Macrocyclic Diamides Research Articles

Synthesis of New Benzo-substituted Macrocyclic Ligands Containing Pyridine or Triazole as Subcyclic Units

The macrocyclic diamides 11– 21, 42 and 43 were prepared by nucleophilic reaction of the bis phenols 22– 29 with the appropriate dihalo compounds 2, 3, 40 and 41, respectively. The macrocyclic dithiodiamides 30– 33 were obtained in good yields upon treatment of 11, 13, 15 and 17 with Lawesson's reagent. The macrocycles 61– 63 were prepared by condensation of the bis(aldehyde) 37 with the appropriate bis(aminotriazoles) 50– 54 to give the corresponding Schiff bases 56– 60 followed by NaBH 4 reduction.

Synthesis of New Benzo-substituted Macrocyclic Ligands Containing Quinoxaline Subunits

The macrocyclic Schiff bases 20– 25 were prepared by cyclocondensation of the bis aldehydes 12– 15 with the appropriate diaminoalkanes 17– 19. Reduction of the latter with NaBH 4 afforded the corresponding azacrown ethers 27– 30. Heating of the aldehydes 12– 16 in refluxing acetic acid afforded the corresponding 2,3-bis(benzofuranyl)quinoxalines 33– 37. Nucleophilic reaction of the bis phenols 45– 48, 54, 56, 57 with the appropriate dihalo compounds 1, 38 afforded the corresponding macrocyclic diamides 49– 52 and 1,ω-bis[quinoxalino(2,3- b)benzoxazepino-13-on-yl]alkanes 60, 61, respectively.

Strontium-Selective Membrane Electrodes Based on Some Recently Synthesized Benzo-Substituted Macrocyclic Diamides

Eight different recently synthesized macrocyclic diamides were studied to characterize their abilities as strontium ion carriers in PVC membrane electrodes. The electrode based on 1,13-diaza-2,3;11,12-dibenzo-4,7,10-trioxacyclopentadecane-14,15-dione exhibits a Nernstian response for Sr(2+) ions over a wide concentration range (1.0 × 10(-)(1)-3.2 × 10(-)(5) M) with a limit of detection of 8.0 × 10(-)(6) M (0.7 ppm). The response time of the sensor is ∼10 s, and the membrane can be used for more than three months without observing any deviation. The electrode revealed comparatively good selectivities with respect to many alkali, alkaline earth, and transition metal ions. It was used as an indicator electrode in potentiometric titration of carbonate ions with a strontium ion solution.

Copper(II)-Selective Membrane Electrode Based on a Recently Synthesized Macrocyclic Diamide

A recently synthesized 23-member macrocyclic diamide was used as a membrane-active component to prepare a new Cu2+-selective polymeric membrane electrode. The electrode exhibits a Nernstian response for copper(II) ions over a wide concentration range (1.0 × 10−1 to 3.2 × 10−5 M), with a limit of detection of 1.2 × 10−5 M (0.77 ppm). It has a response time <20 s and can be used for at least 3 months without any considerable divergence in potentials. The proposed membrane sensor revealed very good selectivities for Cu2+ over a wide variety of other metal ions and could be used in the pH range 3.5–6.0. It was used as an indicator electrode in potentiometric titration of copper ions with EDTA.

Zinc-selective membrane potentiometric sensor based on a recently synthesized benzo-substituted macrocyclic diamide

A new PVC membrane electrode for zinc ions based on a recently synthesized benzo-substituted macrocyclic diamide (1,13-diaza-2,3;11,12;15,18-tribenzo-4,7,10-trioxacyclononaoctane-14,19-dione) as membrane carrier was prepared. The sensor exhibits a Nernstian response for Zn 2+ over a wide concentration range (1.0×10 −1–9.0×10 −5 M). It has a response time of about 20 s and can be used for at least 3 months without any divergence. The proposed membrane sensor revealed good selectivities for Zn 2+ over a wide variety of other metal ions and could be used in a pH range of 3.0–7.0. It was successfully used for direct determination of Zn 2+ in solution and, as an indicator electrode, in potentiometric titration of zinc ions.

3-Allylsalicylaldehyde and 3-Allylsalicylic Acid Derivatives: Synthesis and Conversion to Allyl-crown Compounds as New Potential Precursors for Polymer Supported Crown Compounds

3-Allylsalicylaldehyde and methyl 3-allylsalicylate are converted in moderate to good yields into the new diallyl substituted 14–16, 23–25-membered macrocyclic crown diamides 8a–h, 10a–c, 15a,b and the 21–23-membered dithiatetraaza-crown compounds 17a–g, 18a–c.

