Expedient synthesis of benzene tricarboxamide macrocycles derived from p-aminobenzoic acid

The synthesis of macrocycles functionalized at the periphery in a regiospecific fashion is considered challenging. This Letter describes a six-step synthesis of N-alkylated benzene tricarboxamide macrocycles derived from p-aminobenzoic acid via the iterative coupling of Fmoc-protected monomers and cyclization of the resultant linear foldamers.     

Simultaneously bound guests and chiral recognition: a chiral self-assembled supramolecular host encapsulates hydrophobic guests

Driven by the hydrophobic effect, a water-soluble, chiral, self-assembled supramolecular host is able to encapsulate hydrophobic organic guests in aqueous solution. Small aromatics can be encapsulated in the supramolecular assembly, and the simultaneous encapsulation of multiple species is observed in many cases. The molecular host assembly is able to recognize different substitutional isomers of disubstituted benzenes with ortho substitution leading to the encapsulation of two guests, but meta or para substitution leading to the encapsulation of only one guest. The scope of hydrophobic guest encapsulation is further explored with chiral natural products. Upon encapsulation of chiral molecules into the racemic host, diastereomeric host-guest complexes are formed with observed diastereoselectivities of up to 78:22 in the case of fenchone.     

Shape selectivity in the synthesis of chiral macrocyclic amides

Shape-persistent, optically-active arylamide macrocycles have been designed and approached by using a stepwise, convergent methodology. The source of chirality, an axially-chiral Binol scaffold, incorporates methoxy functionalities in the 2,2′ positions, and carboxylic functionalities in the external 3,3′ positions. The latter can be efficiently elaborated through aromatic amidation to introduce aromatic spacers of differing shapes. The peculiar arrangement of functionalities on the Binol skeleton functions as an element of rigidification of the covalent structure through the formation of stable intramolecular hydrogen bonds. When this element is counterbalanced by the use of a flexible 3,3′-diaminobiphenyl as a spacer, yields for the macrocyclization step increase to values higher than 50%. The recognition properties of this particular macrocycle have been exploited and, while they indicate modest binding affinities towards carboxylate anions, the additional stabilization of neighbouring amide functionalities suitably placed within the covalent framework induces detectable binding of proper difunctional carboxylates.     

Efficient access to new chemical space through flow--construction of druglike macrocycles through copper-surface-catalyzed azide-alkyne cycloaddition reactions

A series of 12‐ to 22‐membered macrocycles, with druglike functionality and properties, have been generated by using a simple and efficient copper‐catalyzed azide–acetylene cycloaddition reaction, conducted in flow in high‐temperature copper tubing, under environmentally friendly conditions. The triazole‐containing macrocycles have been generated in up to 90 % yield in a 5 min reaction, without resorting to the high‐dilution conditions typical of macrocyclization reactions. This approach represents a very efficient method for constructing this important class of molecules, in terms of yield, concentration, and environmental considerations.     

Self-Assembly of Quinodimethanes through Covalent Bonds: A Novel Principle for the Synthesis of Functional Macrocycles

A multiplication of functional units was accomplished in a simple fashion by the tetramerization of a quinodimethane. This principle is demonstrated by the convergent construction of a macrocyclic molecule with 16 ferrocenes and a macrocyclic molecule with 16 dendritic units at the periphery of the molecule (see scheme). FG=functional group     

Designed folding of pseudopeptides: the transformation of a configurationally driven preorganization into a stereoselective multicomponent macrocyclization reaction

The efficient synthesis of large-ring pseudopeptidic macrocycles through a multicomponent [2+2] reductive amination reaction is described. The reaction was entirely governed by the structural information contained in the corresponding open-chain pseudopeptidic bis(amidoamine) precursors, which have a rigid (R,R)-cyclohexane-1,2-diamine moiety. A remarkable match/mismatch relationship between the configurations of the chiral centers of the cyclic diamine and those of the peptidic frame was observed. The macrocyclic tetraimine intermediates have been studied in detail by NMR spectroscopy, circular dichroism (CD), and molecular modeling, and the results support the appropriate preorganization induced by the match combination of the chiral centers. We have also synthesized the corresponding open-chain bis(imine) model compounds. The structural studies (NMR spectroscopy, CD, modeling) of these systems showed an intrinsically lower reactivity of the mismatch combination, even when the product of the reaction was acyclic. In addition, a synergistic effect between the two chiral substructures for the correct folding of the molecules was observed. Finally, X-ray analysis of the HCl salt of one of the macrocycles showed an interesting pattern; the macrocyclic rings stack in columnar aggregates leaving large interstitial channels filled with water-solvated chloride anions.     

