An inherently chiral calix[4]crown carboxylic acid in the partial cone conformation

We have designed and synthesized an inherently chiral calix[4]arene partial cone conformer, in which a crown-4 ether moiety, a carboxyl group, and a propyl group are convergent. Chemical resolution was achieved by use of (S)-BINOL as a chiral auxiliary. ¹H NMR titration data revealed that the title compound does not have the ability to differentiate both enantiomers of chiral amine and aminoalcohol guests. The approximately symmetric calix[4]arene skeleton of the partial cone conformer is presumed to be responsible for its undesirable chiral recognition ability.     

Synthesis of novel chiral Schiff base and amino alcohol derivatives of calix[4]arene and chiral recognition properties

In the present study, the synthesis and liquid phase extraction properties towards some amino acid methylesters and amino alcohols of Schiff base and amino alcohol substituted calix[4]arene are reported. The Schiff base substituted calix[4]arene 5 has been synthesized via condensation reaction involving 5,17-diformyl-11,23-di-tert-butyl-25,27-di[3-(4-formylphenoxy)propoxy]-26,28 dihydroxycalix[4]arene 4 and (R)-(?)-2-phenylglycine methyl ester in CHCl₃:MeOH. To give the amino alcohol substituted calix[4]arene 6, the synthesized chiral compound 5 was reduced by LiAlH₄. The new chiral Schiff base and amino alcohol derivatives of calix[4]arene have been characterized by a combination of FT-IR, ¹H NMR, ¹³C NMR, FAB-MS and elemental analysis. Also, the extraction behaviors of 5 and 6 towards some selected amino acid methylesters and amino alcohols have been studied by liquid–liquid extraction.     

One-step synthesis of inherently chiral p-tert-butylcalix[4]azacrown

A one-step procedure is developed to synthesize inherently chiral p-tert-butylcalix[4]azacrown 1 through etherification between p-tert-butylcalix[4]arene and compound 3, which can be amplified to efficiently prepare more inherently chiral calix[4]arenes in ABHH substitution pattern.     

Preparation and evaluation of calix[4]arene-capped beta-cyclodextrin-bonded silica particles as chiral stationary phase for high-performance liquid chromatography

Calix[4]arene-capped [3-(2-O-beta-cyclodextrin)-2-hydroxypropoxy]propylsilyl-appended silica particles (C4CD-HPS), a new type of substituted beta-cyclodextrin-bonded chiral stationary phase (CSP) for high-performance liquid chromatography (HPLC), have been synthesized by treatment of bromoacetate-substituted [3-(2-O-beta-cyclodextrin)-2-hydroxypropoxy]propylsilyl-appended silica particles (BACD-HPS) with calix[4]arene oxyanions in anhydrous N-methyl-2-pyrrolidone. The synthetic stationary phase is characterized by means of elemental analysis. This new type of CSP has a chiral selector with two recognition sites: calix[4]arene and beta-cyclodextrin (beta-CD). The chromatographic behavior of C4CD-HPS was studied with several disubstituted benzenes and some chiral drug compounds under reversed-phase conditions. The results show that C4CD-HPS has excellent selectivity for the separation of aromatic positional isomers and enantiomers of chiral compounds due to the cooperative functioning of calix[4]arenes and beta-CDs.     

Inherently chiral biscalixarene cone–cone conformers consisting of calix[4]arene and calix[5]arene subunits

Inherently chiral biscalixarenes with hetero-cavities were synthesized by a covalent assembly of p-tert-butylcalix[5]arene with a 1,3-substituted calix[4]arene via 1,3-alkylation reaction and subsequent desymmetrization. The racemates were resolved by chiral HPLC method. ¹H NMR spectra, VT-NMR spectra, and theoretical calculations support that the calix[5]arene subunit of the inherently chiral calix[4][5]arene ester adopts a cone-in conformation, with the aromatic ring bearing the CH₂CO₂Et group tilting inward the calix[5]arene cavity. By contrast, such a cone-in structural feature of the calix[5]arene subunit disappears for the corresponding inherently chiral calix[4][5]arene carboxylic acid, due to the intramolecular hydrogen bonding between the carboxyl group and an ethereal oxygen of the glycolic chain.     

Preparation of enantiopure inherently chiral calix[5]arenes

Enantiopure inherently chiral calix[5]arenes were successfully prepared by separation of their (R)-BINOL diastereomeric derivatives of the corresponding racemates by column chromatography instead of HPLC. A new type of inherently chiral calix[5]arene was obtained.     

Synthesis of chiral calix[4]arenes bearing tartaric ester moieties

The synthesis of chiral calix[4]arenes with tartaric acid ester moieties has been achieved by the reactions of tartaric ester chloroacetates with calix[4]arenes in moderate yields. All the chiral calix[4]arene derivatives are in a cone conformation according to the ¹H NMR doublet–doublet pattern of the protons of the methylene groups between the phenol rings. The results of NMR and specific rotations indicate that the molecules have C₂ symmetry with asymmetric features.     

