Synthesis and enantioselective fluorescent sensors for amino acid derivatives based on BINOL

Four novel derivatives of 1,1′-bi-2-naphthol have been prepared and the structures of these compounds characterised by IR, MS, ¹H and ¹³C NMR spectroscopy and elemental analysis. The enantioselective recognition of these sensors has been studied by fluorescence titration and ¹H NMR spectroscopy. The sensors exhibited different chiral recognition abilities towards N-Boc-protected amino acid anions and formed 1:1 complexes between the host and the guest. Sensors exhibit excellent enantioselective fluorescent recognition ability towards the amino acid derivatives.     

Optically active dendrimers with a binaphthyl core and phenylene dendrons: light harvesting and enantioselective fluorescent sensing

Optically active dendrimers containing a 1,1'-binaphthyl core and cross-conjugated phenylene dendrons were synthesized and characterized. The chiral optical properties of these phenylene-based dendrimers are different from the previously reported phenyleneethynylene-based dendrimers probably because of the increased steric interaction between the adjacent phenylene units. UV and fluorescence spectroscopic studies demonstrate that the energy harvested by the periphery of the dendrimers can be efficiently transferred to the more conjugated core, generating much enhanced fluorescence signal at higher generation. The fluorescence of these dendrimers can be quenched both efficiently and enantioselectively by chiral amino alcohols. The energy migration and light-harvesting effects of the dendrimers make the higher generation dendrimer more sensitive to fluorescent quenchers than the lower ones. Thus, the dendritic structure provides a signal amplification mechanism. These materials are potentially useful in the enantioselective recognition of chiral organic molecules.     

Highly enantioselective fluorescent sensor for chiral recognition of amino acid derivatives

A highly enantioselective fluorescent sensor, containing benzylaminomethyl groups at 3,3′-position of 1,1′-bi-2-naphthol (BINOL), has been used to conduct the chiral recognition of α-amino acid derivatives. It is observed that one enantiomer of N-Boc-proline can increase the fluorescence intensity of the binaphthyl fluorophores by over 57-fold, while the other enantiomer can cause only sixfold fluorescence enhancement. Such unusually highly enantioselective response demonstrates that this sensor is potentially useful in the enantioselective recognition of amino acid derivatives.     

Cholic acid-based fluorescent probes for enantioselective recognition of trifunctional amino acids

The ditopic fluorescent photoinduced electron transfer (PET) amino acid sensory probes and were designed and synthesized from cholic acid. To confer the probes with specific binding ability, an amidothiourea moiety and a cyclic diamino-chiral receptive site were introduced on the C17 side chain and the C7 and C12 hydroxyl pendants, respectively. In acetonitrile, the probes demonstrated differential binding toward trifunctional amino acids like serine, lysine, threonine and tyrosine against other simple amino acids. Enantioselectivities (KD/KL) of up to 8.9 and sensitivities in the micromolar range with the probes were observed for trifunctional amino acids.     

Optically active N-hydroxytartrimides for enantioselective peptide synthesis

Preparations of optically active N-hydroxytartrimides were achieved. 1,3,4-Trihydroxysuccinimide ester of Z-L-alanine and 1-hydroxy-3,4-diacetoxysuccinimide ester of Z-D-alanine were allowed to react with D,L-alaninate to produce L-L form and D-D form of Z-Ala-Ala-OEt respectively (optical yield 100%).     

Furo-fused BINOL based crown as a fluorescent chiral sensor for enantioselective recognition of phenylethylamine and ethyl ester of valine

A furo-fused BINOL based chiral crown was developed as an enantioselective chiral sensor for phenylethylamine and ethyl ester of valine. Fusion of furan to BINOL has resulted in a highly stereo-discriminating backbone for the chiral crown developed. This chiral crown exhibited a fluorescence enhancement difference of 2.97 times between two enantiomers of phenylethylamine and 2.55 times between two enantiomers of ethyl ester of valine. The ratio of association constants for two diastereomeric complexes of two enantiomers of phenylethylamine was found to be 11.30, and the ratio for two enantiomers of ethyl ester of valine was 7.02.     

Highly enantioselective fluorescent recognition of amino acid derivatives by unsymmetrical salan sensors

Novel unsymmetrical salan fluorescent sensors 2a and 2b have been designed and synthesized. The chiral recognition of N-Boc-protected amino acids by 2a and 2b has been investigated. Sensor 2a possesses higher sensitivity and enantioselectivity than sensor 2b does. Job analysis and nonlinear regression results show that 2a can form a 1:1 stoichiometric complex with a N-Boc-protected amino acid. The obtained response selectivities and the association constants indicate that 2a is a highly enantioselective and sensitive fluorescent sensor toward N-Boc-protected amino acids.     

Chiral amino alcohols bound to diimines, diamines and dendrimers as chiral ligands for the enantioselective ethylation of N-diphenylphosphinylimines

Chiral diimines, diamines and dendrimers possessing 2, 4 and 8 ephedrine derivatives are utilized as chiral ligands for the enantioselective addition of diethylzinc to N-diphenylphosphinylimines to afford enantiomerically enriched N-diphenylphosphinylamines in up to 93% e.e.     

Optically active dendrimers based on the planar chiral ferrocene core

The new planar chiral racemic and enantiomerically enriched Frechet-type dendrimers of the first and second generations bearing one and two branches and 1,2-disubstituted ferrocene as the core moiety were synthesized. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1220–1222, June, 2008.     