Enantioselective syntheses of candenatenins B and C using a chiral anthracene auxiliary

The asymmetric syntheses of two anticancer natural products, candenatenins B and C, are described, leading to a revision of the originally assigned stereochemistries. The syntheses follow a Diels-Alder/retro-Diels Alder strategy using a chiral anthracene auxiliary to access both targets with 90% ee. The inherent structural qualities of the auxiliary allow for both regio- and diastereoselective transformations.     

Regulated Single‐Axis Rotations of a Carbonaceous Guest in a van der Waals Complex with an Entropy Cost

In a tight host–guest complex assembled solely by nondirectional van der Waals forces, unique motions of the guest, such as solid‐state inertial rotations, emerge. The regulation of dynamic motions is an important element to be explored for novel functions of such complexes, which may be seemingly difficult to achieve because of the nondirectionality of the assembling forces. A regulated, single‐axis rotation was made possible by choosing an appropriate shape of the guest in the tubular host. Specifically, an ellipsoidal guest was made to stand along a cylinder axis of the host, which consequently resulted in single‐axis rotations of the guest in the solid. The rotational frequency was considerably high for solid‐state rotations but was suppressed to 10 GHz, which was 1/20 of the isotropic rotation of a spherical guest. In‐depth kinetic analyses quantitatively revealed that the entropy cost was a determining factor that regulated the dynamics.     

Resolution of Racemic 1,2-Dibromohexafluoropropane through Halogen-Bonded Supramolecular Helices

Halogen bonds , attractive intermolecular interactions between perfluoroalkyl bromides and bromide ions, are present in cocrystals of (−)-sparteinium hydrobromide ( 1 ) and (S)-1,2-dibromohexafluoropropane ( 2 ; shown schematically), and result in enantiopure and infinite supramolecular helices. The perfluorocarbon–hydrocarbon self-assembly allows the resolution of racemic 2 .     

Self-assembly of a new series of quadruply hydrogen bonded heterotrimers driven by the donor-acceptor interaction

This paper describes the self-assembly of a new series of heterotrimers in chloroform-d by utilizing the cooperative interaction of hydrogen bonding and donor-acceptor interaction. Compounds 1 and 11, in which an 2-ureido-4[1H]-pyrimidinone unit is connected to 34-crown-10 or 36-crown-10, were used as donor monomer, and 2 and 19, in which an 2-ureido-4[1H]-pyrimidinone unit is connected to NDI, were used as acceptor monomer, while linear compound 4, which contains two diamido-1,8-naphthyridines, was used as template. A large tri-p-(t-butyl)phenylmethoxyl group was introduced to 19 in order to compare its assembling behavior with that of 2. Mixing 4 with dimer 1·2 caused 1·2 to fully decompose and to afford 55% of ‘in-in’-oriented heterotrimer 1·4·2. Adding 4 to the solution of 2·11 or 11·19 in chloroform-d also led to full dissociation of the dimers. However, in these systems the ‘in-in’-arranged heterotrimer 2·4·11 or 11·4·19 could be produced exclusively.     

Synthesis and optical properties of (a)chiral terpyridine-ruthenium complexes

Chiral terpyridine ligands have been synthesized and characterized. By applying Ru(III)/Ru(II) chemistry, symmetrical as well as asymmetrical bis-terpyridine ruthenium(II) complexes were obtained. These materials were fully characterized and their optical properties investigated. While the chiral metal complexes revealed no Cotton effect in good solvents such as chloroform, CD-measurements in dodecane showed an effect in both ligand and MLCT regions, suggesting chirality transfer from the lateral alkyl chains to the complex core. This behavior points to the formation of supramolecular aggregates in dodecane. Furthermore, the analogous achiral ligand and its corresponding ruthenium(II) complexes were prepared.     

