Modular, Scalable Total Synthesis of Lapparbin

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


This work reports the development of a novel synthetic approach for the highly strained atrop-Tyr C-6-to-Trp N-1' linkage, which can be executed on a decagram scale using a modular strategy involving Pd-catalyzed C-H biarylation followed by Larock macrocyclization. Moreover, the first total synthesis of lapparbin (1) was achieved by applying this synthetic strategy. Furthermore, the modular synthesis utilizing C-H biarylation and Larock macrocyclization, discovered in the total synthesis of lapparbin (1), was demonstrated to be applicable to various arbitrary biaryl linkages, including non-natural types.


C-H activation
Total Synthesis

Supplementary materials

Supporting Information
Experimental Procedures and Characterization of Compounds


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.