Pressure and temperature-controlled enantiodifferentiating [4+4] photocyclodimerization of 2-anthracenecarboxylate mediated by secondary face- and skeleton-modified gamma-cyclodextrins

A series of secondary-face-substituted and skeleton-modified gamma-cyclodextrins (gamma-CDs) were prepared as chiral hosts for enantiodifferentiating [4+4] photocyclodimerization reactions of 2-anthracenecarboxylic acid (AC). These gamma-CD derivatives form stable ternary complexes with ACs, with altroside-bearing gamma-CDs undergoing induced-fit conformational changes upon complexation, and the photocyclodimerization of AC was, thus, dramatically accelerated. The enantiomeric excess (ee) of anti-head-to-head cyclodimer 3 was greatly enhanced in general with altroside-bearing gamma-CDs 7-9. Although mono-altro-gamma-CD 9 and 3A-azido-3A-deoxy-altro-gamma-CD 7 gave 2 in ee's smaller than those obtained with native gamma-CD, 3A-amino-3A-deoxy-altro-gamma-CD 8 yielded 2 in much higher ee's, which is likely to be ascribed to the combined effects of the less-symmetric cavity and the electrostatic interactions. The influence of temperature and high pressure on the supramolecular photochirogenic reaction has been investigated in depth. An ee as high as 71% was obtained for cyclodimer 2 in the photocyclodimerization of AC mediated by 8 at 210 MPa and -21.5 degrees C.     

Enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid mediated by gamma-cyclodextrins with a flexible or rigid cap

[reaction: see text] A series of modified gamma-cyclodextrins (CDs) with a flexible or rigid cap, synthesized and used as chiral supramolecular hosts for mediating the enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid, significantly improved the chemical and optical yields of chiral head-to-head cyclodimer 3, while the gamma-CD with a rigid cap dramatically inverted the stereochemical outcomes and further improved the enantioselectivities of both head-to-tail and head-to-head dimers 2 and 3.     

A remarkable stereoselectivity switching upon solid-state versus solution-phase enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid mediated by native and 3,6-anhydro-γ-cyclodextrins

The enantiodifferentiating [4+4] photocyclodimerization of anthracenecarboxylic acid (AC) mediated by native, mono- and di-3,6-anhydro-γ-cyclodextrins was investigated in both aqueous solution and solid-state. The solid-state photolyses gave inherently disfavored head-to-head photodimers in much higher chemical and optical yields than in the aqueous solution.     

Template-assisted stereoselective photocyclodimerization of 2-anthracenecarboxylic acid by bispyridinio-appended gamma-cyclodextrin

[reaction: see text] Four kinds of bispyridinio-appended gamma-cyclodextrin (gamma-CD) were prepared to make a molecular flask for controlling the stereoselectivity of photocyclodimerization of 2-anthracenecarboxylate. When the photocyclodimerization of 2-anthracenecarboxylate was carried out in the presence of A,E-bispyridinio-appended gamma-CD, the relative yield of one of the configurational isomers, the head-to-head/anti-isomer, was increased 1.8-fold compared to the corresponding yield in the presence of unmodified gamma-CD or in the absence of any gamma-CD. The optical yields of the photocyclodimerization reaction products also increased more than 10-fold by the addition of bispyridinio-appended gamma-CD compared with unmodified gamma-CD.     

Enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid using a chiral N-(2-hydroxymethyl-4- pyrrolidinyl)benzamide template

[Structure: see text] Supramolecular enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylic acid (AC) was performed in the presence of (2S,4S)-4-amino-5-chloro-2-methoxy-N-(1-ethyl-2-hydroxymethyl-4-pyrrolidinyl)benzamide (TKS159), and its stereoisomers were employed as chiral templates. The TKS template provides us with a novel hydrogen-bonding and shielding motif for enantioface-selectively binding an AC molecule. Chiral products 2 and 3 were obtained in good enantiomeric excesses (ee's) of 40% and 40%, respectively.     

