Seco B-Type Oligomers from Pinus massoniana Expand the Procyanidin Chemical Space and Exhibit Dental Bioactivity

Abstract

Investigation of a pine bark extract for bioactive proanthocyanidin oligomers resulted in the isolation of structurally related dimeric seco B-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 seco B-type procyanidin trimer, 6 (gambirifuran C1). Thermal conversion of catechin in aqueous solution provided further evidence for the structures of 1−6 and led to the purification of semisynthetic 1a and 2a as 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 seco B-type procyanidin trimer, 6. Serving as assigned building blocks, data from the dimers supported the 3D structural assignment of 6 based on NMR substituent chemical shift differences (s.c.s., syn. Δδ C ) and component-based empirical ECD calculations. Within the newly characterized series of PACrelated molecules, 5 exhibited 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 seco B-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 seco B-type procyanidin derivatives was compiled to the level of absolute configuration.

Research progress of procyanidins in repairing cartilage injury after anterior cruciate ligament tear

“…As one of the most consumed polyphenols in the human diet, procyanidin is formed by the polymerization of catechins, epicatechins, and epicatechin gallates, with the basic structural unit being a flavan-3-ol [ [18] , [19] , [20] ]. Procyanidin can be extracted from sources such as grape seeds, peanut skins, persimmon peels, apples, hawthorn, pine bark, and tea leaves [ [21] , [22] , [23] , [24] , [25] , [26] ]. Procyanidin was first discovered and isolated from peanut seed coats by Masquelier, and subsequently, the understanding of the procyanidin family has evolved through ongoing research efforts.…”

Perplexing Polyphenolics: The Isolations, Syntheses, Reappraisals, and Bioactivities of Flavonoids, Isoflavonoids, and Neoflavonoids from 2016 to 2022

“…Compounds 144–147 are seco B-type procyanidin dimers, with compounds 144 and 145 optical antipodes of gambiriin A1 and A2, respectively. Similarly, compounds 146 and 147 are a pair of optical antipodes, while compound 148 is the first seco B-type procyanidin trimer [ 60 ].…”

“…From the isolates, compounds 1 , 10 , 27–34 , 55 , 79 , 81 , 148 , 227 , 228 , 248 , and 249 were not tested for unspecified reasons [ 19 , 25 , 31 , 38 , 41 , 60 , 76 , 79 ]. Additionally, compound 82 was not tested due to the putative inactivity of flavanonols in the antigen-induced degranulation assay in RBL-2H3 cells [ 42 ].…”

“…The racemic mixtures were tested for their dental activities, and all three significantly increased the complex modulus of dentin by 3.3-fold. However, the differences in the bioactivity of the enantiomers (if any) could not be determined [ 60 ].…”