Thermodynamic stability of hydrogen-bonded nanostructures: a calorimetric study

The self-assembly of hydrogen-bonded aggregates (rosettes) in solvent mixtures of different polarity has been studied by calorimetry. The C(50) parameter, the concentration when 50 % of the components are incorporated in the assembly, is used to compare assemblies with different stoichiometry. C(50) for the single rosette 1(3).(BuCYA)(3) (1=N,N-di(4-tert-butylphenyl)melamine; BuCYA=n-butylcyanuric acid) in 1,2-dichloroethane is 25 microM, whereas for double rosettes 2 a(3).(BuCYA)(6) and 2 b(3).(BuCYA) (2=calix[4]arene-dimelamine) it is 0.7 and 7.1 microM, respectively. DeltaG degrees, DeltaH degrees, and TDeltaS degrees values indicate that the thermodynamics of double rosettes reflect the independent assembly of two individual single rosette structures or two rosettes reinforced by additional stabilizing interactions. In more polar solvents the stability of double rosettes decreases. From the correlation of DeltaG degrees with solvent polarity it is predicted that it should be possible to assemble double rosettes in methanol or water. The assembly of 2 b(3).(BuCYA)(6) in 100 % MeOH was proven by (1)H NMR and CD spectroscopy.     

Amplification of chirality: the "sergeants and soldiers" principle applied to dynamic hydrogen-bonded assemblies

The amplification of supramolecular chirality has been studied in dynamic chiral hydrogen-bonded assemblies 1(3).(CA)(6) using "Sergeants and Soldiers" experiments. Previously, we have shown that chiral centers present in either the dimelamine component 1 or the cyanurate component CA quantitatively induce one handedness (M or P) in the assembly. This offers the possibility to study the amplification of chirality under two different kinetic regimes. When chiral dimelamines 1 are used, the exchange of chiral components and (M/P)-interconversion, i.e., interconversion between the (M)- and (P)-isomers of assembly 1(3).(CA)(6), take place via identical pathways (condition A). When chiral cyanurates CA are used, the exchange of chiral components occurs much faster than (M/P)-interconversion (condition B). Experimentally, a much stronger chiral amplification is observed under condition B. For example, the observed chiral amplification for a mixture of chiral and achiral components (40:60) is 46% under condition B and 32% under condition A. Kinetic models were developed to fit the experimental data and to simulate chiral amplification in dynamic systems in general. These simulations show that it is theoretically possible that the diastereomeric excess in a dynamic system is more than 99% with less than 1% chiral component present!     

Diastereoselective noncovalent synthesis of hydrogen-bonded double-rosette assemblies

Chiral centers present either in the dimelamine components of calix[4]arene 1 or in the cyanurate components CA quantitatively induce one handedness (P or M) in the corresponding hydrogen-bonded assemblies 1(3).(CA)(6) (de>98 %). The high degree of chiral induction results from the presence of six chiral centers in close proximity (C(alpha)) to the core of the assembly. A much lower level of chiral induction is observed for assemblies with chiral centers that are more remote (C(beta)). All diastereomerically pure assemblies 1(3).(CA)(6) exhibit very high CD activities (deltavarepsilon(max) approximately 100 L mol(-1) cm(-1)), in sharp contrast to the low CD activities (deltavarepsilon(max)相似文献   

Enantioselective noncovalent synthesis of hydrogen-bonded double-rosette assemblies

The noncovalent synthesis of enantiomerically pure hydrogen-bonded assemblies (M)- and (P)-1(3).(CA)(6) is described. These dynamic assemblies are of one single handedness (M or P), but do not contain any chiral components. They are prepared by using the "chiral memory" concept: the induction of supramolecular chirality is achieved through initial assembly with chiral barbiturates, which are subsequently replaced by achiral cyanurates. This exchange process occurs quantitatively and without loss of the M or P handedness of the assemblies. Racemization studies have been used to determine an activation energy for racemization of 105.9+/-6.4 kJ mol(-1) and a half-life time to racemization of 4.5 days in benzene at 18 degrees C. Kinetic studies have provided strong evidence that the rate-determining step in the racemization process is the dissociation of the first dimelamine component 1 from the assembly 1(3).(CA)(6). In addition to this, it was found that the expelled chiral barbiturate (RBAR or SBAR) acts as a catalyst in the racemization process. Blocking the dissociation process of dimelamines 1 from assembly 1(3).(CA)(6) by covalent capture through a ring-closing metathesis (RCM) reaction produces an increase of more than two orders of magnitude in the half-life time to racemization.     