Supramolecular Enantiodifferentiating Photocyclodimerization of 2-Anthracenecarboxylic Acid Mediated by Bridged β-Cyclodextrins: Critical Effects of the Host Structure,pH and Co-Solvents

Several sulfoxide- and sulfone-bridged β-cyclodextrin (CD) dimers were synthesized for mediating the enantiodifferentiating [4+4] photocyclodimerization of 2-anthracenecarboxylic acid (AC). The complexation behavior of these chiral hosts with AC was investigated by UV-vis, circular dichroism, fluorescence, and NMR spectroscopies and certified the formation of 1 : 1 and 1 : 2 host-guest complexes. The product distribution and enantioselectivity of the photoreaction turned out to be a critical function of the chemical structure of bridged CDs. Comparing to the sulfur-bridged 2A_X−3G_X β-CD dimer 7 , the conversion of the photolyzes with sulfoxide-bridged was significantly improved, and the ee of cyclodimer 2 was remarkably increased from −82.8% with 7 to −96.7% with the sulfoxide-bridged 2A_X−3G_X β-CD dimer 8 . The relative yields and ee values of the slipped cyclodimers 5 and 6 were greatly enhanced in the presence of 6 M CsCl. The reaction selectivity is susceptible to the pH variation of the aqueous buffer solution, demonstrating that the supramolecular photochirogenesis is controlled by multidimensional factors, including the chemical structure of the chiral host, solvent, and pH conditions.     

Electrostatic manipulation of enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylate within gamma-cyclodextrin cavity through chemical modification. inverted product distribution and enhanced enantioselectivity

In the enantiodifferentiating supramolecular photocyclodimerization of 2-anthracenecarboxylate using gamma-cyclodextrin with a dicationic side chain, a dramatic switching of the product selectivity and a significant enhancement of the enantiomeric excess were achieved by introducing a flexible dicationic sidearm to native gamma-cyclodextrin and also by lowering the temperature and solvent polarity.     

Highly stereoselective photocyclodimerization of alpha-cyclodextrin-appended anthracene mediated by gamma-cyclodextrin and cucurbit[8]uril: a dramatic steric effect operating outside the binding site

Photocyclodimerization of alpha-cyclodextrin (CD)-appended anthracene was studied in the presence of gamma-CD and cucurbit[8]uril (CB[8]) hosts to manipulate the stereodifferentiating photoreaction occurring inside the cavity by the bulky attachment located outside. The gamma-CD-mediated photodimerization afforded the head-to-tail photodimers in 98% combined yield, in particular, the syn-head-to-tail photodimer of 91% ee in 68% yield, which are much greater than 32% ee and 44% yield obtained with unmodified anthracene carboxylate. The use of CB[8] also led to a striking inversion of the head-to-tail/head-to-head selectivity, affording exclusively the head-to-head photodimers in 99% combined yield.     

Pressure control of enantiodifferentiating photoisomerization of cyclooctenes sensitized by chiral benzenepolycarboxylates. The origin of discontinuous pressure dependence of the optical yield

Pressure effects on enantiodifferentiating geometrical photoisomerizations of (Z)-cyclooctene and (Z,Z)-cycloocta-1,5-diene sensitized by chiral benzene-1,2,4,5-tetracarboxylate were investigated over a pressure range of 0.1-750 MPa. Enantiomeric excesses (ee's) of the (E)- and (E.Z)-isomers obtained displayed discontinuous pressure dependencies, affording distinctly different differential activation volumes (delta delta V++) for each range, indicating alteration of the enantiodifferentiation mechanism. The switching of delta delta V++ occurred at essentially the same pressures of 200 and 400 MPa, which are shared by all the chiral sensitizers, irrespective of the chiral auxiliary employed. Circular dichroism spectral examinations at pressures of up to 400 MPa also revealed that the chiral sensitizers undergo discontinuous conformational changes at 200 MPa, which most likely lead to switching of the enantiodifferentiating sensitization mechanism in the exciplex intermediate.     

