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To mark the occasion of Nature Chemistry turning 10 years old, we asked scientists working in different areas of chemistry to tell us what they thought the most exciting, interesting or challenging aspects related to the development of their main field of research will be — here is what they said.

Molecular editing allows structures to be built up in terms of complexity, or changed or pruned one atom at a time using transformations which are mild and selective enough to be employed at the late stages of a synthetic sequence. In this Review, a subclass of molecular editing reactions termed ‘single-atom skeletal editing’ are described, with a particular focus on heterocycles.

Strategies that utilize the oxidation of unactivated C–H bonds are becoming increasingly popular in natural product total synthesis. This Review classifies and highlights the different strategic use-cases of oxidation reactions as they were applied in recent total syntheses.

A versatile intermediate has been shown to provide access to a wide variety of compounds in the cortistatin family. This approach offers the most efficient total synthesis of the cortistatins reported so far.

The silver-mediated deconstructive functionalization of saturated nitrogen heterocycles via acylic haloamine intermediates provides access to various acyclic amines as well as enabling ring contraction and skeletal remodelling.

Through the bio-engineering of Saccharomyces cerevisiae high titres of artemisinic acid were produced using a novel cytochrome P450 monooxygenase. Optimization of this process on an industrial scale may significantly reduce the cost of artemisinin, which could then be used to combat malaria in resource-poor settings.

Quantifying molecular complexity has the potential to enhance retrosynthetic analysis and, thus, aid the development of efficient total syntheses. This Perspective discusses methods for rigorous, reproducible complexity measurement, highlighting their potential to revolutionize traditional complex molecule synthesis and uncover new synthetic opportunities.

Natural product chemistry remains critical to the discovery of small molecules that possess unique bioactivities. A collaborative approach to studying the phomactin diterpenoid family that spans isolation, chemical synthesis and investigation of their bioactivity is now reported. The novel congeners that were isolated inspired a divergent strategy to achieve their practical preparation and their anti-tumour evaluation.

Many natural products exist as families of structurally similar molecules, and therefore developing skeletal modifications of common intermediates offers flexible and powerful approaches for target synthesis. Here, the authors report a single-atom insertion into the framework of the benzenoid subfamily, providing access to the troponoid congeners.

Generating strategies that use modern synthetic methods to access privileged chemical space is a central goal of total synthesis. Now, a strategy that is orthogonal to classic approaches, coupled with C–H functionalization methods, leads to the shortest synthesis of the sesquiterpenoid longiborneol and divergent syntheses of oxygenated longiborneol congeners.

The biosynthesis of secondary metabolites such as stephacidin A and its congeners continues to intrigue both biochemists and synthetic chemists. Now, a laboratory chemical synthesis of these natural products has been achieved based on a bioinspired synthetic strategy, which may provide key insights into the possible biosynthesis of these captivating molecules.

Natural products citrinalin B and cyclopiamine B, which contain basic nitrogen atoms that are susceptible to oxidation during synthesis, can be synthesized by the selective introduction and removal of functional groups.

A hydrindanone-based approach to yohimbinoid natural products has been developed. A judicious choice of reaction conditions — inspired by prior work by the Stork group — allows effective control of the stereochemistry at C3 of the yohimbinoid skeleton. This approach has resulted in the first total syntheses of the C3 epimeric natural products venenatine and alstovenine.

While 2000-2019 Snow Water Availability increased, nearly 3% of Canada and Alaska, particularly in the North American Cordillera, underwent significant losses. Along with other insignificant losses, water supply for 86% of Canadians is threatened.

In Pseudoalteromonas rubra, an unclustered biosynthetic gene encodes a di-iron oxygenase-like enzyme that catalyzes regiospecific C–H activation and cyclization of prodigiosin, yet is unrelated to the Rieske oxygenases that produce other cyclized prodiginines.

This Primer provides an overview of the best practices for C–H activation as well as key advances in asymmetric, photoinduced and electrocatalytic-mediated catalysis for this synthetic platform. An overview of how C–H activation facilitates the synthesis of molecules such as structurally complex (bio)polymers and drugs is provided along with the current challenges and priorities for the next decade.

This Primer summarizes the most relevant aspects of chemical synthesis in this information age for those looking to understand the software, hardware and data and how these are used to enable retrosynthetic logic, reaction prediction and automation.