Polyene substrates with unusual methylation patterns to probe the active sites of three catalytic antibodies
Polyene substrates with unusual methylation patterns to probe the active sites of three catalytic antibodies
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DOI：
10.1016/s0968-0896(01)00402-3
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发表时间：
2002-05-01
影响因子：
3.5
通讯作者：
Janda, KD
中科院分区：
文献类型：
--
作者：
Kim, GT;Wenz, M;Janda, KD
合成两种四烯，其甲基化模式与羊毛甾醇生物合成中的天然底物2，3-氧化角鲨烯不同。并描述了用三种催化抗体对其进行的检测。这些新的线性萜类化合物结构的设计由三种催化抗体的表征获得的初步结果决定。这些是通过用类固醇半抗原免疫产生的，所述类固醇半抗原模拟多环化而不需要抗马可夫尼科夫加成或环扩增。与羊毛甾醇、环阿屯醇和β-香树脂素生物合成中观察到的氧化角鲨烯环化相比，这种反应级联将代表更“原始”的版本，并且不需要如角鲨烯中所见的第三和第四异戊二烯单元的尾对尾连接。第一个四烯设计（A）仅含有三取代的双键，因此其合成从法尼醇和三-降香叶醇开始。第二个四烯设计（B）被认为与诱导半抗原更精确地匹配，所述诱导半抗原通过显示一个二取代的双键产生抗体集合，并且其合成利用三香叶醇衍生物和对称的双烯丙醇作为关键结构单元。色谱比较研究得出的结论是，目前研究的抗体也从两种底物产生单环产物，如以前用角鲨烯衍生底物观察到的。相反，2，3-氧化角鲨烯不被这些催化剂接受，这支持了当前底物通过识别两个末端官能团而完全结合的观点。(C)2002爱思唯尔科技有限公司。保留所有权利。
The synthesis of two tetraenes that differ in their methylation pattern from the natural substrate in lanosterol biosynthesis, 2,3-oxidosqualene. and their examination with three catalytic antibodies is described. The design of these novel, linear terpenoid structures was governed by initial results obtained from the characterization of the three catalytic antibodies. These were generated by immunization with a steroidal hapten that mimics multicyclization without the necessity for anti-Markovnikov additions or ring expansions. Such a reaction cascade would represent a more 'primitive' version compared to the oxidosqualene cyclization observed in lanosterol, cycloartenol and P-amyrin biosynthesis and would not require a tail-to-tail connection of the third and fourth isoprene unit as seen in squalene. The first tetraene design (A) only contains trisubstituted double bonds and hence its synthesis starts from farnesol and tris-norgeraniol. The second tetraene design (B) is considered the more precise match to the inducing hapten that generated the antibody collections by exhibiting one disubstituted double bond and its synthesis utilizes a trisnorgeraniol derivative and a symmetrical bis-allylic alcohol as key building blocks. Chromatographic comparison studies lead to the conclusion that the currently studied antibodies also produce monocyclic products from the two substrates as has been formerly observed with a squalene-derived substrate. In contrast, 2,3-oxidosqualene is not accepted by these catalysts supporting the notion that the current substrates are fully bound by recognition of both terminal functional groups. (C) 2002 Elsevier Science Ltd. All rights reserved.