Enantioselective fluorescent recognition of amino alcohols by a chiral tetrahydroxyl 1,1'-binaphthyl compound

The tetrahydroxyl derivative of BINOL, (S)- or (R)-1, and its analogues are synthesized. (S)- or (R)-1 can be used to conduct the enantioselective recognition of chiral amino alcohols. In comparison with BINOL, the two additional hydroxyl groups of (S)- or (R)-1 have increased the binding of this compound with the amino alcohols and significantly improved the fluorescence quenching efficiency. The fluorescence responses of (S)- or (R)-1 toward amino alcohols are compared with those of its analogues (R)-4 and (R)-6. It shows that the interaction of the central naphthyl hydroxyl groups of (S)- or (R)-1 with the substrates is responsible for the observed fluorescence quenching, and the two additional alkyl hydroxyl groups increase the quenching efficiency.     

A chiral ketone for enantioselective recognition of 1,2-amino alcohols

A novel auxillary chiral ketone has been designed, synthesized, and used to enantioselectively recognize 1,2-amino alcohols. This work proves that the keto group can serve as a chiral recognition center by imine formation supported by resonance assisted hydrogen bonding (RAHB).     

A novel chiral terpyridine macrocycle as a fluorescent sensor for enantioselective recognition of amino acid derivatives

Terpyridine macrocycle 1 is shown to be a strong chelating agent for organic ammonium salts and also a useful chromophore in fluorescent sensing. It exhibits very good enantioselectivity (K(obs)(S)/K(obs)(R)= 3.8) in chiral discrimination of alpha-phenylglycine methyl ester hydrochloride (PhEtOMe).     

Enantioselective fluorescent recognition of mandelate by substituted BINOL in aqueous solutions

The fluorescent photo-induced electron transfer chemosensors (R)-1, (R)-2, (S)-1 and (S)-2 based on the 3,3′-positions of 1,1′-bi-2-naphthol were designed for their recognition of mandelate. The binding properties for mandelate were examined by the fluorescence spectra. The high fluorescence sensitivity and enantioselectivity make compound (R)-2 a practically useful sensor for the recognition of mandelate in CH₃OH/H₂O system (1:1, 0.01 M Tris–HCl buffer, pH 7.4).     

Effects of ring substituents on enantioselective recognition of amino alcohols and acids in uryl-based binol receptors

The uryl-based binol aldehyde, (S)-2-hydroxy-2′-(3-phenyluryl-benzyl)-1,1′-binaphthyl-3-carboxaldehyde (1), binds 1,2-amino alcohols and amino acids stereoselectively by reversible formation of imine bond. Hydrogen bond (between uryl group and alcohol -OH moiety) plays an important role in the stereoselectivity of amino alcohols. Hence, any substituents on phenyl group in 1 are expected to affect H-bond ability of uryl group. To study the effects of ring substituents on the stereoselective recognition of amino alcohols, (substituted phenyl)uryl-based chiral binol receptors have been prepared. The receptors with electron-donating X substituents have been synthesized from (S)-2-methoxymethoxy-2′-hydroxy-1,1′-binaphthyl-3-carboxaldehyde and X-phenyluryl-benzyl bromide. The receptors with electron-withdrawing Y substituents, however, required a different synthetic strategy including transformation of an aldehyde to alcohol. The incorporation of the electron withdrawing groups slightly accelerated the stereoselective recognition property of the receptor. Though the acceleration is not so remarkable, this work demonstrates the versatile derivatization of 1 in achieving higher stereoselective recognition of 1,2-amino alcohols and stereoconversion of l-amino acids to d-amino acids.     

Enantioselective fluorescent sensors for amino acid derivatives based on BINOL bearing benzoyl unit

The derivatives of BINOL, (S)-1 and (R)-1, and their analogues have been prepared and the structures of these compounds have been characterized by IR, MS, ¹H, and ¹³C NMR spectroscopy and elemental analysis. The enantioselective recognition of these receptors has been studied by fluorescence titration and ¹H NMR spectroscopy. The receptors exhibited different chiral recognition abilities toward some enantiomers of chiral materials and formed 1:1 complexes between host and guest. Receptor (S)-1 or (R)-1 exhibits excellent enantioselective fluorescent recognition abilities toward amino acid derivatives.     

Chiral ferrocenyl amino alcohols for enantioselective additions of diethylzinc to aldehydes

Optically active ferrocenyl amino alcohols have been prepared from commercially available l-alaninol, l-leucinol and l-valinol. They have been utilized as chiral ligands in the catalytic addition of diethylzinc to aldehydes. The influence of the substituents on the stereogenic centers of the ligand has been studied. Enantioselectivities up to 95% have been obtained.     

Highly enantioselective synthesis of a fluorescent amino acid

A high enantiomeric excess (>99.5%) synthesis of 2-amino-3-(7-methoxy-4-coumaryl) propionic acid ( Amp) is described. The two step synthesis route of this non-proteinogenic amino acid includes an oxazinone derivative as glycine enolate, which is alkylated with the fluorogenic group.     

Trifluoromethylated amino alcohols as chiral ligands for highly enantioselective Reformatsky reaction

The enantioselective Reformatsky reaction of PhCHO was achieved by the use of trifluoromethylated amino alcohols as chiral ligands to afford the corresponding optically active β-hydroxy ester with up to 90% ee.     

Catalytic enantioselective borane reduction of arylketones with pinene-derived amino alcohols

Both cis- and trans-1,2-amino alcohols 5 and their N-alkylated derivatives 6 were prepared from (−)-α-pinene 7 as chirality source and utilized in asymmetric borane reduction of arylketones 12 employing a one-pot multi-substrate screening. The oxazaborolidine catalysts were generated in situ from amino alcohols 5 and 6 and trimethyl borate.     

Optically active propargylic alcohols from d-xylose useful precursors for LTB4 synthesis

Using D-Xylose as a source of chirality at C-5 and C-12 in LTB₄, an efficient synthesis of the optically active propargylic alcohols A and B, chiral precursors for the LTB₄ synthesis, has been achieved.