A cysteine-selective bioconjugation using aromatic cyclopropenium cations is reported. The reaction proceeds rapidly under aqueous conditions, enabling site-selective installation of tetrasubstituted...

We report the palladium-catalyzed synthesis of spiroindenes using oxabicycles as acetylene surrogates. This protocol allows for the synthesis of a diverse library of heterocyclic-tethered spiroindenes...

#LCSOJournalClub 209.1 (highlighted in picture) A preprint at ChemRxiv of Dorian Didier and co-workers from TU Darmstadt on a double carbon insertion on azetines to give pyridines: https://lnkd.in/e-6...

Chiral α-arylalkanoic esters, valued as anti-inflammatory agents, are synthesised through an enantioselective oxidative rearrangement of alkynes under green, metal-free conditions. This study achieves...

#LCSOSynthesisProblem is finally back after a long break! This time, Adriana challenged us to the total synthesis of (−)-Illisimonin A by Dai and co-workers. Take a look here: https://lnkd.in/eN4bRjDj...

Discovering high-affinity ligands directly from protein structures remains a key challenge in drug discovery. BindCraft is a structure-guided generative modeling platform able to de novo design miniproteins with a high affinity for a large set of targets. While miniproteins are valuable research tools, short peptides offer substantially greater therapeutic potential. However, given their lack of stabilized tertiary structures, de novo generation of functional peptides is a remarkable challenge. Here, we show that BindCraft is able to generate high affinity peptides, solely based on target structure, with remarkable success rates. For the oncoprotein MDM2, BindCraft generated 70 unique peptides; 15 were synthesized, and 7 showed specific binding with nanomolar affinities. Competition assays confirmed site-specific binding for the intended target site. For another oncology target, WDR5, six out of nine candidates bound the MYC binding WBM site with submicromolar affinity. Bindcraft’s high fidelity structure prediction enabled one shot peptide optimization via rational chemical modification, improving the potency of one WDR5 binder by 6-fold to a KD of 39 nM. BindCraft also generated candidate peptides for targeting PD-1 and PD-L1. However, none of the tested peptides showed detectable binding. Together, these results establish a first evaluation of BindCraft for peptide binder prediction. Despite remaining limitations, this tool shows the potential to rival display technologies in delivering high-affinity ligands for therapeutic development.

The discovery of new organic photocatalysts (PCs) for energy transfer (EnT) catalysis remains a significant challenge, largely due to the vast and underexplored chemical space and the delicate balance...

Cycloadditions are among the most powerful reactions for constructing molecular complexity. The archetypal example is the [4 + 2] (Diels–Alder) cycloaddition, which efficiently furnishes cyclohexene d...

#LCSOJournalClub 207.1 (Highlighted in picture) a simple selective C3-halogenation of pyridines developed by Ning Jiao, Song Song and co-workers from Peking University in Nat. Synth. https://lnkd.in/e...

This review is the next installment of an annual series that discusses the synthetic routes to access 28 small molecule drugs that were approved worldwide in 2023. A brief description of each drug’s m...

Photochemistry and total synthesis are deeply rooted in the history of organic chemistry, each developing independently while also intersecting frequently. Indeed, mild reaction conditions, versatility of transformations, and complementary selectivities to thermal methods make photochemistry an especially powerful tool for the synthesis of complex target molecules. In this Review, we highlight recent examples of total syntheses (from 2020 to 2025) featuring photochemical reactions as pivotal steps. Although the application of photochemistry in total synthesis has been consistently reviewed throughout the past decades, we feel that the wider emergence of photocatalytic methods, together with the continued importance of certain direct irradiation approaches, warrants its own discussion. We hope that our analytical approach and strategic insights will help us to identify cases where photochemical reactions could prove useful, thereby further encouraging their use in total syntheses.

Developing bioorthogonal reactions that enable investigation of biological processes is an important aim in chemical biology. Here, the authors report the malononitrile addition to azodicarboxylate (M...

Classical upconversion employs sensitizers and annihilators as two distinct molecular species and is, therefore, classified as heteromolecular. Homomolecular upconversion, the unification of both role...

Affinity-driven reactions have allowed chemists to perform site-selective modifications of native proteins. By combining the high cysteine chemoselectivity of hypervalent iodine-based ethynylbenziodox...