SecoB-Type Oligomers from Pinus massonianaExpand the Procyanidin Chemical Space and Exhibit Dental Bioactivity

Investigation of a pine bark extract for bioactive proanthocyanidin oligomers resulted in the isolation of structurally related dimeric secoB-type procyanidin derivatives, 1–5. This includes scalemic mixtures of gambiriin A1 (1a) and A2 (2a) and their newly described optical antipodes, ent-gambiriin A1 (1b) and ent-gambiriin A2 (2b), respectively, as well as a racemic mixture of the newly described (ent-)gambiriin A5 (3a/3b). Furthermore, the study now fully characterizes the previously reported optically pure dimers gambiriin B1 (4) and gambirflavan D1 (5), and characterized the novel secoB-type procyanidin trimer, 6(gambirifuran C1). Thermal conversion of catechin in aqueous solution provided further evidence for the structures of 1–6and led to the purification of semisynthetic 1aand 2aas well as additional dimers 7–10. Elucidating the structures of the natural dimers, 1–5, from comprehensive NMR and ECD data and synthetic evidence provided crucial reference points for establishing the structure of the secoB-type procyanidin trimer, 6. Serving as assigned building blocks, data from the dimers supported the 3D structural assignment of 6based on NMR substituent chemical shift differences (s.c.s., syn. ΔδC) and component-based empirical ECD calculations. Within the newly characterized series of PAC-related molecules, 5exhibited high dentin biomodification potential. In addition, considering the nomenclature issues and plausible biosynthetic pathways of this group of compounds led to a consolidated nomenclature of all currently known secoB-type procyanidins. These findings, thereby, expand the chemical space of bioactive catechin oligomers, which have promise as agents for the natural enhancement of dental biomaterials. Finally, the current knowledge of the chemical space of secoB-type procyanidin derivatives was compiled to the level of absolute configuration.