Improved Method for the Preparation of Macrocyclic Diamides

Improved Method for the Preparation of Macrocyclic Diamides

Synthesis of new lipophilic acyclic di-ionizable polyethers, bis(crown ethers) and macrocyclic diamides

A series of new lipophilic acyclic polyethers containing two carboxylic or hydroxamic acid groups have been prepared. From lipophilic acyclic polyether dicarboxylic acids 2, 9 and 13, the bis(crown ethers) 20–25 were synthesized. From lipophilic acyclic polyether dicarboxylic acids 10–12 and 14, the new macrocyclic diamides 26–32 were prepared in high yields without the use of high dilution techniques or template effects.

A facile and convenient method for the preparation of macrocyclic diamides

AbstractA number of macrocyclic diamides have been synthesized from the reaction of a diacid dicarboxylic dichloride with primary diamino compound in the presence of magnesium oxide‐silica gel at room temperature in good yields. Using urea and thiourea as well as diamines to produce the corresponding macrocycles in the range of 52–56% yields are also included in this paper. One of the major advantages of this method is simple regeneration of inorganic solid and its reuse through several cycles without a decrease in activity.

Synthesis of chiral azamacrocycles using the bis(α‐chloroacetamide)s derived from chiral 1,2‐diphenylethylenediamine

AbstractOptically active diphenyl‐substituted tetraaza‐12‐crown‐4 diamide (10), tetraaza‐15‐crown‐5 diamide (12), tetraaza‐18‐crown‐6 diamide (11), and hexaaza‐18‐crown‐6 diamide (9) ligands were prepared by treating the appropriate secondary diamines with the (R,R)‐ and (S,S)‐ forms of 1,2‐bis(N‐methyl‐α‐chloracetamido)‐1,2‐diphenylethane (20). Macrocyclic diamides 9 and 10 were reduced to form the optically active diphenyl‐substituted hexaaza‐18‐crown‐6 (13) and tetraaza‐12‐crown‐4 (14), respectively. Reduction of macrocyclic diamide ligands 11 and 12 gave a complex mixture of products from which the desired tetraaza‐15‐crown‐5 and 18‐crown‐6 compounds could not be isolated. Dichloride 20 was prepared by treating the chiral forms of 1,2‐ diphenylethylenediamine with chloroacetic anhydride or chloroacetyl chloride. The crystal structures for the (R,R)‐form of dichloride 20 and the (S,S)‐forms of macrocycles 10 and 11 are reported.

3-Allylsalicylaldehyde and 3-Allylsalicylic Acid Derivatives: Synthesis and Conversion to Allyl-crown Compounds as New Potential Precursors for Polymer Supported Crown Compounds

3-Allylsalicylaldehyde and methyl 3-allylsalicylate are converted in moderate to good yields into the new diallyl substituted 14–16, 23–25-membered macrocyclic crown diamides 8a–h, 10a–c, 15a,b and the 21–23-membered dithiatetraaza-crown compounds 17a–g, 18a–c.

Anti-HIV activity and mechanism of action of macrocyclic diamide SRR-SB3.

The importance of cyclic compounds as anti-cancer and anti-viral agents has been recognized for some time. We have studied a series of macrocyclic amide derivatives for activity against HIV infection of T lymphocytes in-vitro. Compounds containing aromatic rings and sulphur atoms were generally active, however the selectivity was greatly enhanced when two benzene rings were bridged by a disulphide linkage to produce 7-methyl-6,7,8,9-tetrahydrodibenzo[c,k][1,2,6,9]-dithiadiazacyc lododecine-5,10-dione (SRR-SB3). This compound was studied in detail with different cell and virus infections including macrophages and chronically infected H9 cells. It was active with an EC50 (the dose affording 50% inhibition of infection) of 0.05-01 microg mL(-1) and a TC50 (concentration reducing uninfected cell growth by 50%) of 50 microg mL(-1). The compound did not inhibit protease, but seemed to act by inhibiting maturation of progeny virus, by interfering with precursor protein processing. It was synergistic with AZT (3'-azido-3'-deoxythymidine; zidovudine) when tested in-vitro. The unusual mode of action and potent anti-HIV activity in T lymphocytes and macrophages makes this compound a potential candidate for clinical trials.

