Exo-selective Intramolecular (4+3) Cycloadditions to trans-Fused Perhydroazulenes: An Asymmetric Formal Synthesis of (−)-Pseudolaric acid B

05 May 2025, Version 1
This content is a preprint and has not undergone peer review at the time of posting.

Abstract

We present an asymmetric formal total synthesis of pseudolaric acid B (PAB), based on the intramolecular (4+3) cycloaddition of a new class of epoxy enolsilane substrates. This substrate type has the epoxide geminally-substituted on the tether to the furan, which reacts to yield the trans-fused perhydroazulene core of PAB containing the quaternary stereocenter. The reaction is highly diastereoselective, as opposed to cycloadditions of previous substrate types that generate the perhydroazulene framework. The role of the geminal tether in controlling the transition state conformation and the exo-selectivity is revealed by density functional theory calculations. Using this intramolecular cycloaddition as the key reaction, together with several one-pot sequences, a key intermediate in Trost’s synthesis of PAB was accomplished, representing the shortest asymmetric synthesis of this anti-tumor natural product thus far.

Keywords

pseudolaric acids
(4+3) cycloaddition
natural products
one-pot reactions
total synthesis

Supplementary materials

Title
Description
Actions
Title
Supplementary Information
Description
Supplementary Schemes and Tables, Experimental, X-ray crystallographic data, Computational details
Actions
Title
1H and 13C NMR spectra
Description
1H and 13C Spectra of compounds
Actions

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.