shenvi.bsky.social (@shenvi.bsky.social)

Congrats to Dylan and Stephen for their paper on diverse glycosylations of cotylenol en route to 14-3-3 molecular glues. This work was expedited by autoDFT, a Python script that Stephen wrote to convert SMILES to DFT-optimized structures (and ensembles of conformers).

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Contrasteric Glycosylations of Cotylenol and 1,2-Diols by Virtual Linker Selection Many terpene glycosides exhibit contrasteric patterns of 1,2-diol glycosylation in which the more hindered alcohol bears a sugar; protection of the less hindered alcohol only increases steric repulsion. Here, we report a method for contrasteric glycosylation using a new sugar-linker that forms a cleavable, 10-membered ring with high efficiency, leading to syntheses of cotylenin E, J, and ISIR-050. Linker selection was aided by DFT calculations of side reactions and stereoselectivity, as well as conformational analyses using autoDFT, a Python script that converts SMILES strings to DFT-optimized conformational ensembles. https://pubs.acs.org/doi/epdf/10.1021/jacs.4c15719?ref=article_openPDF