ChemInform Abstract: The Synthesis of Macrocyclic Diamides and Tetramides Containing Phenol Units.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

The synthesis of macrocyclic diamides and tetramides containing phenol units

Thirteen new macrocyclic diamides and tetramides have been synthesized by reaction of methyl phenoxyacetates (readily obtained from various phenols) with α,ω-diamines in methanol as a solvent. Relationship between structure of esters and ratio of diamides to tetraamides has been investigated.

SRR-SB3, a disulfide-containing macrolide that inhibits a late stage of the replicative cycle of human immunodeficiency virus.

From a series of macrocyclic diamides possessing the disulfide linkage, only SRR-SB3, a compound that complexes with zinc, was found to inhibit human immunodeficiency virus type 1 (HIV-1; strain IIIB) replication at a concentration of 1.8 to 6.5 micrograms/ml in MT-4, CEM, and peripheral blood mononuclear cells. SRR-SB3 was toxic to MT-4 cells at a concentration of 15.9 micrograms/ml, resulting in a selectivity index of 9 in these cells. This macrolide was also effective against various other HIV-1 strains, including clinical isolates and HIV-1 strains resistant to protease inhibitors and nucleoside and nonnucleoside reverse transcriptase inhibitors. It was also active against various HIV-2 strains, simian immunodeficiency virus (strain MAC251), and Moloney murine sarcoma virus, but not against viruses other than retroviruses. In addition, the compound was found to inhibit chronic HIV-1 infections in vitro. The compound in combination with other antiviral agents, such as zidovudine, zalcitabine, and stavudine, showed an effect that was between additive and synergistic. Time-of-addition experiments indicated that SRR-SB3 acts at a late stage of the HIV-1 replicative cycle.

Synthesis and Characterization of 14-to 16-Membered Tetraazamacrocyclic Transition Metal Complexes Bearing Diamide Groups

Abstract o-Bromoaniline, primary diamines and dicarboxylic acids in a 2:1:1 molar ratio in methanol react with metals to yield [MLCl2] complexes [M = Fe(II), Co(II), Ni(II), Cu(II) and Zn(II); L = L−-L6] and was characterized by physicochemical methods such as IR, 1H NMR, EPR, UV/VIS, magnetic susceptibility, electrical conductivity and elemental analyses. All complexes are polycrystalline and are slightly soluble in DMF and MeCN and freely soluble in DMSO. All macrocyclic diamide complexes showed octahedral geometry and the electrical conductivity data agree well with the nonelectrolytic nature of the complexes.

Polarographic study of mercury complexes with some recently synthesized benzo-substituted macrocyclic diamides in binary acetonitrile + water mixtures

The complex formation of Hg 2+ ion with some benzo-substituted macrocyclic diamides in binary acetonitrile + water mixtures was studied by differential pulse polarography at 25°C. The stoichiometry and stability of the complexes were determined by monitoring the shift in the Hg 2+ differential pulse peak potential against the macrocycle concentration. In all cases studied, it was found that the stability of the resulting 1 : 1 complex decreases drastically by increasing the amount of water in the binary mixtures. The observed stability order in a given solvent mixture is discussed in terms of the cavity size, structural flexibility and nature of the substituents on the macrocyclic ring.

Synthesis and structure of 4,7,13-trioxa-1,10-diaza-5,6-benzocyclopentadecane monohydrate

4,7,13-T4ioxa-1,10-diaza-5,6-benzocyclopentadecane, C14H22N2O3·H2O (7) was synthesized by reduction of macrocyclic diamides (3) or (6). The compound crystallized in the orthorhombic space group Pbca witha=9.361(3),b=9.175(3),c=37.152(11) A. The structure was solved by direct methods and refined to anR value of 0.048 and wR of 0.038 for 1875 reflections. The molecule itself is internally hydrogen bonded by N−H...O connections. In the crystal structures water molecules form hydrogen bonds with amine nitrogen atoms of adjacent molecules.

A Convenient Method for Preparing Some New Macrocyclic Diamides

A simple and convenient method for preparing macrocyclic diamides containing two sulfur atoms or two to four oxygen atoms of various ring sizes was developed. This two-step procedure is simply composed of reacting salicyclic acid or 2-mercaptobenzoic acid with various diamines, followed by a Williamson synthesis.

High-pressure approach to the synthesis of macrocyclic diamides

Abstract A versatile and efficient route to macrocyclic amides via high-pressure synthesis is described. Application of the high-pressure technique allows obtaining the title compounds under ambient conditions. The scope and limitations of this reaction are presented.