Applications of transition state calculations in the key cyclization of small molecule natural product synthesis

Rongxiang Qiu,J Sun,Z Li,X Liu

doi:10.1051/e3sconf/202129001024

Abstract

The diversification of the conformation and configuration of the carbocyclic skeleton of natural products is an important reason for the diversity and complexity of the structure of natural products. The corresponding cyclization synthesis has attracted much attention. Computational chemistry approaches have the advantages of non-toxic, harmless and relatively low cost, and they are increasingly used to model and understand molecular phenomena. The reaction mechanism and thermodynamic parameters determine the feasibility of the cyclization and the enantioselectivity of the cyclization products. The transition state calculations can provide these thermodynamic parameters, which helps to elucidate the cyclization mechanism, calculate the reaction rationality, predict the performance of the new synthesis method and provide a basis for the comprehensive synthesis design.

Highlights

Natural products are an important source of drugs and lead compounds as usually have unique structures and the ability to bind to specific targets
In the early 20th century, computational chemistry approaches were introduced into the synthesis of natural products to model molecular structures and interpret experimental results
[7] Chromodorolide is one of the diterpenoids, and it was reported that the chromodorolides have the in vitro nematocidal, antitumor, and antimicrobial activities

Summary

Introduction

Natural products are an important source of drugs and lead compounds as usually have unique structures and the ability to bind to specific targets. Avoiding the difficulty in extraction and separation, high cost and the ecosystem destruction, artificially synthesized natural products have gradually emerged and attracted much attention. In the early 20th century, computational chemistry approaches were introduced into the synthesis of natural products to model molecular structures and interpret experimental results. [1] With the development of computing technology, the calculation accuracy continues to improve, and the calculation model continues to diversify. [2] Appropriate calculation methods are employed to investigate various chemical and physical properties through molecular mechanics, ab initio calculations, semi-empirical and hybrid methods. A few decades ago, a typical transition state calculation would require months to run, in generally, while the same calculation just takes a few seconds. [2] Appropriate calculation methods are employed to investigate various chemical and physical properties through molecular mechanics, ab initio calculations, semi-empirical and hybrid methods. [2,3,4] It is more and more helpful and meaningful for the comprehensive synthesis design

Elucidating mechanism and predicting reactivity

Findings

Conclusion and prospects