Molecular Clefts Derived from 9,9′‐spirobi[9H‐fluorene] for enantioselective complexation of pyranosides and dicarboxylic acids
Molecular Clefts Derived from 9,9′‐spirobi[9H‐fluorene] for enantioselective complexation of pyranosides and dicarboxylic acids
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9,9-螺二[9H-芴]衍生的分子裂缝用于吡喃苷和二羧酸的对映选择性络合
DOI：
10.1002/hlca.19950780209
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发表时间：
1995
影响因子：
1.8
通讯作者：
F. Diederich
中科院分区：
文献类型：
--
作者：
J. Cuntze;L. Owens;Victoria Alcázar;P. Seiler;F. Diederich
通过（R）-和（S）-9，9 ′-螺[9 H-芴]-2，2 ′-二羧酸（5）的双（琥珀酰亚胺-N-基酯），合成了以9，9 ′-螺[9 H-芴]为间隔基，以两个N-（5，7-二甲基-1，8-萘啶-2-基）甲酰胺（CONH（naphthy））为氢键的分子裂缝（R）-和（S）-3。具有一个CONH（萘基）单元和一个琥珀酰亚胺-N-基酯残基的衍生物6允许容易地接近具有两个不同H-键合位点的螺二芴裂缝，如4的合成所例示的。在CDCl 3中，（R）-和（S）-3与光学活性二羧酸的结合研究显示，所形成的非对映异构体复合物的自由能（Δ（ΔGo））差异在0.5和1.6 kcal mol−1（T 300 K）之间。用带有两个N-（6-甲基吡啶-2-基）甲酰胺（CONH（py））H-键合位点的螺二芴裂缝（R）-和（S）-1观察到类似的对映选择性。通过变温1H-NMR滴定法测定了（R）-和（S）-1识别过程的热力学量ΔHo和ΔSo，并与（R）-和（S）-2识别过程的热力学量进行了比较，（R）-和（S）-2具有两个CONH（py）部分连接在构象更灵活的1，1 ′-联萘裂缝的6，6 ′-位上。所有的关联过程都表现出高的熵驱动力，这部分是由熵的不利变化补偿。吡喃糖苷与CDCl 3中的光学活性断裂1和3结合，−ΔGo = 3.0-4.3 kcal mol−1。观察到非对映异构体选择性高达1.2 kcal mol−1，对映体选择性高达0.4 kcal mol−1。裂解物4和N-（5，7-二甲基-1，8-萘啶-2-基）乙酰胺（25）与吡喃糖苷22-24的络合效果与3相同，表明3中只有一个CONH（萘基）位点与糖衍生物强烈缔合。根据3的X-射线晶体结构，建立了（S）-3与吡喃糖苷22配合物的计算机模型。分子动力学（MD）模拟表明微分几何约束是二元羧酸（S）-7与（R）-和（S）-1和（R）-和（S）-3络合的高对映选择性的起源。
The molecular clefts (R)- and (S)-3, incorporating 9,9′-spirobi[9H-fluorene] as a spacer and two N-(5,7-dimethyl-1,8-naphthyridin-2-yl)carboxamide (CONH(naphthy)) units as H-bonding sites were prepared via the bis(succinimid-N-yl esters) of (R)-and (S)-9,9′-spirobi[9H-fluorene]-2,2′-dicarboxylic acid (5). Derivative 6, with one CONH(naphthy) unit and one succinimid-N-yl ester residue allowed easy access to spirobifluorene clefts with two different H-bonding sites, as exemplified by the synthesis of 4. Binding studies with (R)- and (S)-3 and optically active dicarboxylic acids in CDCl3 exhibited differences in free energy of the formed diastereoisomeric complexes (Δ(ΔGo)) between 0.5 and 1.6 kcal mol−1 (T 300 K). Similar enantioselectivities were observed with the spirobifluorene clefts (R)- and (S)-1, bearing two N-(6-methylpyridin-2-yl)carboxamide (CONH(py)) H-bonding sites. The thermodynamic quantities ΔHo and ΔSo for the recognition processes with (R)- and (S)-1 were determined by variable-temperature 1H-NMR titrations and compared to those with (R)- and (S)-2, which have two CONH(py) moieties attached to the 6,6′-positions of a conformationally more flexible 1,1′-binaphthyl cleft. All association processes showed high enthalpic driving forces which are partially compensated by unfavorable changes in entropy. Pyranosides bind to the optically active clefts 1 and 3 in CDCl3 with −ΔGo = 3.0–4.3 kcal mol−1. Diastereoisomeric selectivities up to 1.2 kcal mol−1 and enantioselectivities up to 0.4 kcal mol−1 were observed. Cleft 4 and N-(5,7-dimethyl-1,8-naphthyridin-2-yl)acetamide (25) complexed pyranosides 22–24 as effectively as 3 indicating that only one CONH(naphthy) site in 3 associates strongly with the sugar derivatives. Based on the X-ray crystal structure of 3, a computer model for the complex between (S)-3 and pyranoside 22 was constructed. Molecular-dynamics (MD) simulations showed that differential geometrical constraints are at the origin of the high enantioselectivity in the complexation of dicarboxylic acid (S)-7 by (R)- and (S)-1 and (R)- and (S)-3.