Polyols of a cascade type as a water-solubilizing element of carborane derivatives for boron neutron capture therapy
Polyols of a cascade type as a water-solubilizing element of carborane derivatives for boron neutron capture therapy
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作为碳硼烷衍生物的水溶性元素的级联型多元醇用于硼中子俘获疗法
DOI：
10.1021/jo00028a010
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发表时间：
1992
影响因子：
3.6
通讯作者：
Yoshinori Yamamoto
中科院分区：
文献类型：
--
作者：
H. Nemoto;J. G. Wilson;Hiroyuki Nakamura;Yoshinori Yamamoto
开发了一种合成级联型多元醇的实用方法，作为用于硼中子捕获疗法（BNCT）的碳硼烷衍生物的水溶性元素。连接到四醇6a上的碳硼烷以5.44M的浓度溶解在水中。在水性或生物介质中的溶解度差一直是有效地将潜在有用的硼化合物递送至肿瘤部位的障碍。就碳硼烷而言，转化为相应的nido结构，1（可以以钠盐或钾盐形式分离）已用于制备更可溶的衍生物。然而，并不总是能达到令人满意的溶解度水平，并且分子中的其他敏感基团并不总是能在相对严格的反应条件下生存以形成巢结构。此外，尼多化合物在体内的稳定性尚未得到充分记录，并且它们的离子特征表明与反应中心相互作用的可能性很高。另一方面，非极性碳硼烷在很大程度上受到笼的亲脂特性的保护，免受这种相互作用。因此，需要非离子水溶性碳硼烷衍生物，其已引起人们对连接有碳水化合物或其他极性亲水官能团的硼载体的合成的兴趣增加。此类化合物包括羟烷基化碳硼烷* 1s、2 糖基碳硼烷、3 碳硼烷基卟啉 56、4
A practical method for the synthesis of polyols of a cascade type, as a water-solubilizing element of car-borane derivatives for boron neutron capture therapy (BNCT), was developed. The carborane attached to the tetraol 6a was dissolved in water in a concentration of 5.44 M.Poor solubility in aqueous or biological media has been an obstacle to the effective delivery of potentially useful boron compounds to the tumor site. In the case of car-boranes, conversion to the corresponding nido structures, 1 which may be isolated as sodium or potassium salts, has been used to prepare more soluble derivatives. However, a satisfactory level of solubility is not always achieved, and other sensitive groups in the molecule do not always sur-vive the relatively severe reaction conditions for nidostructure formation. Furthermore, the stability of nido compounds in vivo is not well documented, and their ionic character suggests that interaction with reactive centers is highly probable. The nonpolar carboranes, on the other hand, are protected from such interactions to a large extent by the lipophilic character of the cage. There is, therefore, a need for nonionic water-soluble carborane derivatives that has generated increased interest in the synthesis of boron carriers to which carbohydrate or other polar, hydrophilic, functional groups are attached. Such compounds include hydroxyalkylated carborane* 1s, 2 glycosyl carboranes, 3 carboranyl porphyrins 56, 4