Self-Assembly of a Molecular Floral Lace with One-Dimensional Channels and Inclusion of Glucose

A three-dimensional network with one-dimensional channels (see picture) has been self-assembled from the nickel(II ) complex of cyclam and 1,3,5-benzenetricarboxylate in water through hydrogen-bond formation. The channels have an appropriate diameter (10.3 Å) to include D -glucose with a formation constant of K_f=(1.38±0.01)×10⁴ M ⁻¹. Under similar conditions maltose is not included.     

Self-assembly of iron TCPP (meso-tetra(4-carboxyphenyl)porphyrin) into a chiral 2D coordination polymer

Synthetic metalloporphyrin complexes are often used as analogues of natural systems, and they can be used for the preparation of high-dimensional coordination polymers. In this work, a new chiral Fe-TCPP (TCPP is meso-tetra-(4-carboxyphenyl)porphyrin) coordination compound has been synthesized and structurally characterized. The compound is 2D via coordination bonds, and it exhibits strong hydrogen bonds that connect the planar arrays forming the 3D framework. The oxidation of the original Fe^II ions to Fe^III accounts for the formation of this array, in which the topological analysis reveals a very high connectivity based on a simple extension fashion of the structure. DFT calculations have been also carried out to study the stabilization of the Fe^III-compound. This is the third example of a 2D coordination compound based on TCPP in which the dimensionality refers just to coordination bonds, and no other ligands are present in the structure.     

Synthesis of new chiral PNAs bearing a dipeptide-mimic monomer with two lysine-derived stereogenic centres

The synthesis of new chiral PNA analogues based on lysine is reported. In particular, l- and/or d-lysine-based PNA submonomers bearing two lysine side chains exactly spaced as in the dipeptide Lys-Lys were synthesized and incorporated in the middle of decameric PNA strands, obtaining four diastereomeric (LD, DL, LL and DD) lysine-based chiral PNAs. The hybridization with their complementary antiparallel DNA strand was studied by melting temperature determination and compared with the analogue achiral PNA and chiral PNAs bearing one residue with either of the two lysine enantiomers. The binding abilities were shown to be strongly dependent on the configuration of the stereogenic centres.     

Phosphinoyl-aziridines as a new class of chiral catalysts for enantioselective Michael addition

A series of new optically pure phosphine oxides containing chiral aziridine subunit were synthesized in good yields and applied as organocatalysts in asymmetric Michael reaction of various aliphatic aldehydes with β-nitrostyrene. The corresponding organocatalysts were synthesized starting from optically pure aziridines in a few simple efficient steps. The appropriate Michael adducts were obtained in most cases in very high chemical yield (up to 97%), excellent enantioselectivity (up to 98% of ee) and diastereoselectivity (up to 95:5 of dr).     

Synthesis of chiral allenes from ynamides through a highly stereoselective Saucy-Marbet rearrangement

A highly stereoselective Saucy-Marbet rearrangement using chiral ynamides and propargyl alcohols is described here. This rearrangement can be catalyzed by para-nitrobenzenesulfonic acid and leads to high diastereoselectivities for a range of different chiral propargyl alcohols and ynamides in a stereochemically intriguing matched, mismatched or indifferent manner. The stereoselective Saucy-Marbet rearrangement of ynamides provides an excellent entry to highly substituted chiral homo allenyl alcohols.     

新型环氧水解酶手性拆分环氧氯丙烷的气相色谱法

建立了一种用于快速测定生物酶转化体系中手性环氧氯丙烷的气相色谱法。采用ZKAT-ChiralB毛细管柱,FID检测器检测,内标法计算含量。(R)-环氧氯丙烷和(S)-环氧氯丙烷在0.012～0.461g/mL呈良好的线性关系,RSD为1.3%、1.7%,回收率为97.6%、101.3%。     

Syntheses of a new type of chiral phosphines from glucose

Methyl 3-deoxy-3-(diphenylphosphino)-4,6-O-benzylidene-α-D-altropyranoside (1) and methyl 2-deoxy-2-(diphenylphosphino)-4,6-O-benzylidene-α-D-altropyranoside (2) were prepared from methyl 2,3-anhydro-4,6-O-benzylidene-O-D-mannopyranoside and methyl 2,3-anhydro-4,6-O-benzyl-idene-α-D-allopyranoside,respectively,via regioselective and stcreospecific ring-opening reactions in high yields.Compounds 1 and 2 were oxidized to give the corresponding phosphine oxides (3 and 4).