Dibenzoate esters of cis‐tetralin‐2,3‐diol as analogs of (–)‐epigallocatechin gallate: synthesis and crystal structure of anticancer drug candidates,Acta Crystallographica Section C

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Dibenzoate esters of cis‐tetralin‐2,3‐diol as analogs of (–)‐epigallocatechin gallate: synthesis and crystal structure of anticancer drug candidates
Acta Crystallographica Section C ( IF 0.7 ) Pub Date : 2020-11-24 , DOI: 10.1107/s2053229620014916
Ryan Noboru Rutherford ₁ , Shinji Ura ₂ , Tak Hang Chan ₃ , Kozo Fukumoto ₂ , Takanori Nishioka ₄ , Andrea Renzetti ₅

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(−)‐Epigallocatechin gallate (EGCG), the main component of green tea extract, displays multiple biological activities. However, it cannot be used as a drug due to its low cellular absorption, instability and metabolic degradation. Therefore, there is a need to provide analogs that can overcome the limitations of EGCG. In this work, six synthetic analogs of EGCG sharing a common tetralindiol dibenzoate core were synthesized and fully characterized by ¹H NMR, ¹³C NMR, HRMS and IR spectroscopies, and X‐ray crystallography. These are (2R,3S)‐1,2,3,4‐tetrahydronaphthalene‐2,3‐diyl bis[3,4,5‐tris(benzyloxy)benzoate], C₆₆H₅₆O₁₀, and the analogous esters bis(3,4,5‐trimethoxybenzoate), C₃₀H₃₂O₁₀, bis(3,4,5‐trifluorobenzoate), C₂₄H₁₄F₆O₄, bis[4‐(benzyloxy)benzoate], C₃₈H₃₂O₆, bis(4‐methoxybenzoate), C₂₆H₂₄O₆, and bis(2,4,6‐trifluorobenzoate), C₂₄H₁₄F₆O₄. Structural analysis revealed that the molecular shapes of these dibenzoate esters of tetralindiol are significantly different from that of previously reported dimandelate esters or monobenzoate esters, as the acid moieties extend far from the bicyclic system without folding back over the tetralin fragment. Compounds with small fluorine substituents take a V‐shape, whereas larger methoxy and benzyloxy groups determine the formation of an L‐shape or a cavity. Intermolecular interactions are dominated by π–π stacking and C—H…π interactions involving the arene rings in the benzoate fragment and the arene ring in the tetrahydronaphthalene moiety. All six crystal structures are determined in centrosymmetric space groups (either P $\overline{1}$ , P2₁/n, C2/c or I2/a).

中文翻译：

顺式四氢萘-2,3-二醇的二苯甲酸酯作为（-）-表没食子儿茶素没食子酸酯的类似物：抗癌药物候选物的合成和晶体结构

(-)-表没食子儿茶素没食子酸酯（EGCG）是绿茶提取物的主要成分，具有多种生物活性。然而，由于其细胞吸收率低、不稳定性和代谢降解，它不能用作药物。因此，需要提供能够克服EGCG局限性的类似物。在这项工作中，合成了 EGCG 的六种合成类似物，它们具有共同的四氢萘二醇二苯甲酸酯核心，并通过¹ H NMR、¹³ C NMR、HRMS 和 IR 光谱以及 X 射线晶体学进行了充分表征。它们是 (2 R ,3 S )-1,2,3,4-四氢萘-2,3-二基双[3,4,5-三(苄氧基)苯甲酸酯]，C ₆₆ H ₅₆ O ₁₀, 以及类似的酯类双(3,4,5-三甲氧基苯甲酸酯), C ₃₀ H ₃₂ O ₁₀ , 双(3,4,5-三氟苯甲酸酯), C ₂₄ H ₁₄ F ₆ O ₄ , 双[4-(苄氧基)苯甲酸酯]、C ₃₈ H ₃₂ O ₆、双(4-甲氧基苯甲酸酯)、C ₂₆ H ₂₄ O ₆和双(2,4,6-三氟苯甲酸酯)、C ₂₄ H ₁₄ F ₆ O ₄. 结构分析表明，这些四氢萘二醇的二苯甲酸酯的分子形状与先前报道的二扁桃酸酯或单苯甲酸酯的分子形状显着不同，因为酸部分远离双环系统延伸而没有折叠在四氢萘片段上。具有小氟取代基的化合物呈 V 形，而较大的甲氧基和苄氧基决定 L 形或空腔的形成。分子间相互作用主要是 π-π 堆积和 C-H…π 相互作用，涉及苯甲酸酯片段中的芳烃环和四氢萘部分中的芳烃环。所有六种晶体结构都在中心对称空间群中确定（P $\上划线{1}$ , P 2 ₁ / n、C 2/ c或I 2/ a )。

更新日期：2020-12-04

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