天然和修饰环糊精的不对称光化学

用修饰的α-,β-,γ-环糊精(CDs)的包结增感作用研究(Z)-环辛烯(1Z)向手性(E)-异构体(1E)的超分子对映差向光异构反应。建立定量圆二色(CD)和差圆二色(DCD)公式, 研究修饰α-,β-,γ-环糊精衍生物与1Z包结反应的构象、化学量和稳定常数。 实验发现结合诱导的CD光谱变化是温度和修饰环糊精浓度的临界函数。同时发现光稳态E/Z随照射时间增长而增加最后达到光稳定状态, 但明显依赖于增感剂结构和溶液中甲醇含量,它与环糊精手性空腔被客体1Z占有率有直接关系。考查含o-,m-,p-羧酸甲酯基团的苯甲酸β-环糊精酯衍生物的光增感和对映差向能力,更好地认识到在CDs空腔内的有效光能转换是怎样发生的。用邻苯二甲酸β-环糊精酯的对映体过剩（ee）从2.9% 增加到24%。有趣的是产物的ee值与取代基常数（Hammett,σ）间没有明显的关系,却与某些苯甲酸β-CD酯的主体占有率有直接关系,即是通过分析在不同甲醇含量的水溶液中被一些β-CD衍生物增感的对映差向光异构反应中的ee,得出被底物1Z占有主体空腔的百分率 。     

Enantiodifferentiating photoisomerization of (Z,Z)-1,3-cyclooctadiene included and sensitized by naphthoyl-curdlan

6-O-(2-naphthoyl)curdlan was newly synthesized as a sensitizing polysaccharide host to examine the chiroptical properties, supramolecular complexation, and photochirogenic behavior with (Z,Z)-1,3-cyclooctadiene (1ZZ). The enantiodifferentiating photoisomerization of 1ZZ included and sensitized by this polysaccharide host gave a highly strained chiral (E,Z)-isomer in up to 8.7% enantiomeric excess (ee) in solution and 11.7% ee in the solid state, which are the highest values ever reported for a supramolecular photochirogenesis of 1EZ.     

Switched enantioselectivity by solvent components and temperature in photocyclodimerization of 2-anthracenecarboxylate with 6~A,6~X-diguanidio-γ-cyclodextrins

A series of 6A,6X-diguanidio-g-cyclodextrins (CDs) were synthesized as chiral hosts for mediating the enantiodifferentiating[4+4] photocyclodimerization of 2-anthracenecarboxylic acid (AC). Variation of the temperature and the ammonia contents led to greatly enhanced head-to-head photodimers 3 and 4, companying by inversion of product chirality.     

Entropy-controlled supramolecular photochirogenesis: enantiodifferentiating Z-E photoisomerization of cyclooctene included and sensitized by permethylated 6-O-modified beta-cyclodextrins

