Imploded bilirubins: synthesis and properties of 10-nor-mesobilirubin-XIIIα and analogs

Abstract  Six 10-nor-bilirubin analogs have been synthesized and investigated. Lacking the C(10) CH₂ group, these linear tetrapyrroles have a bipyrrole core rather than a dipyrrylmethane core and thus a different shape. Whereas the propionic acid groups of bilirubin are well engaged in intramolecular hydrogen bonding to the dipyrrinones, molecular modeling studies of the 10-nor-rubins predict that propionic acid chains are too short to engage the CO₂H hydrogen fully in intramolecular hydrogen bonding with the dipyrrinones. Butyric acid chains, however, can and do lead to a stabilized conformation with a bipyrrole dihedral angle of approximately 115°. Spectroscopic studies verify the predictions and vapor pressure osmometry indicates that the 10-nor-rubins with butyric acids are monomeric in CHCl₃. Graphical abstract  

Electrochemical synthesis and characterization of polydiphenylamine

Electrochemical oxidation of diphenylamine(DPA)in acetonitrile solution producedan adhesive conducting polydiphenylamine(PDPA)film on the electrode,which exhibited multiplecolour variation in a wide range of potential.The polymer was characterized by cyclic voltam-merry,FTIR and ESR.The results indicate that the electropolymerization of diphenylamine per-forms via the 4,4＇C—C phenyl-phenyl coupling mechanism.FTIR,ESR and conductivity mea-surements for the different states of PDPA show that polydiphenylamine can be reversibly dopedand dedoped either chemically or electrochemically.It is evidenced also that there are paramagneticspecies—polarons in PDPA supposed to be the current carrier.     

Methods of synthesis and synthetic application of α-diazomethylphosphonates

Data on methods of synthesis and reactivity of α-diazomethylphosphonic acid esters are classified. Main approaches to obtain diazomethylphosphonate ester (the Seyferth—Gilbert reagent) as well as α-substituted diazomethylphosphonates are considered. The most important reactions of α-diazomethylphosphonates are discussed: [1+2] cycloaddition to alkenes, insertion into heteroatom—heteroatom bonds, reactions with aldehydes and ketones, being of interest as preparative methods to obtain cyclopropane phosphonates, α-substituted methylphosphonic esters and alkynes, correspondingly.     

Design and synthesis of α-carboxy phosphononucleosides

Rhodium catalyzed O-H insertion reactions employing α-diazophosphonate 20 with appropriately protected thymidine, uridine, cytosine, adenosine and guanosine derivatives leads to novel 5'-phosphononucleoside derivatives. Deprotection led to a novel series of phosphono derivatives bearing a carboxylic acid moiety adjacent to the phosphonate group with potential antiviral and/or anticancer activity. The phosphononucleosides bearing an α-carboxylic acid group are envisaged as potential diphosphate mimics. Conversion to mono- and diphosphorylated phosphononucleosides has been effected for evaluation as nucleoside triphosphate mimics. Most of the novel phosphononucleosides proved to be inactive against a variety of DNA and RNA viruses. Only the phosphono AZT derivatives 56-59 showed weak activity against HIV-1 and HIV-2.     

An expedient and short synthesis of chiral α-hydrazinoesters: synthesis and conformational analysis of 1:1 [α/α-Nα-hydrazino]mers

Different α-hydrazinoesters with high optical purity have been obtained in large scale via an S_N2 protocol. A coupling reaction with a natural amino acid leads to the corresponding dimers, which have been oligomerized in order to obtain the 1:1 [α/α-N^α-hydrazino]mer series. Conformational studies show that these mixed oligomers are self-organized in solution via a succession of γ-turn and hydrazinoturn whatever the absolute configuration of the chiral carbons.     

Highly polarized enamines 1. synthesis and some properties ofβ-tetrazolylenamines

A method has been developed for the synthesis of some-tetrazolyl--nitroenamines containing various alkoxy or amino substituents in the a position. It is based on the transformation of a pyrimidine ring by sodium azide.Center for Drug Chemistry, All-Union research Institute of Pharmaceutical Chemistry (VNIKhFI), Moscow 119021 Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 976–980, July, 1994     

Total synthesis and cytotoxicity of (−)-jorumycin and its analogues

(?)-Jorumycin and its 15 C-22 analogues were prepared employing l-tyrosine as the chiral starting material via 21 steps. These analogues, along with (?)-jorumycin itself, were evaluated in vitro for cytotoxicity against HCT-8, BEL-7402, Ketr3, A2780, MCF-7, A549, BGC-823, Hela, HELF, and KB cells. The IC₅₀ values of the cytotoxicity of most of these analogs were at the level of nM, which was similar to that of (?)-jorumycin. Among these analogs including (?)-jorumycin, hippuric acid ester derivative 23 exhibited the most potent and broad-spectrum cytotoxic activity against the ten cell lines with an average IC₅₀ of 2.12 nM.     

Study on the alkylation reaction of guanine and N-acetylguanine and the synthesis of 1''''-C alkylated carba-DHPG analogues

The alkylation reaction of guanine and N-acetylguanine with model compounds such as isopropyl bromide or 4-heptyl tosylate were studied. The reaction conditions such as temperature, solvent, base, and catalyst were examined for their effects on the reaction rate, and the yield and regioselectivity of the coupling reaction. The highest yield was obtained by using DMSO as the solvent. The reaction proceeded in a homogenous manner to give higher yield of 9-N and 7-N substituted product in a mole ratio of 1:1. The ratio could be raised to 2:1 if dibenzo-18-crown-6 was used as a catalyst. Using the above procedure, three carba-DHPG analogues bearing different 1'-C alkyl side chains were synthesized.     

