Chemoinformatic Characterization of NAPROC-13: A Database\nfor Natural Product <sup>13</sup>C NMR Dereplication

Natural products (NPs) are secondary\nmetabolites of natural origin\nwith broad applications across various human activities, particularly\nthe discovery of bioactive compounds. Structural elucidation of new\nNPs entails significant cost and effort. On the other hand, the dereplication\nof known compounds is crucial for the early exclusion of irrelevant\ncompounds in contemporary pharmaceutical research. NAPROC-13 stands\nout as a publicly accessible database, providing structural and <sup>13</sup>C NMR spectroscopic information for over 25 000 compounds,\nrendering it a pivotal resource in natural product (NP) research,\nfavoring open science. This study seeks to quantitatively analyze\nthe chemical content, structural diversity, and chemical space coverage\nof NPs within NAPROC-13, compared to FDA-approved drugs and a very\ndiverse subset of NPs, UNPD-A. Findings indicated that NPs in NAPROC-13\nexhibit properties comparable to those in UNPD-A, albeit showcasing\na notably diverse array of structural content, scaffolds, ring systems\nof pharmaceutical interest, and molecular fragments. NAPROC-13 covers\na specific region of the chemical multiverse (a generalization of\nthe chemical space from different chemical representations) regarding\nphysicochemical properties and a region as broad as UNPD-A in terms\nof the structural features represented by fingerprints.