One-carbon homologs are structurally-related and functionally-identical organic molecules, whose chain-lengths differ by a single methylene (-CH2-) unit1. Across many classes of molecule-including pharmaceutical agents, natural products, agrochemicals, fragrances and petroleum products-the physicochemical characteristics displayed by members of a homologous series subtly differ from one compound to another, which can impart remarkable differences to their function2. The efficient generation of homologs is, therefore, an important strategy in molecular discovery programs3,4. Despite the availability of homologation strategies for several functional groups5,6, direct and general methods for one-carbon chain extension in alkenes remain an unmet synthetic need7,8. We report a catalytic one-carbon homologation process that is effective for many classes of alkene in simple and complex molecules. By leveraging the intrinsic reactivity of a novel multifaceted allyl-sulfone reagent, a streamlined one-pot process, involving cross-metathesis and a fragmentation/retro-ene cascade, formally inserts a single methylene unit to the alkene chain. Amongst applications of this process to several structurally and functionally complex molecules, we demonstrate how this practical transformation generates previously unexplored homologs of Cyclosporine-A9. These homologs show modulated pharmacological and biological properties and could provide promising leads as cyclophilin inhibitors, a target that has great potential in many disease areas10.

Five years before the 2022 multi-country mpox outbreak, Nigeria and Cameroon reported their first cases in over three decades.1,2 While Nigeria's outbreak is recognized as an ongoing human epidemic, the drivers of Cameroon's resurgence remain unclear.3,4 The rate of zoonoses remains uncertain in both countries, and gaps in genomic data obscure the timing, zoonotic and geographic origin of mpox virus (MPXV) emergence in humans. To address these uncertainties, we generated 118 MPXV genomes from Nigeria and Cameroon from 2018-2023. Our findings show that, in contrast to Nigeria, cases in Cameroon are the result of repeated zoonoses, with two distinct zoonotic lineages circulating across the Nigeria-Cameroon border. Our findings suggest that shared animal populations in the cross-border forest ecosystems drive virus emergence and spread. Accordingly, we identify the closest zoonotic outgroup to the Nigerian human epidemic lineage (hMPXV-1) in a southern Nigerian border state. We estimate that the shared ancestor of the zoonotic outgroup and hMPXV-1 circulated in animals in southern Nigeria in late 2013. We estimate that hMPXV-1 emerged in humans in August 2014 in the southern Rivers State and circulated undetected for three years. Rivers State acted as the main source of viral spread across the human epidemic. Our study sheds light on MPXV's recent establishment in the human population and highlights the risk of persistent zoonotic emergence of MPXV in the complex border regions of Cameroon and Nigeria.