Permethylated 6-O-modified beta-cyclodextrins 2a-2d were synthesized as novel photosensitizing hosts with a flexible skeleton. Circular dichroism (CD) and 2D NMR spectral examinations of benzoate 2a revealed that the benzoate moiety is deeply included into its own cavity in aqueous solution. Upon addition of (Z)-cyclooctene (1Z) to a 50% aqueous methanol solution of 2a at 25 degrees C, the benzoate moiety of 2a was gradually excluded from the cavity as indicated by the CD spectral changes; the Job's plot revealed the formation of a 1:1 complex of 2a with 1Z. The binding constants for the complexation of 1Z by 2a were determined by CD spectral titration in 50% aqueous methanol at various temperatures. The van't Hoff analysis of the obtained data afforded the thermodynamic parameters (DeltaH degrees = -3.1 kJ mol(-1), DeltaS degrees = 48.5 J mol(-1) K(-1)), demonstrating the entropy-driven complexation by the permethylated cyclodextrin. This is in sharp contrast to the complexation of 1Z by nonmethylated beta-cyclodextrin benzoate that is driven by enthalpy (DeltaH degrees = -31.8 kJ mol(-1) and DeltaS degrees = -51.1 J mol(-1) K(-1)). Upon supramolecular photosensitization with 2a-2d, 1Z isomerized to the (E)-isomer (1E) in moderate enantiomeric excesses (ee's), which however displayed significant temperature dependence with accompanying switching of the product's chirality in an extreme case. Such dynamic behavior of ee is very different from that reported for the photosensitization with nonmethylated cyclodextrin benzoate, where the product's ee is controlled by host occupancy. Eyring treatment of the ee obtained at various temperatures (<0 degrees C) gave the differential activation parameters for the enantiodifferentiation process occurring in the supramolecular exciplex, revealing the crucial role of entropy, as indicated by the DeltaDeltaS(++) value changing dynamically from +4 to -24 J K(-1) mol(-1). The origin of the contrasting behavior of permethylated versus nonmethylated cyclodextrin hosts is inferred to be the conformational flexibility of the former host, which enables the entropy-driven guest complexation in the ground state and the entropy-controlled enantiodifferentiation in the excited state.     

Separation of multicomponent mixtures of 2,4-dinitrophenyl labelled amino acids and their enantiomers by capillary zone electrophoresis

The use of capillary zone electrophoresis (CZE) for the separation of a group of 33 2,4-dinitrophenyl labeled amino acids (DNP-AA), including DNP-AA racemates, DNP-L-AA enantiomers and achiral DNP-AAs, was investigated. Alpha-, beta- and gamma-cyclodextrins (CDs) and their derivatives (hydroxypropyl derivatives of alpha-, beta- and gamma-CDs, polymeric beta-CD and 6A-methylamino-beta-cyclodextrin (MA-beta-CD)) served as complexing agents and chiral selectors in this investigation. Although native alpha- and gamma-CDs and their derivatives influenced the effective mobilities of the studied DNP-AAs in different ways, they generally failed to resolve enantiomers of the individual DNP-AAs. On the other hand, beta-CD and all of its derivatives were found to be effective in this respect. Of these, the best results were achieved with a positively charged MA-beta-CD and this chiral selector resolved enantiomers of ten DNP-AA racemates available for this study. However, a complete resolution of these enantiomers in one CZE run required that the effect of the chiral selector be complemented by complexing effects of polyvinyl pyrrolidone (PVP) or gamma-CD. Complexing and chiral recognition capabilities of MA-beta-CD combined with complexing effects of gamma-CD and PVP provided separating conditions suitable for the CZE separations of multicomponent mixtures of DNP-AAs with preserved resolutions of the enantiomers. For example, a mixture consisting of 43 DNP-AA constituents was resolved using an MA-beta-CD/gamma-CD combination with three peak overlaps.     

Enantiodifferentiating photoisomerization of cyclooctene included and sensitized by aroyl-beta-cyclodextrins: a critical enantioselectivity control by substituents

A series of 6-O-benzoyl-beta-cyclodextrins (CDs) with methyl, methoxy, methoxycarbonyl, and bromo substituent(s) at the ortho-, meta-, and/or para-position(s) were synthesized as chiral sensitizing hosts for the use in supramolecular enantiodifferentiating photoisomerization of (Z)-cyclooctene (1Z) to its chiral (E)-isomer (1E). The complex stability constants (K(S)) of the modified beta-CDs with 1Z in aqueous methanol solutions were highly sensitive to the substituent(s) introduced to the benzoate moiety, and the log K(S) values decreased linearly with slightly different slopes with increasing methanol content. The enantiomeric excess (ee) of 1E obtained upon photosensitization with these hosts was a critical function of the size and position of the substituent, varying from almost zero to 46% ee. This indicates that even an apparently small structural difference between methyl and methoxy can critically affect the enantiodifferentiating photoisomerization of a guest included in the chiral cavity, probably through manipulation of both the orientation of ground-state 1Z and the subsequent rotational relaxation of excited 1Z inside the chiral cavity.     

