Structure Revision of Balsamisides A-D and Establishment of an Empirical Rule for Distinguishing Four Classes of Biflavonoids.

Balsamisides A-D ( 1 - 4 ) are anti-inflammatory and neurotrophic biflavonoidal glycosides originally proposed to possess an epoxide functionality at the C-2/C-3 position. However, there are inconsistencies in their 13 C NMR chemical shift values with those of previously reported analogs, indicating that reanalysis of NMR data for structures of 1 - 4 is necessary. Computational methods aided by the DP4+ probability technique and ECD calculations enabled structural reassignment of 1 - 4 to have a 2,3-dihydro-3-hydroxyfuran (3-DHF) instead of an epoxide. Additionally, two new biflavonoidal glycosides, balsamisides E and F ( 14 and 18 ), possessing a 2,3-dihydro-2-hydroxyfuran (2-DHF) and a 1,4-dioxane ring, respectively, were characterized by conventional NMR and MS data analysis as well as DP4+ and ECD methods. Systematic 13 C NMR analysis was performed on the four aforementioned classes of biflavonoids with a 2- or 3-DHF, epoxide, or 1,4-dioxane. As a result, diagnostic 13 C NMR chemical shift values of C-2/C-3 for rapid determination of these four biflavonoid classes were formulated, and based on this first empirical rule for (bi)flavonoids eight previously reported ones were structurally revised.