Chiral discrimination of D- and L-amino acids using iodinated tyrosines as chiral references: Effect of iodine substituent

L-Tyrosine and iodinated L-tyrosines, i.e., 3-iodo-L-tyrosine and 3,5-diiodo-L-tyrosine, are successfully used as chiral references for the chiral discrimination of aliphatic, acidic, and aromatic amino acids. Chiral discrimination is achieved by investigating the collision-induced dissociation spectra of the trimeric complex [Cu(II)(ref)(2)(A) - H](+) ion generated by electro spraying the mixture of D- or L-analyte amino acid (A), chiral reference ligand (ref) and M(II)Cl(2) (M = Ni and Cu). The relative abundances of fragment ions resulted by the competitive loss of reference and analyte amino acids are considered for measuring the degree of chiral discrimination by applying the kinetic method. The chiral discrimination ability increases as the number of iodine atom increases on the aromatic ring of the reference and the discrimination is better with Cu when compared with Ni. A large chiral discrimination is obtained for aliphatic and aromatic amino acids using iodinated L-tyrosine as the reference. Computational studies on the different stabilities of the diastereomeric complexes also support the observed differences measured by the kinetic method. The suitability of the method in the measurement of enantiomeric excess over the range of 2% to 100% ee with relative error 0.28% to 1.6% is also demonstrated.     

Stereocontrol in alkyne cyclocarbonylation reactions promoted by a bioxazoline palladium(II) complex

Insertion of 1,2-disubstituted alkynes into [Pd(CH3)(CO)(BIOX)]+[B{3,5-(CF3)2C6H3}4]- (1), where BIOX=(4S,4'S)-(-)-4,4',5,5'-tetrahydro-4,4'-bis(1-methylethyl)-2,2'-bioxazole, leads to the formation of five-membered palladacycles, which, by reaction with carbon monoxide, produce a mixture of two diastereomeric forms of a palladium complex containing an eta3-allylic gamma-lactone ligand. On leaving the mixture in solution, one isomer was converted into the other, reaching a diastereomeric excess of up to 94 %. The steric and electronic factors responsible for the epimerization process were investigated by theoretical methods. Cleavage of the eta3-allyl--palladium bond by nucleophiles allowed highly substituted chiral butenolides to be synthesized in good enantiomeric excess.     

Living and enantiomer-selective polymerization of allene initiated by Ni complex containing chiral phosphine

In the polymerization of chiral allene by using chiral phosphine complex, the polymerization rate of L-1 is approximately 1.9 times that of D-1. This catalyst has enantiomer-selectivity for the polymerization of chiral allene derivative monomer.     

Molecular "chaperones" guide the spontaneous formation of a 15-component hydrogen-bonded assembly

Chaperones are small molecules that assist in the folding of naturally occurring peptides. There are no examples of small molecules acting as chaperones in the self-assembly of synthetic noncovalent assemblies. In this communication we describe an unprecedented example of the "chaperone effect" in the noncovalent synthesis of organic nanostructures. Tetrarosette assemblies 2(3).(BuCYA)(12) form quantitatively in CHCl(3) at room temperature upon mixing tetramelamine 2 with N-butylcyanurate (BuCYA) in the presence of 5,5-diethylbarbituric acid (DEB). Without the DEB units present, only oligomeric assemblies are formed that cannot rearrange to the tetrarosettes by themselves. The DEB units act as molecular "chaperones" by preorganizing the tetramelamine units for the spontaneous assembly of the tetrarosette structure.     

Optically active perfluoro-2-propoxypropionic acid: A new chiral reagent for 19F NMR study

Perfluoro-2-propoxypropionic acid, which was prepared by the anionic dimerization of hexafluoro-1,2-epoxypropane, was optically resolved via diastereomeric salt formation with chiral amines. The optically pure (+) and (?) perfluoro-2-propoxypropionic acids thus obtained were found to be a convenient chiral reagent for determining enantiomeric compositions of α-amino acids by means of ¹⁹F nmr analysis.     