Optically pure calix[6]tris-ammoniums: syntheses and host-guest properties toward neutral guests

[reaction: see text] Optically pure calix[6]arenes bearing chiral amino arms 4, 7, and 10 have been synthesized in high yields from the known symmetrically 1,3,5-trismethylated calix[6]arene. For both compounds 7 and 10, the key step consists of an efficient selective alkylation on the narrow rim of the calix[6]arene with Ba(OH)2 as the base. All of these chiral calix[6]tris-amines possess a similar flattened cone conformation with the cavity occupied by the methoxy groups. In contrast to 4 and 7, upon protonation, the enantiopure calix[6]arene 10 can switch to the opposite flattened cone conformation through self-assembly of its ammonium arms in an ion-paired cap which closes the cavity. As shown by NMR host-guest studies and an X-ray structure, the obtained polarized host (10 x 3H+) behaves as a remarkable endo-receptor for small polar neutral molecules. Thanks to the tris-cationic chiral binding site of 10 x 3H+, it was shown that the guests experience a chiral environment upon inclusion. Finally, the first example of enantioselective molecular recognition inside the cavity of a calix[6]arene has been evidenced with a racemic 1,2-diol guest.     

Synthesis and characterization of chiral catenanes based on rigid calix[4]arene

A new class of chiral calix[4]arene-based [2]catenanes was synthesized in excellent yields of 51-80%. They exhibit unique dynamic properties according to variable temperature NMR experiments. The enantiomeric pure (+)-catenane was prepared in 66% yield starting from (−)-calix[4]arene.     

Synthesis and chiral recognition properties of two novel chiral calix[4]arene tartaric ester derivatives

Two new chiral calix[4]arene derivatives containing tartaric acid ester moieties were synthesized. The chiral calix[4]arenes are in a ‘cone’ conformation according to NMR spectroscopy. The chiral recognition capabilities of 1–4 toward the guests, 1,2-propanediol and serine methyl ester hydrochloride (SerOMe), were investigated (¹H NMR spectroscopy). The extraction properties of compounds 1 and 2 toward selected α-amino acid methyl esters were also studied.     

上端含长链烷基的手性杯[4]芳烃合成

脱叔丁基的杯[4]芳烃与长链的叔醇或者叔氯代烷烃进行傅-克反应, 在其上端引入长链烷基. 然后在下端引入光学活性的1-苯基乙胺基团, 得到了一系列上端含长链烷基的手性杯[4]芳烃.     

Stereoselective synthesis and optical resolution of chiral calix[4]arenes with mixed ligating functionalities

Exhaustive alkylation of syn-proximal bis[(2-pyridylmethyl)oxy]calix[4]arene 1 with t-butyl bromoacetate or 2-(chloromethyl)quinoline hydrochloride in the presence of Cs₂CO₃ affords selectively a new type of inherently chiral calix[4]arenes 2a,b in the partial cone conformation. (±) 2b has been resolved into its optical antipodes by an HPLC method.     

Diastereoselective lower rim (1S)-camphorsulfonylation as the shortest way to the inherently chiral calix[4]arene

[structure: see text]. A diastereomeric mixture of chiral 25-(1S)-camphorsulfonyloxy-26-isopropoxycalix[4]arene 2a (de 15%) and 25-isopropoxy-26-((1S)-10-camphorsulfonyl)calix[4]arene 2b has been obtained by asymmetrical lower rim (1S)-camphorsulfonylation of the monoisopropoxycalix[4]arene. Pure diastereomer 2a has been obtained by simple crystallization, and its absolute configuration has been determinated by X-ray analysis. Enantiomerically pure inherently chiral 5,11-dibromo-26-isopropoxycalix[4]arene 4 has been synthesized by the upper rim dibromination of the diastereomer 2a followed by hydrolytical removal of the auxiliary camphorsulfonyl group.     

Synthesis and complexation study of calix[4]arene diamine derivative incorporated in a polymeric backbone with chiral monomers

The novel chiral polymeric compounds containing more than one calix[4]arene have been synthesized by reacting a new calix[4]arene diamine derivative with two chiral monomers. These newly prepared compounds were studied by extraction of toxic heavy metal (Cu²⁺, Co²⁺, Cd²⁺, Hg²⁺), silver and alkali metal (Na⁺, K⁺) cations from aqueous phase. It was observed that the resulting calixarene-based polymers have a good complexing ability towards silver, alkali metal and toxic heavy metal cations.     

Calix[4]arene-based bis[2]catenanes: synthesis and chiral resolution

The exclusive formation of hydrogen-bonded dimers between tetraaryl and tetratosylurea calix[4]arenes has been used to prepare a series of ten "bisloop" tetraurea calix[4]arenes 3, in which adjacent phenylurea groups are covalently linked through alpha,omega-dioxyalkane chains. This dimerization with tetratosylurea 2 as template preorganizes the alkenyl residues of tetra(m-alkenyloxyphenyl) ureas 1 and enables their selective connection in high yield (up to 95 %) by olefin metathesis followed by hydrogenation. The "bisloop" calixarenes 3 also exclusively form heterodimers with 1. Thus, in a separated metathesis/hydrogenation sequence, a series of 14 cyclic bis[2]catenanes 4, in which two calix[4]arenes are connected through their wide rims by two pairs of interlocked rings (total size 29 to 41 atoms), were prepared in yields of up to 97 %. Optical resolution of these chiral bis[2]catenanes was studied by HPLC on chiral stationary phases. The single-crystal X-ray structure of one example (4(P,10)) confirmed the interlocking rings and revealed that the hydrogen-bonded dimeric capsule of the calix[4]arene can be "completely" opened.     

