PhD Scientific Days 2026

Pharmaceutical Sciences and Health Technologies 2.

Breaking Technological Limits in HT Synthesis: A Platform Concept to Unlock Phase-Transfer Catalysis in Microplate-Based SN2 Automation

Előadó neve

Mr. Csik, Soma

Neptune code

QWHCH2

Előadó munkahelye

Semmelweis Egyetem Gyógyszerészi Kémiai Intézet

Előadó telefonszáma

06303791646

Előadó e-mail címe

csik.soma@stud.semmelweis.hu

Az előadás címe

Breaking Technological Limits in HT Synthesis: A Platform Concept to Unlock Phase-Transfer Catalysis in Microplate-Based SN2 Automation

Szerző(k) neve és munkahelye

Soma Csik¹

1: Semmelweis Egyetem Gyógyszerészi Kémiai Intézet

Bemutatás módja

Szóbeli

Szekció

Pharmaceutical Sciences and Health Technologies 2.

Language of the presentation

Hungarian

Preferred session

Pharmaceutical Sciences and Health Technologies

Összefoglaló szövege

Inroduction
Microplate-based reactions used in high throughput synthesis face significant challenges: the sub-optimal mixing of biphasic systems, the low solubility of nucleophiles, and the lack of automation of the purifications steps. Classical phase transfer catalysts (PTC) can not be efficiently integrated homogenously on microplate-based automated synthesis platforms, therefore we require a new approach.
Aims
Our aim was to build a new generation PTC platform, which is robust, regenerable, and makes biphasic SN2 reactions on an automated microplate systems possible.
Method
96 well microplate compatible vials were treated with HF, after which bidenzo-18-crown-6-ether was covalently immobilized onto the vials' surface through a 3-chloropropyltriethoxysilane linker (functionalisation: 0,4 ± 0,1 µmol/well). The activity of the catalyst was investigated with an SN2 model reacion (BnCl + KCN or NaSCN). The reactions were carried out at 30°C and 300 rpm shaking, and were evaluated using HPLC-MS, and isolated yield.
Results
Without a catalyst, the conversion was merely 28% (KCN) and 11-9% (NaSCN), with homogenous catalyst, a slight improvement was observed (30% conversion, 24% yield), with the covalently immobilized PTC, however, we reached 100% coversion under 12 hours, and yields reached 86% (KCN) and 80% (NaSCN). The system reamined witihin 5% of its original activity through 5 consequitve runs. The standard deviation across vials were under 10%, which signals good reproducibiliy
Conclusion
The developed, crown ether based, covalently immobilized PTC platform is able to overcome the technological challenges presented by microplate-based two phase synthesis. The platform is waste free, does not require purification, and considerably boosts the rate of biphasic SN2 reacions. This catalyst system can be integrated into any liquid handling station and broadens the scope of early phase drug discovery and aids the building of chemical libraries by making the synthesis of so far impossible compounds possible.
Funding
This work was supported by University Research Fellowship Program ofthe Ministry for Culture and Innovation from the source of the NationalResearch, Development, and Innovation Fund (Grants EKÖP-24-4-II-BME-63 and EKÖP-25-4-II-BME-136)

University

Semmelweis University

Supervisor

Dr. Golcs Ádám

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

before finishing undergraduate studies (TDK, MD-PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

jóváhagyta

Előadó

9716

Start

09:45

End

09:55