Nature[JOURNAL]

Carbohydrates are among the most abundant and structurally diverse biomolecules in nature, playing central roles in energy storage, molecular recognition, and cell signaling. Within this domain, C-glycosides, in which th... Carbohydrates are among the most abundant and structurally diverse biomolecules in nature, playing central roles in energy storage, molecular recognition, and cell signaling. Within this domain, C-glycosides, in which the oxygen atom of the glycosidic bond in O-glycosides is replaced by carbon, have emerged as valuable motifs in medicinal chemistry due to their resistance to enzymatic hydrolysis. Of particular importance are C-aryl glycosides, exemplified by the SGLT2 inhibitors dapagliflozin, canagliflozin, and empagliflozin, which are frontline therapies for type 2 diabetes. However, scalable syntheses of C-aryl glycosides have traditionally relied on protected sugar derivatives, lengthy sequences, or conventional cross-couplings that often suffer from poor selectivity, limited scope, and extensive protecting-group manipulation. Herein, we report a practical approach to C-aryl glycosides using glycosyl sulfonyl hydrazides as redox-neutral radical precursors for cross-coupling. Prepared directly from unprotected native sugars, these reagents generate glycosyl radicals under mild conditions and enable efficient access to diverse C-aryl glycosides, including all approved SGLT2 inhibitors, natural products such as salmochelins and neopetrosins, and medicinally relevant probes. Beyond anomeric functionalization, this platform enables C-C bond formation at multiple positions on carbohydrate scaffolds and supports stereoretentive radical coupling that can override inherent stereochemical biases, expanding practical access to carbohydrate-derived therapeutics and chemical tools.

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Stereoretentive decarbonylative C(sp)-C(sp) cross-coupling.

Huang Z, Wu T, Yuan Z … +5 more , Meng C, Garman LC, Guzei IA, Wu B, Weix DJ

Nature · 2026 Jun · PMID 42332109 · Publisher ↗

While C(sp)-C(sp) bond-forming cross-coupling methods have become more common, stereocontrolled bond-formation remains a challenge, despite its importance for drug discovery, where there is a emerging demand for molecule... While C(sp)-C(sp) bond-forming cross-coupling methods have become more common, stereocontrolled bond-formation remains a challenge, despite its importance for drug discovery, where there is a emerging demand for molecules with increased sp3 character. Enantiospecific cross-coupling approaches would complement advances in enantioselective coupling, but have been limited to specialized substrates with lower availability because stereospecific oxidative addition of more abundant chiral alkyl electrophiles is unknown. Inspired by the classic, stereoretentive Curtius rearrangement, herein we disclose a catalytic strategy that proceeds by an analogous stereoretentive decarbonylation step to form a versatile chiral alkylnickel intermediate from easily-available chiral amino-acid and α-hydroxy-acid derivatives. The chiral alkylnickel intermediates decompose and/or racemize on the order of minutes, but are sufficiently stable to enable stereoretentive cross-electrophile coupling with alkyl radicals (derived from alkyl iodides) at relatively low temperature (22-40 °C). This mechanistic strategy provides a straightforward approach to stereocontrolled C(sp)-C(sp) bond formation, including diastereomers that are inaccessible by stereoselective radical mechanisms. The "metallo-Curtius" strategy described in this study lays a mechanistic foundation for the development many new stereospecific cross-coupling reactions.

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Isotopic evidence for a cold and distant origin of 3I/ATLAS.

Cordiner M, Roth NX, Micheli M … +16 more , Villanueva G, Farnocchia D, Charnley S, Biver N, Bockelée-Morvan D, Bodewits D, Chandler CO, Crovisier J, Drozdovskaya MN, Furuya K, Kelley MSP, Milam S, Noonan JW, Opitom C, Schwamb ME, Thomas CA

Nature · 2026 Jun · PMID 42332108 · Publisher ↗

Interstellar objects provide the only directly observable samples of icy planetesimals formed around other stars, and can therefore provide insight into the diversity of physical and chemical conditions occurring during... Interstellar objects provide the only directly observable samples of icy planetesimals formed around other stars, and can therefore provide insight into the diversity of physical and chemical conditions occurring during exoplanet formation. Here we report isotopic measurements of the interstellar comet 3I/ATLAS, which reveal an elemental composition unlike any Solar System body. The water in 3I/ATLAS is enriched in deuterium, at a level of D/H = (0.98 ± 0.06)%, which is more than an order of magnitude higher than in known comets, while its range of C/C ratios (141-191 for CO and 123-172 for CO) exceeds typical values found in the Solar System, as well as nearby interstellar clouds and protoplanetary disks. Such extreme isotopic signatures indicate formation at temperatures ≲ 30 K in a relatively metal-poor environment. When interpreted with respect to models for Galactic chemical evolution, the carbon isotopic composition implies that 3I/ATLAS may have accreted as long ago as 12 billion years, following a period of intense, early star formation. 3I/ATLAS thus represents a preserved fragment of an ancient planetary system.

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