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At least 721 records · Page 40Linked to original sources
PubMed2002

Kinetics of hydrolysis and cyclization of ethyl 2-(aminosulfonyl)benzoate to saccharin.

The cyclization of ethyl 2-(aminosulfonyl)benzoate (ASB) to give saccharin was investigated in aqueous solutions at pH between 5.2 and 9.5 and in the temperature range of 296.2-334.2 K. The initial concentration of the reactant was varied between 1.45 x 10(-5) and 3.86 x 10(-4) M. Ultraviolet spectroscopy was used to obtain the kinetic data. The reaction is acid catalyzed and follows pseudo-first-order kinetics. The experimental rate constant, k(obs), increases with temperature and pH. Its dependence on the temperature and pH is well described by: k(obs) = k1 [OH-] = [(2.52 +/- 0.9) x 10(16) exp(-20.2 +/- 1 kcalmol(-1)/RT) s(-1)][OH-] A mechanism is proposed and the half-life of ethyl ASB is calculated.

Benzoates↗
PubMed1998

MEK inhibitors: the chemistry and biological activity of U0126, its analogs, and cyclization products.

In search of antiinflammatory drugs with a new mechanism of action, U0126 was found to functionally antagonize AP-1 transcriptional activity via noncompetitive inhibition of the dual specificity kinase MEK with an IC50 of 0.07 microM for MEK 1 and 0.06 microM for MEK 2. U0126 can undergo isomerization and cyclization reactions to form a variety of products, both chemically and in vivo, all of which exhibit less affinity for MEK and lower inhibition of AP-1 activity than parent, U0126.

Animals↗
PubMedDate not supplied

An intramolecular cyclization reaction is responsible for the in vivo inefficacy and apparent pH insensitive hydrolysis kinetics of hydrazone carboxylate derivatives of doxorubicin.

Contradictory reports concerning the pH sensitive hydrolysis kinetics of certain hydrazone carboxylates of doxorubicin have appeared in this journal (Kaneko et al., Bioconjugate Chem. 1991, 2, 133. Padilla De Jesús et al., Bioconjugate Chem. 2002, 13, 453). Since the pH stability of the drug-carrier linkage in macromolecular prodrugs has a significant bearing on pharmacological efficacy, the hydrolysis kinetics of low molecular weight and polymeric doxorubicin hydrazone carboxylates were therefore reinvestigated. As observed previously, the conjugates readily release native doxorubicin at pH 5. Unexpectedly, in neutral buffer the hydrazone carboxylate conjugates do not release native doxorubicin, but instead rapidly release a doxorubicin derivative substituted at C-9 by 3,6-dihydro-1,3,4-oxadiazin-2-one with first-order kinetics (t(1/2) = 2.5 h). The proposed intramolecular cyclization reaction involving doxorubicin's C-14 hydroxyl and the carboxylate-substituted hydrazone rationalizes the seemingly anomalous hydrolysis kinetics seen for hydrazone carboxylate linked doxorubicin, and provides a possible explanation for the poor antitumor activity exhibited by polymer-doxorubicin conjugates utilizing this specific type of linkage.

Animals↗
PubMedDate not supplied

New cyclization reaction at the amino terminus of peptides and proteins.

Mild oxidation with periodate of the 1-amino-2-ol moiety of N-terminal seryl or threonyl peptides and proteins leads to a terminal aldehyde function O=CH-CO- which usually may be exploited for bioconjugate formation (e.g., via oximation with an O-alkyl hydroxylamine). We report that, when followed by a prolyl residue, the O=CH-CO- group can undergo a rapid cyclization and dehydration reaction through nucleophilic attack by the amide nitrogen of the third amino acid residue of the chain. We have characterized the resulting heterocycle, which is stable in aqueous acid, by mass spectrometry and NMR. Quantitative oximation can nevertheless be achieved in such cases by performing a one-pot oxidation-oximation without isolation of the intermediate aldehyde, as is demonstrated with cholera toxin B subunit.

Aldehydes↗
PubMed1980

A method for determining the positional isotope exchange in a nucleoside triphosphate: cyclization of nucleoside triphosphate by dicyclohexylcarbodiimide.

The preparations of [beta gamma-18O,gamma-18O3]ATP and [beta gamma-18O,beta-18O2]ATP and a procedure for studying the positional isotopic exchange method of Midelfort and Rose [Midelfort, C.F., & Rose, I.A. (1976) J. Biol. Chem. 251, 5881-5887] are described for detection of transient ATP cleavage to ADP in enzyme active sites. ATP is cyclized by reaction with dicyclohexylcarbodiimide in anhydrous pyridine to give adenosine 5'-trimetaphosphate. This rapidly undergoes ring opening on adding water to re-form ATP. This results in the randomization of the beta- and gamma-phosphates. The new gamma-phosphate is hydrolyzed to Pi by using glycerokinase and D-glyceraldehyde. Mass spectral analysis of the 18O distribution in this Pi allows the extent of positional isotopic exchange to be determined. Procedures suitable for use with GTP are also described.