Structure, reactivity and solution behaviour of [Re(ser)(7-MeG)(CO)(3)] and [Re(ser)(3-pic)(CO)(3)]: "nucleoside-mimicking" complexes based on the fac-[Re(CO)(3)](+) moiety

The fac-[Re(CO)(3)](+) moiety was reacted with the amino acid serine (D- and L-ser) and with 7-methylguanine (7-MeG), 3-methylpyridine (3-pic) or adenine (ade) to yield novel complexes intended as nucleoside-mimicking compounds. Reaction of [Re(H(2)O)(3)(CO)(3)](+)(1) with L-ser yields the complex [Re(L-ser)(2)(CO)(3)](L-2). X-Ray structure analysis of L-2 reveals that one of the two amino acids is bound to the metal centre in a bidentate fashion while the other amino acid is bound as a zwitterion via the carboxylate oxygen only. Reaction of L-2 and of [Re(D-ser)(2)(CO)(3)](D-2) with 7-MeG yields complexes [Re(L-ser)(7-MeG)(CO)(3)](L-3) and [Re(D-ser)(7-MeG)(CO)(3)](D-3) respectively. Complexes L-3 and D-3 are received as a mixture of diastereomers. If 3-pic is used instead of 7-MeG complex [Re(L-ser)(3-pic)(CO)(3)](L-4) is obtained in good yield, while interaction of L-2 with ade gives a mixture of five distinct species. Crystallization gave one single diastereomer for L-3 and D-3 and the two forms for 4 respectively. X-Ray structure analyses reveal that in all cases the amino acid is bound in a chelate fashion with the base occupying the sixth co-ordination site. When crystals of either 2 or 3 are dissolved in a CD(3)OD/D(2)O mixture (1:1, 293 K) rapid transformation to the diastereomeric mixture is observed. While for L-2 this reorganisation is fast on the NMR time scale even at 193 K, the rate constant for the rearrangement of L-3 and D-3 is 1.36 +/- 0.24 x 10(-2) s(-1) at 293 K.     

Synthesis of carbosilane dendritic wedges and their use for the construction of dendritic receptors

A divergent route for the synthesis of carbosilane wedges that contain either a bromine or amine as focal point has been developed. These new building blocks enable the construction of various core-functionalized carbosilane dendrimers. As a typical example carbosilane dendrimers up to the third generation containing a N,N',N'-1,3,5-benzenetricarboxamide core (G1-G3) have been synthesized. This new class of molecules has been studied as host molecules and they have been found to bind protected amino acids as guest molecules via hydrogen bonding interactions. A decrease in the association constants was observed for the higher generation dendritic hosts, which is attributed to the increased steric hindrance around the core where the binding site is located. The binding properties of the dendritic host molecules can be tuned by modifying the binding motif at the core of the carbosilane dendrimers. A higher association constant for N-CBZ-protected glutamic acid 1-methyl ester (5) was observed when the third generation N,N',N'-1,3,5-tris(L-alaninyl)benzenetricarboxamide core-functionalized carbosilane dendrimer (G3') was used as the host molecule compared to G3. Different association constants for the formation of the diastereomeric G3'.L-5(K=295 M(-1)) and G3'.(D-5)(2) (K=236 M(-1)) host-guest complexes were observed, pointing to a small enantioselective recognition effect. The difference between the association constants for the formation of the G3'.(L-5)(2) and G3'.(D-5)(2) host-guest complexes was much more pronounced, K=37 M(-1)versus K=10 M(-1), respectively.     

Enhanced stereoselectivity in photoelectrocyclization of tropolone ethers via confinement in chiral inductor-modified lyotropic liquid crystals

Photochemistry of tropolone methyl ether ( 1) and optically pure ( S)-tropolone-2-methylbutyl ether ( 4) has been examined in lyotropic liquid crystals (LCs) in the presence of a chiral inductor. LCs significantly enhance the influence of chiral inductors during the photoelectrocyclization of the tropolone ethers. Chiral inductors that lead to 1:1 mixtures of enantiomers or diastereomers in solution give products in up to 40% enantiomeric excess for 1 and 35% diastereomeric excess for 4 in LCs.     

