Acylamino Substituents Research Articles

Unexpected Reaction Promoted by NH+···O=Mo Hydrogen Bonds in Nonpolar Solvents

A new synthetic method using [MoIV(S‐tBu)4], 1,2‐benzenedithiol containing bulky hydrophobic acylamino substituents, 3,6‐[(4‐tBuC6H4)3CCONH]2C6H2‐1,2‐(SH)2 (LH2), a tertiary amine [R3N = Et3N or 2,6‐lutidine (Lu)], and an equimolar amount of water afforded (R3NH)2[MoIVO(L)2] [(R3NH)2[1]]. Each compound formed a strong NH+···O=Mo hydrogen bond between the tertiary ammonium cation and the terminal oxo ligand in toluene, which unexpectedly promoted the one‐electron oxidation of MoIV by lutidinium ion or 0.5 equiv. Me3NO to produce [MoVO(L)2]–. In contrast, in polar solvents, typical oxygen atom transfer (OAT) from Me3NO to [1]2– was observed. A possible mechanism is presented and the role of the hydrogen bond in molybdenum enzymes is discussed.

A Synthetic GFP-like Chromophore Undergoes Base-Catalyzed Autoxidation into Acylimine Red Form

Fluorescent proteins are widely used in modern experimental biology, but much controversy exists regarding details of maturation of different types of their chromophores. Here we studied possible mechanisms of DsRed-type red chromophore formation using synthetic biomimetic GFP-like chromophores, bearing an acylamino substituent, corresponding to an amino acid residue at position 65. We have shown these model compounds to readily react with molecular oxygen to produce a highly unstable DsRed-like acylimine, isolated in the form of stable derivatives. Under the same aerobic conditions an unusual red-shifted imide chromophore--a product of 4-electron oxidation of Gly65 residue--is formed. Our data showed that GFP chromophore is prone to autoxidation at position 65 Cα by its chemical nature with basic conditions being the only key factor required.

Prediction of bond length variation in classical β-lactam structures and enzymatic ring instability

Comparison of intrinsic, solvational, and enzymatic rates of β-lactam ring opening allows rate enhancement due to specific enzyme interactions with given β-lactam moieties to be identified and modeled. Enzymatic rates of β-lactam ring opening may be derived from potency data and are briefly reviewed. For widespread comparison with intrinsic instabilities, convenient criteria for accurate estimation of the latter are required. The conditions under which differences in intrinsic instabilities of β-lactams correlate closely with their ground-state properties have been defined. Theoretical prediction of substituent effects in β-lactam structures requires geometry optimization if accuracy with the biological instability data over even moderate ranges of activity is to be maintained. The β-lactam amidic C-N bond length is a powerful indicator of intrinsic ring instability. The contributions of the ring nuclei to enzymatic stability in classical β-lactam structures correlate with the predicted C-N bond lengths for both STO-3G and 4-31G bases to ˜0.4 kcal. This accuracy corresponds to a bond length sensitivity of ± 0.004 A. The limits of convergence of the theoretical estimates are of this order. The relative theoretical amidic C-N bond lengths offer a more precise scale for ranking intrinsic β-lactam instabilities than one employing experimental X-ray quantities, with their associated perturbations from crystal forces. A specific interaction of 6/7 acylamino substituents in penicillins and cephalosporins with pbp I enzymes is identified.

Synthesis and Biological Evaluation of 2-, 3-, and 4-Acylaminocinnamyl-Nhydroxyamides as Novel Synthetic HDAC Inhibitors

A new series of 2-, 3-, and 4-acylaminocinnamyl-N-hydroxyamides 1-3 have been prepared, and their anti-HDAC (against maize HD2, HD1-B, and HD1-A enzymes) activities have been assessed. Cinnamyl-hydroxyamides bearing acylamino substituents at the C2 position of the benzene ring (compounds 1a-g) showed very low HDAC inhibiting activities, with IC(50) values in the high micromolar range. By shifting the same acylamino groups from C2 to C3 (compounds 2a-g) as well as C4 (compounds 3a-f) position of the benzene ring, a number of highly potent HDAC inhibitors have been obtained. In the anti-HD2 assay 3c (IC(50) = 11 nM) was the most potent compound, being >11600-, 4.5-, and 10-fold more potent than sodium valproate, SAHA, and HC-toxin, respectively, and showing the same activity as trapoxin. HD1-B and HD1-A assays have been performed to screen the inhibitory action of 1-3 against mammalian class I (HD1-B) and class II (HD1-A) HDAC homologous enzymes. From the corresponding IC(50) data, a selectivity ratio has been calculated. In general, compounds 1-3 showed no or little selectivity towards the class II homologue HD1-A, the most selective being 2a with class II selectivity ratio = 4.3. About the inhibitory potency, the 4-(2-naphthoylamino)cinnamyl-N-hydroxyamide 3f showed the highest inhibiting effect against the two enzymes (IC(50-HD1-B) = 36 nM; IC(50-HD1-A) = 42 nM). Selected 2 and 3 compounds will be evaluated to determine their antiproliferative and cyto differentiating activities on HL-60 cells.