Adenosine Triphosphate↗
PubMedDate not supplied

Palladium(0)-catalyzed coupling-cyclization reaction of polymer-supported aryl iodides with 1,2-allenyl carboxylic acids. Solid-phase parallel synthesis of butenolides.

In this contribution, we constructed a library of butenolides with 77 members by parallel synthesis strategy on Merrifield resin. Sixteen 2,3-allenoic acids and 12 polymer-bound aryl iodides were combined to react with each other, and then the polymer-supported products were cleaved to release butenolide derivatives. The reactions with alkyl-substituted 2,3-allenoic acids in acetonitrile afforded the corresponding products in high yields and high purities, whereas those with aryl-substituted acids in acetonitrile failed. After some reaction conditions were screened, the solid-phase reactions with aryl-substituted 2,3-allenoic acids were realized in toluene, and the products are of good purities albeit in slightly low yields. In the benzyl ether linkage, a new cleavage model was found. By adding 6 equiv of acetyl bromide, we can get single (5-oxo-2,5-dihydrofuran-3-yl)benzyl bromide other than the corresponding benzyl acetate. To further increase the diversities, a dihydropyran (DHP) linker was introduced into our combinatorial synthesis of butenolides. By reversing the addition sequence of 2,3-allenoic acids and organic base, we realized the solid-phase cyclization reaction of polymer-bound aryl iodides with the THP linkage in moderate yields and good purities. Now the library of butenolides includes (5-oxo-2,5-dihydrofuran-3-yl)benzoic acids, -aryl acetates, -benzyl bromides, -benzyl alcohols, and -phenols, which are difficult to synthesize with conventional solution methods.

4-Butyrolactone↗
PubMed2003

Diastereo- and enantioselective catalytic carbometallative aldol cycloreduction: tandem conjugate addition-aldol cyclization.

A catalytic diastereo- and enantioselective method for tandem conjugate addition-aldol cyclization is described. This methodology enables the formation of five- and six-membered ring products from aromatic and aliphatic mono-enone mono-ketone precursors. Notably, in a single manipulation, three contiguous stereogenic centers are created with high levels of relative and absolute stereocontrol.

Alcohols↗
PubMed2003

Solvent-controlled diastereoselective synthesis of cyclopentane derivatives by a [3 + 2] cyclization reaction of alpha,beta-disubstituted (alkenyl)(methoxy)carbene complexes with methyl ketone lithium enolates.

Reaction of alpha,beta-unsaturated methoxycarbene complexes 1 and 11 with methyl ketone lithium enolates 2 leads to the corresponding five-membered carbocyclic compounds 4 or diast-4 and 12. The influence of the solvent and/or cosolvent (PMDTA), which turned out to be crucial to direct the reaction to 4 or diast-4, is studied, and a tentative mechanism according to these facts is proposed. In addition, the reaction of carbene complex 1a with alkynyl methyl ketone lithium enolates can be directed to the formal [3 + 2] or [4 + 1] cyclization products by a slight variation of the reaction conditions. Finally, consecutive three-component coupling reactions with carbene complex 1a, lithium enolates 2, and aldehydes 18 to give, in a diastereoselective way, hydroxy carbonyl compounds 19 and tricyclic polyethers 20 are presented.

Aldehydes↗
PubMed2004

Enzymatic cyclization of 22,23-dihydro-2,3-oxidosqualene into euph-7-en-3beta-ol and bacchar-12-en-3beta-ol by recombinant beta-amyrin synthase.

Recombinant beta-amyrin synthase from Pisum sativum converted 22,23-dihydro-2,3-oxidosqualene, a substrate analogue lacking the terminal double bond of 2,3-oxidosqualene, into a 4:1 mixture of euph-7-en-3beta-ol and bacchar-12-en-3beta-ol. This is the first demonstration of the enzymatic formation of the baccharene skeleton with a six-membered D-ring. In the absence of the terminal double bond, the proton-initiated cyclization first generated the tetracyclic dammarenyl cation, followed by a backbone rearrangement with loss of H-7alpha leading to the formation of euph-7-en-3beta-ol, while D-ring expansion to the baccharenyl cation and subsequent 1,2-hydride shifts with H-12alpha elimination yielded bacchar-12-en-3beta-ol. It is remarkable that the formation of the anti-Markovnikov six-membered D-ring did not depend on the participation of the terminal pi-electrons.

