A Convenient Synthesis of 4,5-Diaryl-1,8-Dihalo-3,6-Dioxaoctanes

A kind of useful precursors for the construction of vicinal diaryl-substituted macrocycles, 4,5-diaryl-1,8-dihalo-3,6-dioxaoctanes, was readily produced by reductive coupling of aromatic carbonyl compounds with 2-haloethanols in the presence of tin powder and chlorotrimethylsilane in moderate to good yields by a one-pot procedure.     

Parallel synthesis of peptide-like macrocycles containing imidazole-4,5-dicarboxylic acid

We prepared a series of peptide-like 14-membered macrocycles containing an imidazole-4,5-dicarboxylic acid scaffold by using known coupling reagents and protecting group strategies. Yields of the purified macrocycles were poor on average, yet seemingly independent of amino acid substitution or stereochemistry. The macrocycles retain some level of conformational variability as observed by both molecular modeling and X-ray crystallography. These macrocycles represent a new class of structures for further development and for future application in high-throughput screening against a variety of biological targets.     

Synthesis of an azacrown template for phosphatidylinositol-4,5-bis(phosphate) recognition

An azacrown system has been developed for selective membrane binding of phosphatidylinositol-4,5-bis(phosphate) recognition. Neutral and cationic forms of the metacyclophane macrocycles have been synthesized by divergent routes in acceptable yields. Such diversity will be useful in identifying anion receptors that operate best at membrane interfaces.     

Synthesis of novel enantiomerically pure tetra-carbohydrazide cyclophane macrocycles

A total of twelve novel enantiomerically pure tetra-carbohydrazide cyclophane macrocycles have been synthesised in quantitative yields by reacting chiral (4R,5R)- and (4S,5S)-1,3-dioxolane-4,5-dicarbohydrazides with aromatic bis-aldehydes in a [2 + 2]-cyclocondensation reaction. The compounds show a dynamic behaviour in solution, which has been rationalized in terms of an unprecedented conformational interconversion between two conformers one stabilised by intramolecular hydrogen bonding and π-π stacking interactions.     

A new synthetic route to polyaza-crown macrocycles through the per(N-formyl)polyaza-crowns

Seven new per(N-formyl)polyaza-crown macrocycles 1-7 containing 14 to 21 ring members have been synthesized in yields of over 40% via the cyclization reaction of the appropriate per(N-formyl)polyamine 11-13 with the appropriate ditosylate, dibromide or diiodide. Three of the per(N-formyl) macrocycles 5-7 were hydrolyzed under acidic conditions to give the unsubstituted polyaza macrocycles 8-10 in yields of over 77%.     

Synthesis and studies of crowned dipyrromethenes based macrocycles

Three different meso-substituted new type of crowned dipyrromethene macrocycles were synthesized in decent yields over a sequence of four simple reaction steps using readily available precursors. The macrocycles were thoroughly characterized by HRMS as well as 1D and 2D NMR spectroscopic techniques and the structures of one of the macrocyles in its neutral form and protonated form were determined by X-ray crystallography. The crystal analysis indicated that the macrocycle was distorted in both neutral and protonated forms owing to the presence of flexible aliphatic ether chain. Absorption and electrochemical studies indicated that the properties of macrocycles were dependent on type of aryl group present at the meso-position of dipyrrin moiety of crowned dipyrromethene macrocycle. The preliminary studies indicated that the crowned dipyrromethene macrocycles can act as specific colorimetric optical sensor for Cu²⁺ ion.     

A Stable Seven‐Membered Heterocycle,Containing B,C, N,O, and P Atoms,inside a Smaragdyrin Macrocycle

Unprecedented examples of smaragdyrin macrocycles containing seven membered heterocyclic rings were synthesized under simple reaction conditions in high yields. The heterocycle formed inside smaragdyrin macrocycle is rare example of heterocycle containing five different atoms, such as B, C, N, O, and P atoms. The mixed B^III and P^V complexes of smaragdyrin macrocycles showed new structural, spectral, and electrochemical properties.     