Excited state enantiodifferentiating interactions between a chiral benzophenone derivative and nucleosides

Time-resolved measurements using nanosecond laser flash photolysis have revealed significant enantiodifferentiation in the interaction between ketoprofen (a chiral benzophenone derivative) and two relevant nucleosides, namely, thymidine and 2'-deoxyguanosine. In both cases, the highest quenching rate constants have been observed for (R)-ketoprofen, the enantiomer with lower pharmacological activity. Photoproduct studies performed in the case of thymidine suggest that the enantiodifferentiating process corresponds to a Paterno-Büchi reaction, leading to the formation of oxetanes. With 2'-deoxyguanosine, the quenching is associated with an electron-transfer process monitored through the generation of a ketyl radical.     

Unusual temperature dependence of enantioselectivity in asymmetric reductions by chiral NADH models

[reaction: see text] Unusual stereoselectivity changes, i.e., enhancement and inversion of enantioselectivity with increasing temperature, were observed in the asymmetric reduction of methyl benzoylformate with chiral 1,4-dihydropyridines possessing amino acid residues as ligating chiral auxiliaries. The differential activation parameters, DeltaDeltaH(S-R) and DeltaDeltaS(S-R), obtained from the Eyring plots demonstrate that the entropy term controls the enantiodifferentiating step, accounting for the observed unique temperature dependencies.     

Bovine serum albumin-mediated enantiodifferentiating photocyclodimerization of 2-anthracenecarboxylate

Enantiodifferentiating photocyclodimerization of 2-anthracenecarboxyalate (AC) was performed at 25 degrees C in aqueous buffer solution (pH 7) in the presence of bovine-serum albumin (BSA) to afford four [4 + 4] cyclodimers, i.e., anti- and syn-head-to-tail (HT) (1 and 2) and anti- and syn-head-to-head (HH) dimers (3 and 4), of which only 2 and 3 are chiral. We found that (1) BSA possesses four sets of binding sites for AC of different affinities, stoichiometries, and chiral environment for photoreaction, which bind 1, 3, 2, and 3 AC molecules with binding constants of 5.3 x 107, 1.3 x 105, 1.4 x 104, and 3.0 x 103 M-1, respectively, (2) the regioselectivity of photodimerization is switched from HT to HH by adding BSA (the HH/HT ratio varies from 0.28 to 4.3), (3) BSA-mediated photodimerization of AC affords optically active products 2 and 3 of up to 29% and 41% ee, respectively. It is emphasized that the selective excitation of bound substrate, utilizing the spectral shift upon complexation with BSA, is not a prerequisite for efficient photochirogenesis using biomolecules.     

Structure and excitation relaxation dynamics of dimethylanthracene dimer in a gamma-cyclodextrin nanocavity in aqueous solution

Dimethylanthracene (DMA), which exhibits almost no self-association in bulk organic solvents, forms a dimer and emits excimer-like fluorescence in a gamma-cyclodextrin nanocavity in a dilute aqueous solution. The 1Bb and 1La electronic transitions of the DMA dimer split by 2230 and 344 cm(-1), respectively, in a fluorescence excitation spectrum obtained with the excimer-like emission. From these energy splits, the structure of dimer in relation to a dielectric constant inside gamma-CD was discussed on the basis of atom-atom Lennard-Jones potential calculations including Coulombic interactions. Excitation relaxations of DMA in the presence of alpha-, beta-, and gamma-CDs in aqueous solutions were investigated by time-resolved fluorescence. The results suggest that both the hydrated and anhydrated species exist in the alpha- and gamma-CD complexes, while only the anhydrated species exists in the beta-CD complex.