Effect of the amino versus the acylamino substituent on the product isomer distribution in the methanolysis of 5-(substituted)-2-[(methylsulfonyl)oxy]isoindole-1,3-diones

The effect of the NH2 versus the CH3CONH and PhCH2CONH substituents at the 5-position in 5-(substituted)-2-[(methylsulfonyl)oxy]isoindole-1,3-diones, on the product isomer distribution resulting from methanolysis, was investigated both experimentally and at the RHF/3-21G∗, RHF/6-31+G∗ and B3LYP/6-31+G∗ levels of theory. The influence of solvent on the transition structure was investigated using the Onsager SCRF model. The influence of these substituents on the transition state (TS) leading to tetrahedral intermediate was studied. The 5-amino (para to C-1) function makes the C-1 carbonyl carbon more electron-rich and less reactive toward nucleophilic attack. A predominance of the isomer formed from initial nucleophilic attack at C-3 is observed for the NH2 substituent, whereas this selectivity is greatly reduced for the acylamino substituents. Examination of the LUMO from ab initio calculations performed on the starting materials at the RHF/6-31G∗ level give a good qualitative description of the regioselectivity observed from experiment. Calculated ΔEa values of this initial reaction step give a qualitative description of the experimentally observed regioselectivity in agreement with the LUMO model and resonance argument.

Colour-constitution relationships in 2-acylamino-4- N,N-diethylaminoazobenzene disperse dyes

Nitration of N,N-diethylaniline in concentrated sulphuric acid afforded a readily separable mixture of the 3- and 4-nitro derivatives, the former being the major product. Reduction and subsequent reaction of 3-amino- N,N-diethylaniline with acid chlorides, chloroformates, isocyanates and sulphonylchlorides gave a range of coupling components suitable for the synthesis of blue azo disperse, using 2-bromo-4-nitro-6-cyanoaniline as diazo component. The colour of the dyes is discussed with respect to electronic and steric effects in the acylamino (and analogous) substituents; depending on the acylamino substituent, positive or negative solvatochromic effects were apparent in ethanol with respect to benzene and/or cyclohexane.

Pyrido[3,4-e]-1,2,4-triazines and related heterocycles as potential antifungal agents.

The preparation and biological activities of a series of pyrido[3,4-e]-1,2,4-triazines, 1,2,4-triazino[5,6-c]quinolines, and related fused triazines are described. Methyl, amino, and acylamino substituents were placed in the pyridyl ring of the former system. Other structural modifications included various alkyl, cycloalkyl, substituted phenyl, and heterocyclic groups in the 3-position of these ring systems. In agar dilution assays, actives in this series inhibited strains of Candida, Aspergillus, Mucor, and Trychophyton species at MIC's of less than or equal to 16 micrograms/mL.

ChemInform Abstract: Pyrido(3,4‐e)‐1,2,4‐triazines and Related Heterocycles as Potential Antifungal Agents.

The preparation and biological activities of a series of pyrido[3,4-e]-1,2,4-triazines, 1,2,4-triazino[5,6-c]quinolines, and related fused triazines are described. Methyl, amino, and acylamino substituents were placed in the pyridyl ring of the former system. Other structural modifications included various alkyl, cycloalkyl, substituted phenyl, and heterocyclic groups in the 3-position of these ring systems. In agar dilution assays, actives in this series inhibited strains of Candida, Aspergillus, Mucor, and Trychophyton species at MIC's of less than or equal to 16 micrograms/mL.

Pyrido [3,4-e]-1,2,4-triazines and related heterocycles as potential antifungal agents.

The preparation and biological activities of a series of pyrido[3,4-e]-1,2,4-triazines, 1,2,4-triazino[5,6-c]quinolines, and related fused triazines are described. Methyl, amino, and acylamino substituents were placed in the pyridyl ring of the former system. Other structural modifications included various alkyl, cycloalkyl, substituted phenyl, and heterocyclic groups in the 3-position of these ring systems. In agar dilution assays, actives in this series inhibited strains of Candida, Aspergillus, Mucor, and Trychophyton species at MIC's of less than or equal to 16 micrograms/mL.