Cyclization↗
PubMed2003

A general strategy to elisabethane diterpenes: stereocontrolled synthesis of elisapterosin B via oxidative cyclization of an elisabethin precursor.

Described is an efficient synthesis of the complex bioactive natural product, elisapterosin B, a potent in vitro inhibitor of Mycobacterium tuberculosis H37Rb. The synthesis elisapterosin B, prepared in its enantiomeric form, proceeds by a highly stereocontrolled sequence commencing with a simple glutamic acid derived compound. Pivotal steps in the sequence include (a) a pinacol-type ketal rearrangement to transfer chirality, (b) an IMDA reaction of an E,Z-diene to construct the elisabethin skeleton, and (c) a biosynthesis-inspired oxidative cyclization of the elisabethin precursor to elisapterosin B.

Anthozoa↗
PubMed2003

The synthesis of phosphaisocoumarins by Cu(I)-catalyzed intramolecular cyclization of o-ethynylphenylphosphonic acid monoesters.

Cu(I)-catalyzed intramolecular cyclization of o-ethynylphenylphosphonic acid monoethyl esters was examined, and a new class of six-membered phosphorus heterocycles was formed with high regioselectivity and good yields. The present reaction is the first example of intramolecular addition of P-OH to alkynes, which provides a convenient way to synthesize novel phosphorus heterocycles having potential bioactivities.

Alkynes↗
PubMed2004

A gene cluster encoding resistomycin biosynthesis in Streptomyces resistomycificus; exploring polyketide cyclization beyond linear and angucyclic patterns.

Resistomycin is a pentacyclic polyketide metabolite of Streptomyces resistomycificus that exhibits a variety of pharmacologically relevant properties. While virtually all bacterial aromatic polyketides can be grouped into linear and angular polyphenols, resistomycin has a unique "discoid" ring system. We have successfully identified the entire gene cluster encoding resistomycin biosynthesis by heterologously expressing a pooled cosmid library and screening for the fluorescence of the metabolite produced. The rem gene cluster exhibits several unusual features of the type II PKS involved, most remarkably a putative MCAT with highest homology to AT domains from modular PKSs. In addition, we provide the first insight into the molecular basis of a unique mode of cyclization giving rise to a discoid polyketide.

Benzopyrenes↗
PubMed2004

Highly efficient and enantioselective cyclization of aromatic imines via directed C-H bond activation.

The first highly enantioselective catalytic reaction involving aromatic C-H bond activation is communicated. Enantioselective cyclization of aromatic ketimines containing alkenyl groups tethered at the meta position of an imine directing group has been achieved using 5 mol % [RhCl(coe)2]2 and 15 mol % of an (S)-binol-derived phosphoramidite ligand. Selectivities of up to 96% ee and up to quantitative yields were obtained. Moreover, the identified catalyst system enables the intramolecular alkylation reaction to be performed at temperatures 75 degrees C lower than our previously reported achiral system. The reaction can even be performed at room temperature for one of the optimal substrates.

Carbon↗
PubMed2004

Oxonia-cope prins cyclizations: a facile method for the synthesis of tetrahydropyranones bearing quaternary centers.

A new cationic cascade reaction has been developed that produces 4-tetrahydropyranones in good yield. The reaction is based on the facile 2-oxonia Cope rearrangement of allyl-substituted oxocarbenium ions. In the presence of a more nucleophilic silyl enol ether, such systems rearrange and cyclize to produce tetrahydropyranones. The substrates were prepared by silyl ketene acetal addition to ketenes. The rearrangement is compatible with tetrasubstituted silyl enol ethers, which result in the diastereoselective introduction of quaternary centers at the C3 position of the tetrahydropyran ring. The oxonia-Cope Prins rearrangement is a versatile new route to tetrahydropyrans.

Acetates↗
PubMed2004

Mechanism and stereochemistry of enzymatic cyclization of 24,30-Bisnor-2,3-oxidosqualene by recombinant beta-amyrin synthase.

Recombinant beta-amyrin synthase from Pisum sativum converted 24,30-bisnor-2,3-oxidosqualene into a 3:1:0.2 mixture of 29,30-bisnor-beta-amyrin, 29,30-bisnorgermanicol, and 29,30-bisnor-delta-amyrin. Further, enzyme reactions with [23-13C]- and [23,23-2H]-labeled isotopomers demonstrated that the cyclization did not proceed through formation of a lupanyl primary cation with a five-membered E-ring, but an electrophilic addition of the tetracyclic C-18 cation on to the terminal double bond directly generated a thermodynamically favored pentacyclic secondary cation with a less-strained six-membered E-ring. Interestingly, the formation of the three regioisomers suggested that the absence of the terminal methyl groups resulted in a structural perturbation in the folding conformation of the E-ring of the oleanyl cation at the active site of the enzyme.

Cyclization↗