All three A-type IFLs were assigned as 2O7/48 via NOESY correlations (Figure ) from H-4 (rings C, I, and O) to H-2 (rings F, L, and R), as well as a strongly positive Cotton effect in the region 220~240 nm (Figure ). Pinuspirotetrin (2) represents the first heterodimeric framework in any PAC, consisting of a spirotype dimer (2a) and an A-type dimer (5). Scheme 1 shows a plausible biosynthetic pathway for 2, which rationalizes the spiro dimer 2a as resulting from intermediates (iii2a) via oxidative flavanone-flavonol conversion. While all isolates stemmed from a bioactive fraction, only 3 could be evaluated for dentin bioactivity due to limited yields. Hexamer 3 increased the modulus of elasticity of dentin by 4.3-fold, a value between those of A-type dimers (4-7) and the most highly potent trimer and tetramers. This further supports the overall hypothesis that medium-size (n = 3 and 4) PACs elicit the highest increase in key mechanical properties of dentin. These enhancements to the dentin have promising therapeutic application for the development of novel dental biomaterials. A comprehensive structure and bioactivity relationships of PACs will be reported in due course. While the structural novelties of 1 and 2, and the unusual size and complexity of 3 did not infer bioactivity in the dentin bioassays, they contribute valuable SAR information and expand the 3D chemical diversity space of condensed tannins.