Total synthesis of (−) verbenalol and (−) epiverbenalol

The first asymmetric synthesis of (−) verbenalol and (−) epiverbenalol, starting from the organometallic complex (−) 1, is described.     

The synthesis and characterisation of novel dimethyl- and diphenyl-silanediolates

Dimethyl- and diphenylsilanediolates are key intermediates in the preparation of dimethyl- and diphenyl-siloxane polymers. Both dimethyl- and diphenylsilanediolates R₂Si(OM)₂, where R = Me or Ph, and M = Li, Na and K were synthesised by the reaction between dimethyl- and diphenylsilanediol and a metal or metal hydride (M/MH where M = Li, Na and K). The silanediolates were characterised by ²⁹Si, ¹³C and ¹H NMR, FTIR and mass spectroscopy.     

The synthesis and applications of α-zirconium phosphate

The synthesis of α-ZrP with a range of crystallinity is of high importance due to the different requirements in various applications.Nanosized crystalline α-ZrP is typically obtained by refluxing amorphous ZrP in concentrated H3PO4 solutions.Microcrystalline α-ZrP are obtained by direct precipitation in the presence of either HF or oxalic acid which are used as complexing agents for zirconium.These larger crystals are useful as ion-exchangers in column-type applications as the back pressure can be significantly reduced.A novel minimalistic synthesis that is green,simple and fast is highlighted in this review.Both nano-sized and micro-sized α-ZrP can be prepared via this protocol to meet many potential applications.Applications of α-ZrP in ion-exchange,catalysis,lubricants,intercalation hosts,polymer fillers and fire retardants are discussed.     

Enantiodivergent synthesis of (+)- and (−)-isolaurepan

The enantiodivergent synthesis of (+)-and (?)-isolaurepan was achieved from a common chiral template easily available from tri-O-acetyl-d-glucal, using as key step a diastereoselective thermal Claisen rearrangement, combined with a ring expansion reaction using trimethylsilyldiazomethane.     

Total synthesis of α-1C-galactosylceramide, an immunostimulatory C-glycosphingolipid, and confirmation of the stereochemistry in the first-generation synthesis

A nonisosteric α-C-glycoside analogue of KRN7000 (α-1C-GalCer, 1) was reported to induce a selective type of cytokine release in human invariant natural killer cells in vitro. We report here a very concise synthetic route to 1 and its analogue 1'. The key steps include olefin cross-metathesis, Sharpless asymmetric epoxidation, and epoxide opening by NaN(3)/NH(4)Cl. Inversion of configuration at the amide-bearing carbon in the phytosphingosine backbone constructed by epoxide opening in our previous synthesis of 1 was verified, indicating that remote group participation is not involved during the epoxide-opening reaction.     

synthesis and properties of β-brominated metal complexes of meso-triphenylcorrole

Spectral properties and chemical stability of Mn(III), Mn(IV), Fe(III), Fe(IV), and Cu(III) complexes of β-octabromotriphenylcorrole [(β-Br)₈(ms-Ph)₃Cor], synthesized from β-unsubstituted compounds by their reaction with molecular bromine, were studied. Cyclic voltammetry, electron microscopy, and X-ray spectral microanalysis were used to obtain electrochemical characteristics of metal corroles M(β-Br)₈(ms-Ph)₃Cor and gain insight into the surface texture of active catalysts on the basis of metal corroles. The electron-acceptor β-bromine substitution in the MCor macrocycle shifts the equilibrium in electron-donor solvents to lower oxidation states of the metals and also stabilizes manganese and destabilizes copper complexes in the protondonor medium HOAc-H₂SO₄. The electrocatalytic activity of the complexes in the reduction of molecular oxygen depends on the nature of the ligand and increases in the order Mn ≤ Cu ? Fe in the case of β-octabrominated macrocycles. The character of distribution of active centers on the surface of the catalysts was established for the first time.     

Organocatalytic synthesis of α-hydroxy and α-aminophosphonates

A new and highly flexible procedure is described for the synthesis of α-amino- and α-hydroxy phosphonates. In the presence of a catalytic amount of oxalic acid (10 mol %), trimethyl phosphite reacts with aldehydes or imines (generated in situ from an aldehyde and an amine) to yield the corresponding coupled products in good yield.     

Toward the synthesis of 1′E-isomer of ent-hyptenolide

A short total synthesis of a diacetoxylated E,E-diene lactone ent-hyptenolide, was achieved involving from Phosphonate and cis-butene 1,4-diol. Brown Asymmetric allylation, Acrylation, Acetylation, Ring-closing metathesis as the key steps has been described. Moreover, the biological activity of ent-hyptenolide was evaluated on HeLa, A549, IMR32, and MDA-MB231 cancer cell lines. The ent-hyptenolide selectively and potently inhibited the growth of IMR32 cell line.     

Neat synthesis and antioxidant activity of α-aminophosphonates

A simple, efficient, and environmentally benign method for a three-component reaction of an amine, an aldehyde and diethyl phosphite catalyzed by Amberlyst-15 has been developed to afford α-amino phosphonates in high yields and short reaction times under solvent-free reaction conditions using microwave irradiation. The major advantages of the present method are inexpensive, ecofriendly and reusable catalyst and also studied their antioxidant activity of synthesized compounds.