Studies of Synthetic Catechin Analogues Useful for Antioxidant Therapy

“抗氧化物对自由相关疾病的保护作用已经被广泛地研究过，这也提出了新类型的抗氧化物的发展。”一个行星catechin模拟（1H_2），在哪些catechin和chroman moietin被约束为行星，通过Oxa-Pictet Spengler反应使用catechin和丙酮与BF_3.Et_2O进行合成。1H_2利用galvinoxyl（G^·）、稳定的氧中心的基础清除活动进行了测试，显示了从1H_2到G^的氢转移反应是5-比从本地catechin到G^的氢转移更快。从儿茶素到钙钛矿的氢转移的动力学也在丙酸腈（EtCN）中进行了研究，使用ESR时温度较低，显示从P1H_2的氢转移的速率明显高于儿茶素的速率。在基本条件下，1H_2将分子氧化物减少到生产超氧化物阴离子（O_2^<·->）的二氧化物（1^<2->）。However，电子转移率比catechin的速度要慢，建议1H_2可以是一种新型抗氧化剂的承诺，用减少的前氧化剂活性。1H_2还显示了一种在没有前氧化剂效应的情况下对氧化DNA损伤的增强保护效应，在本机催化剂的情况下通常是被观察到的。最后，行星催化剂模拟显示了对O_2产生的较强的激进清除能力和减少的保证效应对O_2^<->。“DNA链筛选的全面抑制也可能导致生物聚合物因反应性氧化物物种而导致的有效保护，从而导致氧化损伤。”1H_2的脂质特性也是用来抑制自由基相关事件的，特别是在细胞膜中。因此， 1H_2可能对自由基相关疾病的预防和/或治疗有很大的影响。

The protective role of antioxidants against free-radical associated diseases has been widely studied and this has prompted the development of new types of antioxidants. A planar catechin analogue (1H_2), in which catechol and chroman moieties in catechin were constrained to be planar, was synthesized via oxa-Pictet Spengler reaction using catechin and aceton with BF_3.Et_2O. The radical-scavenging activities of 1H_2 were examined using galvinoxyl radical (G^・), a stable oxygen-centered radical, showing that the hydrogen transfer reaction from 1H_2 to G^・ is 5-fold faster than that of hydrogen transfer from the native catechin to G^・. The kinetics of hydrogen transfer from catechins to cumylperoxyl radical was also examined in propionitrile (EtCN) at low temperature with use of ESR, showing that the rate of hydrogen transfer from P1H_2 is significantly faster than that from catechin. Under basic conditions, the dianion (1^<2->) of 1H_2 reduced molecular oxygen to produce superoxide anion (O_2^<・->). However, the electron transfer rate was slower than that of catechin, suggesting that 1H_2 may be a promising novel antioxidant with reduced pro-oxidant activity. The 1H_2 also showed an enhanced protective effect against the oxidative DNA damage induced by Fenton reaction without the pro-oxidant effect, which is usually observed in the case of the native catechin.Finally, the planar catechin acalogue showed the strong radical scavenging ability and reduced prooxidant effect responsible for the less-efficient generation of O_2^<・->. The completed inhibition of DNA strand scission is also expected the efficient protection toward oxidative damage of biopolymers caused by the reactive oxygen species. The lipophilic property of 1H_2 is also useful for suppressing free-radical associated event, especially in the cell membrane. Therefore, 1H_2 might be very effective for the prevention and/or treatment of free radical-associated diseases.