Diels-alder reactions with cyclic sulfones: VIII. Organic catalysis in the synthesis of spiro[1-benzothiophene-4,5′-pyrimidine]-2′,4′,6′-trione 1,1-dioxides and 2′-thioxospiro[1-benzothiophene-4,5′-pyrimidine]-4′,6′-dione 1,1-dioxides

5-Isopropenyl-2,3-dihydrothiophene 1,1-dioxide reacted with 5-methylidenepyrimidine-2,4,6-triones and 5-methylidene-2-thioxopyrimidine-4,6-diones in the presence of chiral amines or amino acids with high regio- and stereoselectivity to give optically active derivatives of barbituric and thiobarbituric acids spirofused at the 5-position to 1-benzothiophene 1,1-dioxide fragment. The reaction of 5-isopropenyl-2,3-dihydrothiophene 1,1-dioxide with 5-(2-methoxybenzylidene)-2-thioxopyrimidine-4,6-dione (generated in situ from 2-methoxybenzaldehyde and thiobarbituric acid) in the presence of (?)-ephedrine or L-4-(tert-butyldimethylsiloxy) proline gave the corresponding 2-thioxospiro[1-benzothiophene-4,5′-pyrimidine]-4′,6′-dione 1,1-dioxide with an enantiomeric excess of 80%.     

Synthesis of 4,6-dideoxyfuranoses through the regioselective and diastereoselective oxyfunctionalization of a dimethylphenylsilyl-substituted chiral homoallylic alcohol.

The 4,6-dideoxyfuranoses 10a and 10b have been synthesized by starting from the readily available E-5-dimethylphenylsilyl-2-hexene-4-ol (1) and employing successively three versatile oxyfunctionalization methods, namely photooxygenation, metal-catalyzed epoxidation, and oxidative desilylation. Photooxygenation of the hydroxy vinylsilane 1 and subsequent triphenylphosphine reduction of the hydroperoxides 3 afford the like-4a and unlike-4b diols, which have been converted separately to the tetrahydrofurans (2S*,3R*,5R*)-7a and (2S*,3R*,5S*)-7b by a combination of diastereoselective epoxidation and regioselective intramolecular epoxide-ring opening. In the epoxidation reaction, catalyzed by Ti(OiPr)(4) or VO(acac)(2), only one diastereomer (dr >95:5) of the epoxide 5 is obtained. Further intramolecular opening of the epoxide ring in erythro-5 occurs regioselectively at the C-alpha position and diastereoselectively under inversion of the configuration of the silyl-substituted stereogenic center to generate only one diastereomer of the tetrasubstituted tetrahydrofurans 7. Oxidative desilylation of the latter gave the hitherto unknown 4,6-dideoxyfuranoses 10a and 10b. The use of the optically active E-5-dimethylphenylsilyl-2-hexene-4-ol (1) as starting material, which is readily available through lipase-catalyzed kinetic resolution, leads to the D- and L-4,6-dideoxysorbofuranoses 10a and D- and L-4,6-dideoxyfructofuranoses 10b in up to 98% enantiomeric excess.     

Enantiospecific synthesis of vicinal stereogenic tertiary and quaternary centers by combination of configurationally-trapped radical pairs in crystalline solids

[reaction: see text] Photochemical irradiation of crystalline (2R,4S)-2-carbomethoxy-4-cyano-2,4-diphenyl-3-butanone 1 led to highly efficient decarbonylation reactions. Experiments with optically pure and racemic crystals showed that the intermediate radical pairs undergo a highly diastereo- and enantiospecific radical-radical combination that leads to the formation of two adjacent stereogenic centers in good chemical yield and with high chemical control. Reactions with chiral crystals occurred with quantitative enantiomeric yields and >95% diastereomeric yields.     

