6250-80-2Relevant academic research and scientific papers
Synthesis and reactivity of 2-thionoester pyrroles: A route to 2-formyl pyrroles
Kim, Min Joon,Gaube, Sophie M.,Beh, Michael H. R.,Smith, Craig D.,Thompson, Alison
, p. 31773 - 31780 (2019/10/19)
2-Functionalised pyrroles exhibit considerable synthetic utility. Herein, the synthesis and reactivity of 2-thionoester (-C(S)OR) pyrroles is reported. 2-Thionoester pyrroles were synthesised using a Knorr-type approach from aliphatic starting materials. 2-Thionoester pyrroles were reduced to the corresponding 2-formyl pyrroles, or the deuterated formyl variant, in one step using RANEY nickel, thereby removing the need for the much-utilised hydrolysis/decarboxylation/formylation steps that are typically required to convert Knorr-type 2-carboxylate pyrroles into 2-formyl pyrroles. 2-Thionoester pyrroles proved tolerant of typical functional group interconversions for which the parent 2-carboxylate pyrroles have become known.
A new synthesis of symmetric boraindacene (BODIPY) dyes
Wu, Liangxing,Burgess, Kevin
supporting information; experimental part, p. 4933 - 4935 (2009/06/06)
BODIPY dyes were synthesized from pyrrole-2-carbaldehyde derivatives in high yields; this constitutes a new approach to this dye framework. The Royal Society of Chemistry.
Syntheses of per-15N labeled etioporphyrins I-IV and a related tetrahydrobenzoporphyrin for applications in organic geochemistry and vibrational spectroscopy
Lash, Timothy D.,Chen, Shaohua
, p. 11577 - 11600 (2007/10/03)
Nitrogen-15 labeled pyrroles have been prepared from commercially available 15N glycine or sodium nitrite using the Barton-Zard, Knorr, and Kleinspehn approaches. These pyrroles were used as intermediates in the synthesis of per-15N labeled porphyrins needed for the analysis and assignment of vibrational spectra for sedimentary porphyrins. Etioporphyrin-I was prepared via pyrromethene intermediates, while etioporphyrins II-V and a related tetrahydrobenzoporphyrin were synthesized via stepwise routes involving the copper(II) mediated cyclization of a,c-biladienes as the key step. Detailed analyses of both the proton and carbon-13 NMR spectra provide nitrogen-15 coupling constants for these important structures.
Normal and abnormal heme biosynthesis. 1. Synthesis and metabolism of di- and monocarboxylic porphyrinogens related to coproporphyrinogen-III and harderoporphyrinogen: A model for the active site of coproporphyrinogen oxidase
Lash, Timothy D.,Mani, Ukti N.,Drinan, Martin A.,Zhen, Chun,Hall, Troii,Jones, Marjorie A.
, p. 464 - 477 (2007/10/03)
Coproporphyrinogen oxidase (copro'gen oxidase), which catalyses the conversion of coproporphyrinogen-III via a monovinylic intermediate to protoporphyrinogen-IX, is one of the least well understood enzymes in the heme biosynthetic pathway. To develop a model for the substrate recognition and binding recognition for this enzyme, a series of substrate analogues were prepared with two alkyl substituents on positions 13 and 17 in place of the usual propionate residues. Although the required substrate probes are porphyrinogens (hexahydroporphyrins), the corresponding porphyrin methyl esters were initially synthesized via a,c-biladiene intermediates. These were hydrolyzed and reduced with 3% sodium amalgam to give the unstable porphyrinogens needed for the biochemical investigations. These modified structures were metabolized by avian preparations of copro'gen oxidase to give monovinylic products, but the second propionate residue was not further metabolized. In three cases, the metabolites were isolated and further characterized by proton NMR spectroscopy and mass spectrometry. When methyl or ethyl groups were placed at the 13 and 17 positions, the resulting porphyrinogens were very good substrates (although the ethyl version, mesoporphyrinogen-VI, gave slightly better results), but when propyl units were introduced metabolism was significantly inhibited and the butyl- substituted structure was only slightly transformed after long incubation periods. These results suggest the presence of an active site lipophobic region near the catalytic site for copro'gen oxidase. The observation that the related 3-vinyl- and 3-ethylporphyrinogens with 13,17-diethyl substituents were not substrates for this enzyme confirmed the need for a second propionate residue to hold the substrate in place at the catalytic site.
Stable 4E-dipyrrinones
Boiadjiev, Stefan E.,Lightner, David A.
, p. 10871 - 10886 (2007/10/03)
Dipyrrinones formed by DBU and n-Bu3P-promoted condensation of 5-p- toluenesulfonylpyrrolinones with pyrrole 2-aldehydes, gave high yields of product with predominantly the E-configuration when the aldehyde had a 5- carboethoxy group. The 4E-dipyrrinones were readily purified by chromatography and were stable in solutions shielded from light.
Synthesis and biological evaluations of 3-substituted indolin-2-ones: A novel class of tyrosine kinase inhibitors that exhibit selectivity toward particular receptor tyrosine kinases
Sun, Li,Tran, Ngoc,Tang, Flora,App, Harald,Hirth, Peter,McMahon, Gerald,Tang, Cho
, p. 2588 - 2603 (2007/10/03)
3-Substituted indolin-2-ones have been designed and synthesized as a novel class of tyrosine kinase inhibitors which exhibit selectivity toward different receptor tyrosine kinases (RTKs). These compounds have been evaluated for their relative inhibitory properties against a panel of RTKs in intact cells. By modifying the 3-substituted indolin-2-ones, we have identified compounds which showed selective inhibition of the ligand- dependent autophosphorylation of various RTKs at submicromolar levels in cells. Structure-activity analysis for these compounds and their relative potency and selectivity to inhibit particular RTKs has determined that (1) 3- [(five-membered heteroaryl ring)methylidenyl]indolin-2-ones are highly specific against the VEGF (Flk-1) RTK activity, (2) 3-(substituted benzylidenyl)indolin-2-ones containing bulky group(s) in the phenyl ring at the C-3 position of indolin-2-ones showed high selectivity toward the EGF and Her-2 RTKs, and (3) the compound containing an extended side chain at the C- 3 position of the indolin-2-one (16) exhibited high potency and selectivity when tested against the PDGF and VEGF (Flk-1) RTKs. Recent published crystallographic data for two of these 3-substituted indolin-2-ones provides a rationale to suggest that these compounds may bind in the ATP binding pocket of RTKs. The structure-activity analysis supports the use of subsets of these compounds as specific chemical leads for the development of RTK- specific drugs with broad application for the treatment of human diseases.
