Total synthesis of twenty-five picrotoxanes by virtual library selection

03 June 2024, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

Strong-bond activation refers to the conversion of typically inert functional groups (FG) into reactive ones: e.g. C–H or C–C into C–X. Its application in retrosynthetic analysis requires evaluation of strategy (is it simplifying?) and feasibility (will it work?). However, the feasibility of strong bond cleavage can be difficult to predict due to competing low barrier pathways (e.g. 5–8 kcal/mol) in complex molecular environments. If strong bond activation can be strategically evaluated, accurately calculated and experimentally validated, it can simplify the synthesis of complex molecules. Here we build a virtual library of strategic late-stage intermediates en route to diverse picrotoxanes, calculate C–H vs. C–C oxidation preference and experimentally interrogate the predictions. Costly transition state calculations are then simplified to faster parameterizations to explain remote effects on strong bond activation and to devise concise routes to the picrotoxanes .

Keywords

total synthesis
computer-aided synthesis planning (CASP)
C–H oxidation
natural product

Comments

Comments are not moderated before they are posted, but they can be removed by the site moderators if they are found to be in contravention of our Commenting Policy [opens in a new tab] - please read this policy before you post. Comments should be used for scholarly discussion of the content in question. You can find more information about how to use the commenting feature here [opens in a new tab] .
This site is protected by reCAPTCHA and the Google Privacy Policy [opens in a new tab] and Terms of Service [opens in a new tab] apply.