Overriding Innate Decomposition Temperatures of an Avibactam Prodrug Precursor Using Data Science-Guided Synthesis

IF 3.1 3区化学 Q2 CHEMISTRY, APPLIED

Organic Process Research & Development Pub Date : 2024-04-10 DOI:10.1021/acs.oprd.4c00044

Jacob Werth*, Michael Butler, Jenson Verghese, Nga M. Do, Lacey Samp, Remzi Duzguner and Michele T. Buetti-Weekly,

引用次数: 0

Abstract

Statistical analysis is used to correlate the thermal decomposition temperature of diverse leaving groups of an avibactam prodrug precursor. SMILES strings and Mordred calculated parameters were leveraged to provide a time-efficient workflow for model development. The resulting models were deployed to predict a novel analogue with a higher onset temperature, allowing for an overall safer reagent and proof of concept for the workflow. Interpretation of the descriptors featured in the models and subsequent DFT analysis uncovered univariate trends, providing a deeper understanding of the decomposition pathway. Finally, this workflow enabled the development of a predictive model correlating energy output of the precursor analogs for a more comprehensive assessment.

Abstract Image

查看原文本刊更多论文

利用数据科学指导合成，超越阿维巴坦原药前体的先天分解温度

统计分析用于关联阿维巴坦原药前体不同离去基团的热分解温度。利用 SMILES 字符串和 Mordred 计算参数为模型开发提供了一个省时高效的工作流程。由此产生的模型被用于预测一种起始温度较高的新型类似物，使试剂总体上更加安全，并证明了工作流程的概念。对模型中描述符的解释和随后的 DFT 分析揭示了单变量趋势，加深了对分解途径的理解。最后，通过该工作流程，开发出了与前体类似物能量输出相关联的预测模型，以进行更全面的评估。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Organic Process Research & Development 化学-应用化学

CiteScore

6.90

自引率

14.70%

发文量

251

审稿时长

2 months

期刊介绍： The journal Organic Process Research & Development serves as a communication tool between industrial chemists and chemists working in universities and research institutes. As such, it reports original work from the broad field of industrial process chemistry but also presents academic results that are relevant, or potentially relevant, to industrial applications. Process chemistry is the science that enables the safe, environmentally benign and ultimately economical manufacturing of organic compounds that are required in larger amounts to help address the needs of society. Consequently, the Journal encompasses every aspect of organic chemistry, including all aspects of catalysis, synthetic methodology development and synthetic strategy exploration, but also includes aspects from analytical and solid-state chemistry and chemical engineering, such as work-up tools，process safety, or flow-chemistry. The goal of development and optimization of chemical reactions and processes is their transfer to a larger scale; original work describing such studies and the actual implementation on scale is highly relevant to the journal. However, studies on new developments from either industry, research institutes or academia that have not yet been demonstrated on scale, but where an industrial utility can be expected and where the study has addressed important prerequisites for a scale-up and has given confidence into the reliability and practicality of the chemistry, also serve the mission of OPR&D as a communication tool between the different contributors to the field.