Chiral induction in quinoline-derived oligoamide foldamers:: Assignment of helical handedness and role of steric effects
Chiral induction in quinoline-derived oligoamide foldamers:: Assignment of helical handedness and role of steric effects
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DOI：
10.1021/ja0527828
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发表时间：
2005-09-21
影响因子：
15
通讯作者：
Huc, I
中科院分区：
文献类型：
--
作者：
Dolain, C;Jiang, H;Huc, I
喹啉类低聚酰胺基团末端的手性基团可在溶液中产生手性螺旋诱导。使用不同的手性基团，可以用核磁共振和圆二色谱测量从9%到83%的非对映异构体过量。尽管这些相对较弱的数值，以及非对映异构体螺旋在溶液中共存和相互转化的事实，末端手性基团所偏爱的右旋或左旋螺旋感觉可以用X射线结晶学明确地确定。手性诱导的指认是以一种独特的方式进行的，利用外消旋体强烈的共晶倾向，并利用缓慢的螺旋转化速度，这使得人们能够建立在晶体中观察到的立体异构体确实与溶液中的主要立体异构体相对应。在立体学的基础上对手性螺旋诱导的意义进行了合理化。用四个取代基按大小递减的命名法将R-S手性或S-S手性指定给立体中心时，观察到Rs手性总是有利于左旋螺旋度，S-S手性有利于右旋螺旋度(P)。X-射线结构揭示了立体化合物在手性诱导机制中的作用。立体中心的首选构象显然是最大的基团应优先指向远离螺旋的位置，第二大基团应与螺旋骨架对齐，最小的基团应指向螺旋。
Chiral groups attached to the end of quinoline-derived oligoamide foldamers give rise to chiral helical induction in solution. Using various chiral groups, diastereomeric excesses ranging from 9% to 83% could be measured by NMR and circular dichroism. Despite these relatively weak values and the fact that diastereomeric helices coexist and interconvert in solution, the right-handed or left-handed helical sense favored by the terminal chiral group could be determined unambiguously using X-ray crystallography. Assignment of chiral induction was performed in an original way using the strong tendency of racemates to cocrystallize, and taking advantage of slow helix inversion rates, which allowed one to establish that the stereomers observed in the crystals do correspond to the major stereomers in solution. The sense of chiral helical induction was rationalized on the basis of sterics. Upon assigning an R-s or S-s chirality to the stereogenic center using a nomenclature where the four substituents are ranked according to decreasing sizes, it is observed that Rs chirality always favors left-handed helicity and S-s chirality favors right-handed helicity (P). X-ray structures shed some light on the role of sterics in the mechanism of chiral induction. The preferred conformation at the stereocenter is apparently one where the bulkiest group should preferentially point away from the helix, the second largest group should be aligned with the helix backbone, and the smallest should point to the helix.