Ring systems in natural products: structural diversity, physicochemical properties, and coverage by synthetic compounds

Abstract

This cheminformatics study investigates the ring systems present in natural products and their coverage by ring systems observed in synthetic compounds.

Scaffold Generator: a Java library implementing molecular scaffold functionalities in the Chemistry Development Kit (CDK)

“…The core results of this showcase analysis comparing the most frequent NP and drug molecule scaffolds (i.e. commonness of benzene, oxygen as the dominant hetero atom in NP, nitrogen in drug molecules) are in general agreement with similar studies [ 15 , 19 , 74 – 76 ]. A significantly higher prevalence of aromatic scaffolds in drug molecules as opposed to NP that most of these studies report cannot be observed here.…”

Scaffold Generator - A Java library implementing molecular scaffold functionalities in the Chemistry Development Kit (CDK)

“…The core results of this showcase analysis comparing the most frequent NP and drug molecule scaffolds (i.e. commonness of benzene, oxygen as the dominant hetero atom in NP, nitrogen in drug molecules) are in general agreement with similar studies [15,19,[74][75][76]. A significantly higher prevalence of aromatic scaffolds in drug molecules as opposed to NP that most of these studies report cannot be observed here.…”

“…Another application of scaffold-based methods is identifying privileged substructures in active molecules or NP that can be used as lead structures in the development of new drugs [5,[13][14][15][16][17][18][19]. Within NP chemical space, macrocyclic structures or cyclic peptides are of specific interest for these medicinal chemistry purposes [20][21][22][23].…”

Dearomative ring expansion of thiophenes by bicyclobutane insertion

“…C yclic organic compounds, especially heterocycles, play a key role in pharmaceutical and natural products chemistry, as well as materials science (1)(2)(3). Ring architecture not only influences properties such as lipophilicity, three dimensionality, and scaffold rigidity but also determines molecular function and reactivity (1)(2)(3). Hence, the development of methods to precisely form and manipulate ring systems is of utmost importance in synthetic chemistry.…”

“…The hetero(bi)cyclic moiety is the basic scaffold of numerous important biologically active natural products ( 3 , 20 , 21 ). Insertion of C(sp 3 )-rich rings into heterocycles to form bicyclic compounds is appealing because sp 3 richness, three dimensionality, and increased conformational rigidity often facilitate the successful design of new drugs ( 1 ).…”