthetic transformation into a large variety of functionalized coumarins. As a consequence, a huge number of coumarin derivatives have been designed, synthesized, and tested to address many pharmacological targets in a selective way, e.g., selective enzyme inhibitors, and more recently, a number of selected targets (multitarget ligands) involved in multifactorial diseases, such as Alzheimer’s and Parkinson’s diseases. In this review an overview of the most recent synthetic pathways leading to mono- and polyfunctionalized coumarins will be presented, along with the main biological pathways of their biosynthesis and metabolic transformations. The many existing and recent reviews in the field prompted us to make some drastic selections, and therefore, the review is focused on monoamine oxidase, cholinesterase, and aromatase inhibitors, and on multitarget coumarins acting on selected targets of neurodegenerative diseases.

Coumarin: A Natural, Privileged and Versatile Scaffold for Bioactive Compounds

The divergent total syntheses of complex natural products from a common intermediate have attracted enormous attention in the chemical community in the past few years because it can improve the efficiency of chemical synthesis. A number of powerful and unified strategies have been developed by emulating the natural biosynthesis or through innovative transformations. This review focuses on the total synthesis of natural products by applying divergent strategies and the literature covering from 2013 to June 2017. On the basis of where the diversity comes from, the examples are grouped into three parts and discussed in detail. In each group, the examples that synthesize natural products belonging to the same subfamily are put together to contrast with one another.

Divergent Strategy in Natural Product Total Synthesis.

Recent advances in radical transformations of internal alkynes

A direct hydroalkylation of disubstituted alkynes with unfunctionalized ethers and amides was achieved in an atom-efficient and additive-free manner through the synergistic combination of photoredox and nickel catalysis. The protocol was effective with a wide range of internal alkynes, providing products in a highly selective fashion. Notably, the observed regioselectivity is complementary to conventional radical addition processes. Mechanistic investigations suggest that the photoexcited iridium catalyst facilitated the nickel activation via single-electron transfer.

Photoinduced Nickel-Catalyzed Chemo- and Regioselective Hydroalkylation of Internal Alkynes with Ether and Amide α-Hetero C(sp3)–H Bonds

Visible-Light-Promoted Dual C-C Bond Formations of Alkynoates via a Domino Radical Addition/Cyclization Reaction: A Synthesis of Coumarins.

Bioinspired Collective Syntheses of Iboga-Type Indole Alkaloids

Protecting-Group-Free Total Synthesis of (−)-Lycopodine via Phosphoric Acid Promoted Alkyne Aza-Prins Cyclization

(3 + 2)-Annulation of p-Quinamine and Aryne: A Strategy To Construct the Multisubstituted Hydrocarbazoles.

The first bioinspired total syntheses of (-) kravanhins A and C were accomplished from a labdane diterpenoid derivative. The key reactions involve a photooxidation and a one-pot sequential aldol cyclization and lactonization, which provide a new plausible biosynthetic pathway for the kravanhins and other symbiotic members.

Zhuliang Zhong

Papers

Visible-Light-Promoted Dual C-C Bond Formations of Alkynoates via a Domino Radical Addition/Cyclization Reaction: A Synthesis of Coumarins.

Bioinspired Collective Syntheses of Iboga-Type Indole Alkaloids

Protecting-Group-Free Total Synthesis of (−)-Lycopodine via Phosphoric Acid Promoted Alkyne Aza-Prins Cyclization

(3 + 2)-Annulation of p-Quinamine and Aryne: A Strategy To Construct the Multisubstituted Hydrocarbazoles.

Bioinspired Total Syntheses of Isospongian-type Diterpenoids (-)-Kravanhins A and C.