Hydrogen-bonded aryl amide macrocycles: synthesis, single-crystal structures, and stacking interactions with fullerenes and coronene

Six hydrogen-bonded shape-persistent aryl amide macrocycles have been prepared by using one-step and (for some) step-by-step approaches. From the one-step reactions, 3 + 3, 2 + 2, or even 1 + 1 macrocycles were obtained in modest to good yields. The reaction selectivity was highly dependent on the structures of the precursors. The X-ray structural analysis of two methoxyl-bearing macrocycles revealed intramolecular hydrogen bonding and weak intermolecular stacking interaction; no column-styled stacking structures were observed. The 1H (DOSY) NMR, UV-vis, and fluorescent experiments indicated that the new rigidified macrocycles complex fullerenes or coronene in chloroform through intermolecular pi-stacking interaction. The association constants of the corresponding 1:1 complexes have been determined if the stacking was able to cause important fluorescent quenching of the macrocycles or coronene.     

Preparation of a variety of macrocyclic Di- and tetraamides and their peraza-crown analogs using the crab-like cyclization reaction

Twelve new macrocyclic di- and tetraamides have been synthesized from the reaction of a bis(α-chloroamide) with a primary amine or with a diamine. Some of these cyclic di- and tetraamides contained pendant aminoalkyl groups attached on one or more ring nitrogen atoms. Two macrocyclic dithiadiamides were prepared from the reaction of a bis(α-chloroamide) and a dimercaptan. In every case, 12-, 14- and 15-membered cyclic di- and tetraamides were isolated in good yields. The 9-, 17- and 18-membered macrocycles were prepared in lower yields. Four of the amide-containing macrocycles were reduced by diborane to the perazacrown compounds.     

Clays as a host matrix in the synthesis of organic macrocycles

A new approach for the synthesis of amide macrocycles, based on the use of organo-clay derivatives as controlling template, is proposed as an alternative to the rotaxane method. Dications of p-xylylene diamine inserted in the clay interlayer space act as molding pillars around which neutral diamine molecules are erected via hydrogen bonding and pi-pi interactions to form supramolecular arrays. Condensation of diamines in the supramolecular arrays with diacetyl dichlorides yields various tetramide macrocycles in good yields. Shape, aromaticity and dimensions of the reactants are factors affecting the condensation reaction.     

Synthesis of New Multibenzo Oxygen–Sulfur Donor Macrocycles Containing Lactams at Room Temperature

Some new oxygen–sulfur, multibenzo macrocyclic ligands containing amide groups have been prepared using the macrocyclization process with the reaction of 2,2′-thiobis-[4-methyl(2-aminophenoxy)phenyl ether] as a symmetrical diamine with appropriate dicarboxylicacid dichlorides in moderate yields. This macrocyclization led to the formation of di- and tetramide macrocycles. These reactions were routinely carried out at ambient temperature in CH₂Cl₂ as solvent in high dilution without template effect conditions. It is found that sulfur the atom affects the rigidity of the macrocycles and diastereotopicity of nuclei in the ring of these series of macrocyclic compounds.     

Non-aggregational aromatic oligoamide macrocycles

Attaching peripheral amide groups to the backbone of cyclic aromatic oligoamides 1 leads to new macrocycles 2 that show drastically changed behavior including modest yields of formation and no tendency to aggregate while maintaining a rigid backbone and a defined, guest-binding internal cavity.     

Imine- and Amine-Type Macrocycles Derived from Chiral Diamines and Aromatic Dialdehydes

The condensation of aromatic dialdehydes with chiral diamines, such as 1,2-trans-diaminocyclohexane, leads to various enantiopure or meso-type macrocyclic Schiff bases, including [2 + 2], [3 + 3], [4 + 4], [6 + 6] and [8 + 8] condensation products. Unlike most cases of macrocycle synthesis, the [3 + 3] macrocycles of this type are sometimes obtained in high yields by direct condensation without a metal template. Macrocycles of other sizes from this family can often be selectively obtained in high yields by a suitable choice of metal template, solvent, or chirality of the building blocks. In particular, the application of a cadmium(II) template results in the expansion of the [2 + 2] macrocycles into giant [6 + 6] and [8 + 8] macrocycles. These imine macrocycles can be reduced to the corresponding macrocyclic amines which can act as hosts for the binding of multiple cations or multiple anions.     

High-yielding macrocyclization conditions used in the synthesis of novel Sansalvamide A derivatives

Described are the syntheses of nine Sansalvamide A derivatives using new, high-yielding, in situ deprotection-cyclization conditions that are general for this series of macrocycles, 55% average for both steps. This is 10-fold greater than previously reported yields.     

