A Systematic Cheminformatics Analysis of Functional Groups Occurring in Natural Products

Abstract

The two most striking features that discriminate natural products from synthetic molecules are their characteristic scaffolds and unique functional groups (FGs). In this study we systematically investigate the distribution of FGs in natural products from a cheminformatics perspective by comparing FG frequencies in natural products with those found in average synthetic molecules. We thereby aim for the identification of FGs that are characteristic for molecules produced by living organisms. In our analysis we also include information about the natural origins of the structures investigated, allowing us to link the occurrence of specific FGs to the individual producing species. Our findings have the potential for being applied in a medicinal chemistry context concerning the synthesis of natural product-like libraries and natural product-inspired fragment collections. The results may be used also to support compound derivatization strategies and the design of “non-natural” natural products.

Analysis of the Acid/Base Profile of Natural Products from Different Sources

“…However, they all had a high proportion of acids with pK a values between 4-5 and 8-10, corresponding typically to carboxylates and phenol groups, respectively. The results are in agreement with a recent study where authors found a high prevalence of oxygen-containing functional groups in natural products, [33] and they highlight the importance of oxygen in the metabolic pathways among living species. Moreover, MEGx and UNPD showed a higher proportion of single acids with pK a values between 4-5.…”

Cheminformatics Analysis of Natural Product Scaffolds: Comparison of Scaffolds Produced by Animals, Plants, Fungi and Bacteria

“…The unique features of bacterial metabolites were also described in our recent analysis of frequency of functional groups in NPs produced by different classes of organisms. (Ertl and Schuhmann, 2019) and can to some extent be explained by an obvious tendency of bacteria to produce polyketide structures at least when cultivated at laboratory conditions. The conclusions obtained in this analysis may serve as a guide when selecting or designing scaffolds for synthesis of "non-natural" natural products (i.e.…”

Oxodealkenylative Cleavage of Alkene C(sp3)−C(sp2) Bonds: A Practical Method for Introducing Carbonyls into Chiral Pool Materials

“…In the minor pathway,t he secondary a-alkoxy hydroperoxide C is generated. Secondary alkyl hydroperoxides are prone to Fe IIcatalyzed dehydration to produce carboxylic esters (4). [22] This transformation occurs through SET from Fe II ,c leavage of the O À Obond to form the alkoxy radical intermediate,and a-hydrogen abstraction by Fe III hydroxide.A lternatively, bfragmentation of the alkoxy radical D and subsequent trapping of the alkyl radical E gives the O-alkyl TEMPO adduct 5 (which, upon oxidation, gives 2p' ').…”

“…[3] One interesting facet relevant to these contexts is the prevalence of alkenes (39.9 %), relative to that of ketones (15.9 %), enones (6.0 %), and aldehydes (2.4 %), found in natural products (Scheme 1). [4] With the chiral pool materials being useful in many types of chemical processes,as imple method for the conversion of natural alkenes into carbonyl-containing compounds would be highly valuable.In 2004, Inokuchi and Kawafuchi reported as imple protocol for the conversion of alkyl halides into carbonylcontaining compounds (Scheme 1). [5] This process involves S N 2displacement of an alkyl halide with the anion of 2,2,6,6tetramethylpiperidin-1-yl (TEMPO) and subsequent m-chloroperoxybenzoic acid (mCPBA) mediated oxidation of the Oalkyl TEMPO intermediate to give the corresponding carbonyl compound.…”