d‑chiro-Inositol Derivatives with Multidrug Resistance Reversal Activities from the Fruits of Chisocheton siamensis

Chisosiamols A–K (1–11), 11 new d-chiro-inositol derivatives, along with a known analogue (12) were isolated from the fruits of Chisocheton siamensis. Their planar structures and relative configurations were elucidated by the comprehensive application of spectroscopic methods, especially from the characteristic coupling constants, and 1H–1H COSY spectra. The absolute configurations of the d-chiro-inositol core were determined using the ECD exciton chirality and X-ray diffraction crystallographic analytical methods. This is the first crystallographic data reported for the d-chiro-inositol derivatives. A structural elucidation strategy mainly combining 1H–1H COSY correlations and ECD exciton chirality for determining the structure of d-chiro-inositol derivatives was developed, which also led to the revisions of previously reported structures. Bioactivity evaluation indicated that chisosiamols A, B, and J can reverse multidrug resistance in MCF-7/DOX cells in the IC50 range of 3.4–6.5 μM (RF: 3.6–7.0).从暹罗洋椿（Chisocheton siamensis）的果实中分离得到11个新的d-手性肌醇（d-chiro-inositol）衍生物奇沙木醇类（Chisosiamols）A–K（1–11），以及1个已知类似物（12）。通过综合运用波谱学方法——尤其是基于特征耦合常数与氢-氢相关谱（1H–1H COSY）谱图数据——阐明了所有化合物的平面结构与相对构型。采用电子圆二色（ECD）激子手性法与X射线衍射晶体分析法，确定了d-手性肌醇母核的绝对构型。本研究首次报道了d-手性肌醇衍生物的晶体学数据。本研究建立了一套主要结合氢-氢相关谱关联与电子圆二色激子手性的d-手性肌醇衍生物结构解析策略，并借此修正了此前已报道的相关化合物结构。生物活性评价结果显示，奇沙木醇类A、B与J可逆转MCF-7/DOX细胞的多药耐药性，其半数抑制浓度（IC50）范围为3.4–6.5 μM，逆转倍数（RF）为3.6–7.0。