Exploring the chemical reactivity of triisopropylsilyl dialkynyl methanol for the synthesis of dialkynylcarbinol-related compounds

01 April 2024, Version 1

Abstract

Prompted by the pharmacological relevance of lipidic alkynylcarbinols, 1-(triisopropyl)silyl)penta-1,4-diyn-3-ol was exploited as a versatile C5 organic framework. Selective functionalization of this dissymmetrical dialkynylcarbinol precursor was achieved via the creation of either a Csp-Csp (alkyne), a Csp-Csp2 (alkene and aryl) or a Csp-Csp3 (RCHOH) bond. This allowed to access a novel racemic series of bioinspired acetylenic lipids that revealed amongst the most potent to date, with IC50 down to 27 nM on osteosarcoma U2OS cells. Click-type 1,3-dipolar cycloadditions such as a copper-catalyzed reaction with a long-chain alkyl azide (CuAAC) and a base-promoted reaction with a lipidic nitrile oxide were then first described in a racemic version. Preparation of both enantiomers of 1-(triisopropyl)silyl)penta-1,4-diyn-3-ol by kinetic enzymatic resolution with CAL-B immobilized on acrylic resin was carefully optimized. Finally, the use of resolved samples in 1,3-dipolar cycloaddition reactions led to the enantioenriched cycloadducts without significant epimerization of the carbinol center.

Keywords

Alkynes
Lipids
Enzymatic kinetic resolution
Carbinols
Click chemistry

Supplementary materials

Title
Description
Actions
Title
NMR spectra and LC chromatograms
Description
The file contains copies of 1H and 13C NMR spectra of all new compounds described. Chiral LC chromatograms of racemates and enantioenriched samples are also included.
Actions
Title
Experimental procedures
Description
The file contains all the experimental procedures corresponding to the reactions described in the manuscript.
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.
Comment number 3, Remi Chauvin: May 01, 2024, 22:26

This paper of shame is still online, despite previous comments and proof of a conflict of interest undeclared by alleged corresponding authors, Mrs and Mr Genisson. ChemRxiv Curators and Editors, informed several times by e-mail, are thereby alerted again.

Comment number 2, Thierry Ollevier: Apr 13, 2024, 21:44

This article is surprising in the absence of Professor Remi Chauvin’ name as a corresponding author. The reported results are part of his own results and his 10-year long running research. Both the fundamental research and the applied fields, such as medicinal chemistry with anticancer chiral dialkynylcarbinol, come from Professor Remi Chauvin’s own contributions.

Comment number 1, Remi Chauvin: Apr 10, 2024, 20:54

This post authored by former collaborators without my agreement is definitely irrelevant from both ethical and scientific standpoints. Beyond several misunderstanding of the project spirit, without any contribution to both the concept and dynamics, the two last alleged corresponding authors (Yves Genisson and his wife) have strictly no legitimacy on the initiative of this submission- with or without my name as main corresponding author at least. The project was indeed devised, rationalized, and experimentally developed in my own group until 2022. The imposture is incidentally illustrated by a recent invited talk on the topic, the abstract of which has been submitted to ChemRxiv by April 10 2024, 22:23, under the title: Lipidic Alkynyl Carbinols against Cancers and Tuberculosis, while declaring and detailing a clear conflict of interest. Remi Chauvin [email protected]