Conditional Molecular Generation Net Enables Automated Structure Elucidation Based on <sup>13</sup>C NMR Spectra and Prior Knowledge
Lin Yao, Minjian Yang, Jianfei Song, Zhuo Yang, Hanyu Sun, Hui Shi, Xue Liu, Xiangyang Ji, Yafeng Deng, Xiaojian Wang
Abstract
Structure elucidation of unknown compounds based on nuclear magnetic resonance (NMR) remains a challenging problem in both synthetic organic and natural product chemistry. Library matching has been an efficient method to assist structure elucidation. However, it is limited by the coverage of libraries. In addition, prior knowledge such as molecular fragments is neglected. To solve the problem, we propose a conditional molecular generation net (CMGNet) to allow input of multiple sources of information. CMGNet not only uses 13 C NMR spectrum data as input but molecular formulas and fragments of molecules are also employed as input conditions. Our model applies large-scale pretraining for molecular understanding and fine-tuning on two NMR spectral data sets of different granularity levels to accommodate structure elucidation tasks. CMGNet generates structures based on 13 C NMR data, molecular formula, and fragment information, with a recovery rate of 94.17% in the top 10 recommendations. In addition, the generative model performed well in the generation of various classes of compounds and in the structural revision task. CMGNet has a deep understanding of molecular connectivities from 13 C NMR, molecular formula, and fragments, paving the way for a new paradigm of deep learning-assisted inverse problem-solving.