Stereochemical control of calixarenes useful as rigid and conformationally diversiform platforms for molecular design

Stereochemical problems and related functions of calix[4]arenes, calix[6]arenes and their chiral derivatives have been reviewed. In p-tert-butylcalix[4]arene (1H₄) and its mono-, di-, tri-, and tetra-O-alkyl derivatives (1H₃R, 1H₂R₂,1HR₃, and 1R₄, respectively), 23 different homologues can exist (including 1H₄). We found that the OH group in the unmodified phenol unit is permeable through the calix[4]arene ring. Thus, several conformational isomers become equivalent after the ‘oxygen-through-the-annulus’ rotation of the OH group and the number of possible homologues is reduced to 13 (including 1H₃). We report in this paper the syntheses of all of these possible conformational isomers using a protection-deprotection method with a benzyl group and metal template effects. On the other hand, all possible chiral isomers that can be derived from calix[4]arene by modification of the OH groups have been systematically classified. Molecular asymmetry can be generated not only by different substituents but also by conformational isomerism. The numbers of chiral isomers are 17 for tetra-O-substituted calix[4]arenes, 9 for tri-O-substituted calix[4]arenes, 3 for di-O-substituted calix[4]arenes, and 0 for mono-O-substituted calix[4]arenes. Chiral calix[4]arenes can also be designed by the introduction of a substituent into the m-position of a phenol unit or by the use of a dissymmetric ‘stapling reaction’ in proximal phenol units. In p-tert-butylcalix[6]arene, the conformational behaviour is totally different from that in p-tert-butylcalix[4]arene. A large degree of conformational freedom remains in the framework, and both ‘oxygen-through-the-annulus rotation’ and ‘para-substituent-through-the-annulus rotation’ can take place. However, when metal cations are bound to calix[6]aryl esters, the conformation is changed to a cone type. Bridging and capping are powerful methods to immobilize the conformation of calix[6]arenes. In addition, definitive evidence for ring immobilization was obtained from the absence of racemization in the chiral calix[6]arene. A successful example of chiral recognition for α-amino acid derivatives was achieved by using chiral homooxacalix[3]arene which has ‘pseudo C₂ symmetry’. These examples indicate that calixarenes serve as rigid and conformationally diversiform platforms for the design of novel functional supramolecules.     

Synthesis of new chiral calix[4]arene diamide derivatives for liquid phase extraction of α-amino acid methylesters

The synthesis of chiral diamide derivatives of calix[4]arene from the reaction of p-tert-butylcalix[4]arene diester 1a and calix[4]arene diester 1b with various amino alcohols were reported. The ¹H and ¹³C NMR, data showed that the compounds synthesized exist in the cone conformation. The extraction study properties of these new compounds 3a,b–4a,b towards some selected α-amino acid methylesters are also reported.     

Synthesis and characterization of an inherently chiral calix[6]arene in the 1,4-alternate conformation

An inherently chiral calix[6]arene possessing a C₂-symmetric A-B-H substitution pattern was synthesized via a two step process starting from the parent hexa-t-butylcalix[6]arene. The racemic, inherently chiral compound exists as a single isomer with the 1,4-alternate conformation. The inherent chirality was confirmed by treatment of the racemic compound with Pirkle’s reagent to form diastereomeric complexes in solution.     

First enantiopure calix[6]aza-cryptand: synthesis and chiral recognition properties towards neutral molecules

The synthesis of the first enantiopure calix[6]aza-cryptand was achieved in five steps from the known 1,3,5-tris-O-methylated calix[6]arene. A ¹H NMR spectroscopic study has shown that the chiral tren cap constrains the calixarene core in a straight cone conformation ideal for host–guest chemistry applications. As a result, the tetra-protonated derivative displays remarkable host properties towards polar neutral molecules and enantioselective recognition processes have been evidenced with chiral guests.     

Synthesis and amino acid extraction abilities of chiral calix[4]arene triamides containing amino alcohol units

Herein the synthesis and extraction abilities of new d-/l-phenylalaninol substituted p-tert-butylcalix[4]arene triamide derivatives (3 and 4) towards amino acids are reported. These compounds (3 and 4) have been easily synthesized via aminolysis of p-tert-butylcalix[4]arene trimethylester (2) with d-/l-phenylalaninol in methanol-toluen solvent system at one step. The extraction properties of the prepared chiral calix[4]arene triamide derivatives (3 and 4) towards some selected amino acid methylesters are studied by liquid–liquid extraction. Results show that these chiral calix[4]arene triamide derivatives (3 and 4) exhibited a good affinity towards all amino acid species without any remarkably discrimination.