Facile syntheses of homothia‐ and homoazacalixarenes

Decahomotetrathiacalix[6]arenes were conveniently prepared from the 2:2 cyclization reactions of bis(chloromethyl)phenol‐formaldehyde trimers with 1,2‐ethanedithiol in high yields. In contrast, the simi lar reactions of the trimers with 1,3‐propanedithiol instead of 1,2‐ethanedithiol gave 1:1 macrocycles, hexahomodithiacalix[3]arenes, in good yields. Homoazacalixarenes were also prepared from the analogous reactions using piperazines. These macrocycles adopt a cone‐like form as a preferable conformation in solution.     

Synthesis of polyaza macrocycles by palladium-catalyzed amination of 1,2-dibromobenzene and 2-bromo-1,3-dichlorobenzene

Palladium-catalyzed amination of 1,2-dibromobenzene with equimolar amounts of linear polyamines leads to the formation of polyaza macrocycles in low yields. The use of 2-bromo-1,3-dichlorobenzene as starting compound ensures considerably larger yields of the target macrocycles, and the reaction is accompanied by side formation of N-aryl- and N,N′-diaryl-substituted polyamines, as well as of cyclic oligomers. The yields strongly depend on the polyamine chain length. Reactions of excess 2-bromo-1,3-dichlorobenzene with a series of polyamines gave the corresponding N,N′-diarylpolyamines in high yields, and the latter reacted with the second polyamine molecule to form cyclic dimers. A relation between the yield of cyclic dimers and polyamine structure was revealed.     

A facile and efficient synthetic approach to novel lariat macrocyclic diamides and bis macrocyclic diamides

The hydroxy macrocycles 8, 19a‐c were prepared in 40–55% yields by reacting the dipotassium salts 2a‐c with each of epichlorohydrin ( 7 ) and bis(chloromethyl) derivative 18 . Acylation of the hydroxyl group of each of 8, 19a‐c with 2‐chloroacetylchloride ( 9 ) in DMF gave the corresponding esters 10, 20a,b . Reaction of the latter with different amines as well as phenoxides furnished exclusively the target lariat macrocycles 13a‐c, 22a‐c and 23a‐c in 60–63% and 50–55% yields, respectively. Amination of two equivalents of the chloroacetyloxy derivative 10 and 2a,b with 1 equiv. of piperazine ( 12c ) afforded the corresponding bismacrocycles 14 and 26a,b respectively, in 60–65% yields. Moreover, the novel bis(macrocycles) 27–29 were prepared in 45–50% yields, respectively, by reacting each of 20a,b with the dipotassium salts 2b, 24 and 25 respectively, in DMF.     

Synthesis of Carbohydrate Based Macrolactones and Their Applications as Receptors for Ion Recognition and Catalysis

Glycomacrolactones exhibit many interesting biological properties, and they are also important in molecular recognitions and for supramolecular chemistry. Therefore, it is important to be able to access glycomacrocycles with different sizes and functionality. A new series of carbohydrate-based macrocycles containing triazole and lactone moieties have been designed and synthesized. The synthesis features an intramolecular nucleophilic substitution reaction for the macrocyclization step. In this article, the effect of some common sulfonate leaving groups is evaluated for macrolactonization. Using tosylate gave good selectivity for monolactonization products with good yields. Fourteen different macrocycles have been synthesized and characterized, of which eleven macrocycles are from cyclization of the C1 to C6 positions of N-acetyl D-glucosamine derivatives and three others from C2 to C6 cyclization of functionalized D-glucosamine derivatives. These novel macrolactones have unique structures and demonstrate interesting anion binding properties, especially for chloride. The macrocycles containing two triazoles form complexes with copper sulfate, and they are effective ligands for copper sulfate mediated azide-alkyne cycloaddition reactions (CuAAC). In addition, several macrocycles show some selectivity for different alkynes.     

Microwave assisted cyclocondensation of dialdehydes with chiral diamines forming calixsalen type macrocycles

Microwave irradiation of various dialdehydes and chiral diamines afforded chiral macrocyclic imines in moderate to good yields. Linked dialdehydes predominantly form [2+2] macrocycles whereas dialdehydes without linkers yield [3+3] macrocycles. This is the first report of template-free synthesis of calixsalen-type macrocycles formed in shorter reaction times under microwave conditions. In all the reactions, the salts of chiral diamines were used in contrast to the free diamines normally employed.     

Arylene ethynylene macrocycles prepared by precipitation-driven alkyne metathesis

A convenient, multigram-scale synthesis of arylene ethynylene macrocycles near room temperature is described. Driven by the precipitation of a diarylacetylene byproduct, alkyne metathesis produces the desired macrocycles in one step from monomers in high yields.