Thermochemistry of substituted pyrroles
Berezin, M. V.,Semeikin, A. S.,V'yugin, A. I.,Krestov, G. A.
, p. 449 - 453 (2007/10/02)
The heats of solution of a series of substituted pyrroles in benzene, carbon tetrachloride, chloroform, DMF, and pyridine were measured by a calorimetric method at 298.15 K.The influence of substituents in the pyrrole molecule on the energy parameters of solvation by organic solvents is discussed.
Synthesis and Characterisation of the C30-De-ethylaetioporphyrin Present in Petroleum
Clewlow, Paul J.,Jackson, Anthony H.
, p. 1925 - 1936 (2007/10/02)
The four de-ethyl analogues of the relatively ubiquitous and biogenetically significant petroporphyrin aetioporphyrin III (3a-d) have been synthesized utilising the ac-biladiene route.A reversed-phase HPLC method of separating a mixture of the four synthe
The total synthesis of chlorophyll a
Woodward, Robert Burns,Ayer, William A.,Beaton, John M.,Bickelhaupt, Friedrich,Bonnett, Raymond,Buchschacher, Paul,Closs, Gerhard L.,Dutler, Hans,Hannah, John,Hauck, Fred P.,Ito, Sho,Langemann, Albert,Le Goff, Eugene,Leimgruber, Willy,Lwowski, Walter,Sauer, Juergen,Valenta, Zdenek,Volz, Heinrich
, p. 7599 - 7659 (2007/10/02)
The total synthesis of chlorophyll a starting from Knorr's pyrrole (1) is described with full experimental detail. Forty six stages are involved to reach the target molecule, chlorin e6 trimethyl ester (46), from which the preparation of chlorophyll a has already been described. The four pyrroles which are required for rings A, B, C and D are elaborated largely by known reactions, although with considerable improvements. These pyrroles are manipulated to give two dipyrrin derivatives: a left-hand component (26, comprising rings A and D) and a right-hand component (the thioaldehyde 31, comprising rings B and C). These are brought together in a carefully controlled, stepwise, condensation to give a single porphyrin product (35) in 50% yield. This synthesis of an unsymmetrically-substituted porphyrin bearing an electron-withdrawing substituent and a meso-substituent is seen as a very considerable advance, both in conceptual and practical terms, over earlier approaches. During the course of the closure of the macrocycle, intermediates which exemplify a new group of dihydroporphyrins, the phlorins (e.g. 34), are recognised. Eleven steps remain. The porphyrin (35) is shown to undergo dehydrogenation (again via a phlorin intermediate) on brief treatment with acetic acid in air to give the meso-crylic acid derivative (36), which in acetic acid under nitrogen at 110° slowly reaches equilibrium with the purpurin (37). The introduction of the reactive vinyl group at C-3 has been delayed until this point in the synthesis. Photo-oxygenation of the product, the vinylpurpurin (38), cleaves the cyclopenteno-ring giving the methoxalylpurpurin (39). A reverse Claisen reaction now generates the methoxylactone, rac-isopurpurin 5 methyl ester (40), the first substance in this synthetic series which can be compared with a sample (albeit optically active) derived from natural chlorophyll a. rac-Isopurpurin 5 methyl ester (40) is hydrolysed to the lactol, chlorin 5 (41), which is resolved (diastereoisomeric salts with quinine). The less soluble salt gives synthetic act-chlorin 5, identical with a sample of natural provenance. Diazomethane treatment of the free acid (42) yields purpurin 5 dimethyl ester (43), again identical with the naturally-derived compound. Treatment with hydrogen cyanide in triethylamine leads to the cyanolactone (44), reductive cleavage and methylation of which give the chlorin e6 nitrile (45). Methanolysis of this furnishes synthetic crystalline chlorin e6 trimethyl ester (46), identical (mp, mixed mp, electronic spectrum, infra red spectrum) with a naturally-derived sample, so completing the total synthesis.
The Chemistry of Pyrrolic Compounds. LXI Petroporphyrins from the Julia Creek Oil Shale: Further Evidence for the Derivation of Aetiotype Petroporphyrins from Chlorophyll
Clezy, Peter S.,Fookes, Christopher J. R.,Prashar, Jognandan K.
, p. 775 - 786 (2007/10/02)
The synthesis of the porphyrins (2c-j) has been achieved by the oxidative cyclization of appropriately substituted biladienes-ac.The availability of authentic material has allowed the finalization of the structure of a series of aetiotype fossil porphyrins which vary in substitution pattern at positions 3 and 13.All combinations of H, Me and Et at these positions have now been isolated from natural sources.This points to a common precursor, possibly a divinylporphyrin, and strengthens the belief that the chlorophylls are the prime source of the petroporphyrins.A vinyl group, or a close derivative, is found at position 3 of all chlorophylls while fragmentation of the ubiquitous isocyclic ring of the chlorophylls could yield the vinyl group at position 13.