Bis(N‐Confused Porphyrin) as a Semirigid Receptor with a Chirality Memory: A Two‐Way Host Enantiomerization through Point‐to‐Axial Chirality Transfer

The adduct formation of protonated bis(N‐confused porphyrin) (BNCP, 3,3′‐bis(meso‐tetratolyl‐2‐aza‐21‐carbaporphyrin) with chiral anions, carboxylic acids, and alcohols was studied in solution by means of ¹H NMR and circular dichroism (CD) spectroscopic analysis and DFT methods. The addition of enantiopure guests to the acidified BNCP resulted in optical activity that vanished after neutralization. Pairs of the ¹H NMR‐distinguishable diastereomers were formed when enantiopure guests were applied, although a single form was observed upon the addition of the racemic mixtures in each case. Unidirectional configuration change that led to diastereomeric excess was observed in several instances. Such an excess was memorized by metalation of the adducts with AgBF₄, thus resulting in optically active silver(III) complexes of BNCP with some enantiomeric excess. Absolute configurations of BNCP cations and bis(zinc) and bis(silver(III)) complexes were determined on the basis of time‐dependent (TD)‐DFT calculations of their CD spectra. It was shown that some of the chiral carboxylates induced opposite directions of enantiomerization of di‐ and tetracations or di‐/tetracation and bis(zinc) complexes. The source of the optical activity of the equimolar diastereomeric mixture of adducts is discussed.     

高效液相色谱法测定非天然氨基酸的光学纯度

 以（1- 氟-2,4-二硝基苯基）-5-L-缬氨 酰胺为手性试剂、反相高效液相色谱法测定非天然氨基酸的光学 纯度。梯度洗脱,流动相A：含体积分数为0.1％的三氟乙酸的乙腈,流动相B：体积分 数为0.1％的三氟乙酸水溶液。L-和D-对映体得到良好分离。准确测定了25种非天然 氨基酸L-和D-对映体的光学纯度。     

Straightforward and Facile Synthesis of a Bioactive Component from Zingiber cassumunar Roxb.

Straightforward and facile synthesis of a bioactive component A from Zingiber cassumunarRoxb. is described. The phenylbutenoid dimer A was reported to possess anti-inflammatory and cytotoxic activities. The optically active cyclohexene ring fragment was obtained via the highly diastereo- and enantioselective Diels–Alder reaction of chiral acryloyloxazolidinones (1a and 1b) and 1-(4-hydroxy-3-methoxyphenyl)butadiene (2). The enantiomeric excess of Diels–Alder adducts 3a and 3bwere determined via high-performance liquid chromatotography of the corresponding bis-acetate (6). The greatest enantiomeric excess (99.9% ee) was obtained when the 4-phenyloxazolidin-2-one (1a) chiral auxiliary was used in combination with TiCl4. The optically pure bioactive compound A was prepared from the optically active Diels–Alder adduct (3a) in two additional steps.     

Chirality transfer from guanidinium ylides to 3-alkenyl (or 3-alkynyl) aziridine-2-carboxylates and application to the syntheses of (2R,3S)-3-hydroxyleucinate and D-erythro-sphingosine

[Reaction: see text]. Reaction of chiral guanidinium ylides with alpha,beta-unsaturated aldehydes gives 3-(alpha,beta-unsaturated) aziridine-2-carboxylates in high diastereo- and enantioselectivities (up to 93% diastereomeric excess and 98% enantiomeric excess). 3-(1-methylvinyl)- and 3-[(E)-pentadec-1-enyl]aziridine-2-carboxylates were successfully employed to prepare (2R,3S)-3-hydroxyleucinate and d-erythro-sphingosine, respectively.     

Complexation of phenolic guests by endo- and exo-hydrogen-bonded receptors

This article describes the complexation of phenol derivatives by hydrogen-bonded receptors. These phenol receptors are formed by self-assembly of calix[4]arene dimelamine or tetramelamine derivatives with 5,5-diethylbarbiturate (DEB) or cyanurate derivatives (CYA). The double rosette assemblies 3(3).(DEB)6/(CYA)6 have their phenol-binding functionalities (ureido groups) at the top and at the bottom of the double rosette (exo-receptors). The tetrarosette assemblies 4(3).(DEB)12/(CYA)12 form a cavity with binding sites between the two double rosettes for guest encapsulation (endo-receptors). An intrinsic binding constant Ka of 202 M-1 and 286 M-1 for the binding of 4-nitrophenol to the ureido functionalized exo- and endo-receptors, respectively, was observed. For the exo-receptor a 1:6 stoichiometry was observed while for the endo-receptor 1:4 binding stoichiometry was determined by Job plot and MALDI-TOF MS. The important role that the hydroxy group's acidity plays in the complexation of 4-nitrophenol is clarified by binding studies with different phenol derivatives. The hydrogen-bonded receptors showed a much smaller response towards less acidic phenol derivatives.