Design of tripeptide modeled inhibitors of angiotensin-converting enzyme: Studies on the role of the N-terminal acylamino group

Several series of tripeptide modeled angiotensin-converting enzyme (ACE) inhibitors have been reported which contain an N-terminal acylamino substituent as an essential structural component for conservation of biological activity. The results of a study aimed at defining the role served by this group in enzyme/inhibitor binding by examining the consequences of systematic chemical modifications are described. The benzamido N atom is shown to play a critical function in enzyme binding of ketomethylene ACE inhibitors. Evidence is also presented to implicate the benzamido carbonyl and phenyl ring in productive enzyme binding interactions.

13C NMR spectra and three-dimensional structures of isomeric 3,4-substituted thiophans

The chemical shifts and the direct carbon-proton spin-spin coupling constants for a number of cis and trans isomers of 4-amino-substituted 3-hydroxy(acyloxy)-thiophans, the configurations of the substituents in which and the conformational states were previously established by an independent method, were studied. It was found that in the spectra of the cis isomers the signals of the vicinal 13C atoms, which bear the substituents, are shifted to strong field as compared with the trans isomers (Δδ trans-cis 1.7–4.3 ppm). Conformational γ effects of the substituents on the chemical shifts of the ring 13C atoms were noted. It is shown that a relationship exists between the direct carbon-proton spin-spin coupling constants and the spatial orientations of the acyloxy and acylamino substituents for five-membered saturated rings.

Electron impact mass spectra of 2‐[acyl(alkyl)amino]oxazoles

AbstractThe mass spectral behaviour of 2‐methyl‐N‐butyl‐N‐(4‐methyloxazol‐2‐yl)propanamide is characterized by cleavage of the acylamino substituents and the elimination of a hydroxyl radical. An understanding of this elimination has been obtained from the analysis of further 2‐[acyl(alkyl)amino]oxazoles and the use of deuterium labelled compounds.

ChemInform Abstract: ELECTROPHILIC AROMATIC REACTIVITIES VIA PYROLYSIS OF 1‐ARYLETHYL ESTERS. PART 16. THE EFFECTS OF THE ACETOXY AND ACYLAMINO SUBSTITUENTS

Chemischer InformationsdienstVolume 9, Issue 46 Preparative Organic Chemistry ChemInform Abstract: ELECTROPHILIC AROMATIC REACTIVITIES VIA PYROLYSIS OF 1-ARYLETHYL ESTERS. PART 16. THE EFFECTS OF THE ACETOXY AND ACYLAMINO SUBSTITUENTS R. TAYLOR, R. TAYLORSearch for more papers by this author R. TAYLOR, R. TAYLORSearch for more papers by this author First published: November 14, 1978 https://doi.org/10.1002/chin.197846104AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume9, Issue46November 14, 1978 RelatedInformation

Electrophilic aromatic reactivities via pyrolysis of 1-arylethyl esters. Part 16. The effects of the acetoxy and acylamino substituents

The rates of gas-phase elimination of acetic acid from the appropriate 1-arylethyl acetates have been measured to determine σ+ values for the following substitutents: p-OAc (–0.12), m-OAc (0.335), p-NHAc ( [graphic omitted] –0.62), m-NHAc (0.08). The numerical values, and the differences between them and those reported for molecular chlorination, are discussed in terms of electronic effects.

Sulfur-Free Penicillin Derivatives. V. Preparation, Hydrolysis, and Oxidative Rearrangement Of Fused Oxazoline–Azetidinones

Chlorinolysis of an anhydropenicillin affords a 2-(2′-chloro-3′S-amino, -acylamino or -phthalimido-4′-oxo)azetidinyl-3-methyl-2-butenoyl chloride, as a mixture of 2′R (cis) and 2′S (trans) epimers in which the 2′R epimer usually predominates. Hydrolysis of the acid chloride and treatment of the carboxylic acid with aqueous bicarbonate causes cyclization, in the case of a 3′-acylamino substituent, to a 2R-6-(1′-carboxy-2′-methyl-prop-1-enyl)-1-oxa-3,6-diaza-4S,5R-bicyclo[3,2,0]hept-2-ene-7-one. The mechanisms of these transformations are discussed, and alternative routes to such fused oxazoline–azetidinones are also presented.The oxazolines undergo ready hydrolysis to sulfonic acid salts of 2-(2′R-acyloxy-3′S-amino-4′-oxo)azetidinyl-3-methyl-2-butenoates upon treatment with the hydrate of a sulfonic acid in acetone solvent. Neutralization of these salts proceeds without O → N acyl transfer, because acylation yields a diacylated azetidinone in which the new acyl substituent is attached to nitrogen. Monobromination of the allylic methyl groups of these salts, followed by treatment with 2 molar-equiv. of triethylamine, leads to a deep-seated rearrangement, in high yield, to an oxazinone. The mechanism of this rearrangement and, in particular, the role of acylimines in this and related reactions, including the biosynthesis of penicillin, are discussed.