顺铂，卡铂和奥沙利铂的Bispidin-9,9-diol类似物：合成，结构和细胞毒性,Inorganic Chemistry

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顺铂，卡铂和奥沙利铂的Bispidin-9,9-diol类似物：合成，结构和细胞毒性
Inorganic Chemistry ( IF 4.3 ) Pub Date : 2016-02-26 00:00:00 , DOI: 10.1021/acs.inorgchem.5b02855
Huiling Cui ₁ , Richard Goddard ₁ , Klaus-Richard Pörschke ₁ , Alexandra Hamacher ₂ , Matthias U. Kassack ₂

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3,7-二烯丙基-双嘧啶-9-一（6）（bispidin-9-one = 3,7-二氮杂双环[3.3.1] nonan-9-one）被转化为N-未取代的螺环[bispidin-9,2 ′-[1，3]二氧戊环]（12； 35％）。缩酮以无水12a和二水合物12b的形式结晶。无水12a中的分子相互连接，形成具有手性交替的N1-H1···N2-H2···N1 *氢键手性螺旋。在二水合物12b中，缩酮分子通过O3-H··O1和O4-H···N1氢键连接到水分子的中心串，但不相互连接。的反应12用（1,5-己二烯）氯铂酸₂得到几乎定量的螺[bispidin-9,2'-[1,3]二氧戊环] PtCl ₂（13）。裂解缩酮以回收酮产生双生二醇（bispidin-9,9-diol）PtCl ₂（14 ; 85％）。化合物14与Ag ₂ cbdca（cbdca = 1,1-环丁烷二羧酸酯）反应生成二水合物（bispidin-9,9-diol）Pt（cbdca）·2H ₂ O（15b），可以将其脱水以获得无水（bispidin） -9,9-二醇）Pt（cbdca）（15a）。类似地，获得无水（双嘧啶-9，9-二醇）Pt（草酸酯）（16）。14和15b的晶体结构通过各种形式的OH-··O，OH···Cl，NH···Cl和NH···O氢键揭示缔合。生物学研究表明bispidin -9,9-二醇复合物的温和的细胞毒性活性14 - 16，相对于9,9-未取代的bispidine络合物。没有非特异性的细胞毒性14 - 16高达316μM发现对非癌性细胞系HEK293。

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Bispidin-9,9-diol Analogues of Cisplatin, Carboplatin, and Oxaliplatin: Synthesis, Structures, and Cytotoxicity

3,7-Diallyl-bispidin-9-one (6) (bispidin-9-one = 3,7-diazabicyclo[3.3.1]nonan-9-one) is converted to N-unsubstituted spiro[bispidin-9,2′-[1,3]dioxolane] (12; 35%). The ketal crystallizes in the forms of anhydrous 12a and the dihydrate 12b. The molecules in anhydrous 12a are linked to each other, forming N1–H1···N2–H2···N1* hydrogen-bond chiral helices of alternating chirality. In the dihydrate 12b, the ketal molecules are connected to a central string of water molecules by O3–H···O1 and O4–H···N1 hydrogen bonds, but not to themselves. Reaction of 12 with (1,5-hexadiene)PtCl₂ affords almost quantitatively spiro[bispidin-9,2′-[1,3]dioxolane]PtCl₂ (13). Cleavage of the ketal to retrieve the ketone produces the geminal diol (bispidin-9,9-diol)PtCl₂ (14; 85%). Compound 14 reacts with Ag₂cbdca (cbdca = 1,1-cyclobutanedicarboxylate) to give the dihydrate (bispidin-9,9-diol)Pt(cbdca)·2H₂O (15b), which can be dehydrated to obtain anhydrous (bispidin-9,9-diol)Pt(cbdca) (15a). Similarly, anhydrous (bispidin-9,9-diol)Pt(oxalate) (16) is obtained. Crystal structures of 14 and 15b reveal association by various forms of O–H···O, O–H···Cl, N–H···Cl, and N–H···O hydrogen bonds. Biological studies showed a moderate cytotoxic activity of the bispidin-9,9-diol complexes 14–16, compared to the 9,9-unsubstituted bispidine complexes. No unspecific cytotoxicity of 14–16 up to 316 μM was found against the noncancer cell line HEK293.

更新日期：2016-02-26

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