Total Synthesis of Spiroketal Alkaloids Lycibarbarines A–C

22 March 2023, Version 1
This content is a preprint and has not undergone peer review at the time of posting.


Lycibarbarines A–C are spirocyclic alkaloids with a unique tetracyclic framework, consisting of tetrahydroquinoline and spiro-fused oxazine-sugar spiroketal subunits. The first total syntheses of lycibarbarines A–C are reported, achieved over 10 steps (longest linear sequence) each. Through this work, it was discovered that the spiroketal unit of lycibarbarines A–C exhibits unusually high resistance to acid-mediated isomerisation and epimerisation, likely due to the basic nitrogen atom. As such, the lycibarbarines present an interesting case study of preventing the interconversion of spiroketal isomers, which may prove instructive in efforts to obtain non-thermodynamic spiroketal frameworks.


natural products
asymmetric synthesis

Supplementary materials

Supporting information
Experimental procedures, additional tables, NMR data and spectra


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.