Acyclic Guanidines Research Articles

A DFT Investigation of the Reactivity of Guanidinium Salts in Tandem aza-Michael Addition/Intramolecular Cyclization

A proposed mechanism of the reaction of guanidinium chlorides with dimethyl acetylenedicarboxylate in a tandem aza-Michael addition reaction/intramolecular cyclization was investigated by DFT M06-2X and B3LYP computational approaches. The energies of the products were compared against the G3, M08-HX, M11, and wB97xD data or experimentally obtained product ratios. The structural diversity of the products was interpreted by the concurrent formation of different tautomers formed in situ upon deprotonation with a 2-chlorofumarate anion. A comparison of relative energies of the characteristic stationary points along the examined reaction paths indicated that the initial nucleophilic addition is energetically the most demanding process. The overall reaction is strongly exergonic, as predicted by both methods, which is primarily due to methanol elimination during the intramolecular cyclization step producing cyclic amide structures. Formation of a five-membered ring upon intramolecular cyclization is highly favored for the acyclic guanidine, while optimal product structure for the cyclic guanidines is based on a 1,5,7-triaza [4.3.0]-bicyclononane skeleton. Relative stabilities of the possible products calculated by the employed DFT methods were compared against the experimental product ratio. The best agreement was obtained for the M08-HX approach while the B3LYP approach provided somewhat better results than the M06-2X and M11 methods.

Silver acetate-catalyzed synthesis of cyclic sulfonyl guanidine with exocyclic double bond

An efficient protocol for the synthesis of cyclic guanidine with exocyclic double bond has been developed. The synthesis has been achieved via intramolecular hydroamination of an intermediate propargyl guanidine by using silver acetate as catalyst in the presence of acetic acid. The reaction proceeds via the formation of acyclic propargyl guanidine in a one-pot reaction of N,N-dibromoarylsulfonamides, isonitriles, and propargylamine in the presence of K2CO3. In the second stage of the synthesis, the acyclic guanidine selectively undergoes 5-exo-dig cyclization in the presence of silver acetate and acetic acid to produce the five-membered cyclic guanidine framework having an exocyclic double bond as the constituent part. Short reaction time, wide substrate scope with good to high yields, and good functional group tolerance are the remarkable achievement of the present protocol.

Asymmetric Sonogashira C(sp3)–C(sp) bond coupling enabled by a copper(i) complex of a new guanidine-hybrid ligand

A type of new chiral nitrogen-donor hybrid ligand bearing acyclic guanidine, amide, and pyridine subunits was rationalized for Cu(i)-catalyzed asymmetric Sonogashira C(sp3)–C(sp) cross-coupling.

Unguiculin A and Ptilomycalins E-H, Antimalarial Guanidine Alkaloids from the Marine Sponge Monanchora unguiculata.

Chemical study of the CH2Cl2-MeOH (1:1) extract from the sponge Monanchora unguiculata collected in Madagascar highlighted five new compounds, one acyclic guanidine alkaloid, unguiculin A (1) and four pentacyclic alkaloids, ptilomycalins E-H (2-5), along with four known compounds: crambescidin 800 (6) and crambescidin 359 (7), crambescidic acid (8), and fromiamycalin (9). Their structures were elucidated by 1D and 2D NMR spectra and HRESIMS data. All compounds were evaluated for their cytotoxicity against KB cells and their antiplasmodial activity. The new ptilomycalin E (2) and the mixture of the new ptilomycalins G (4) and H (5) showed promising cytotoxicity against KB cells with IC50 values of 0.85 and 0.92 μM, respectively. Ptilomycalin F (3) and fromiamycalin (9) exhibited promising activity against Plasmodium falciparum with IC50 values of 0.23 and 0.24 μM, respectively.

ChemInform Abstract: Ionic Liquids Derived from Organosuperbases: En Route to Superionic Liquids

AbstractReview: 141 refs.

Electronic Activity Tuning of Acyclic Guanidines for Lactide Polymerization

Novel aromatic guanidine-based organocatalysts for the ring-opening of l-lactide were synthesized and applied in comprehensive polymerization experiments and kinetic studies. The introduction of el...

New Derivatives of Natural Acyclic Guanidine Alkaloids with TRPV Receptor-Regulating Properties

The guanidine alkaloids, dihydropulchranin A (2), prepared from pulchranin A from the sponge Monanchora pulchra, and hexadecylguanidine (3), a synthetic analog of pulchranins, were studied for their TRPV channel-regulating activities. Compound 2 was active as an inhibitor of rTRPV1 and hTRPV3 receptors with EC50 values of 24.3 and 59.1 μM, respectively. Hexadecylguanidine (3) was not active against these receptors.

ChemInform Abstract: Convenient Synthesis of Acyclic Guanidines from Isothiouronium Iodides and Amines Without Protection of the Amino Groups.

Acyclic guanidines were obtained in one step by reaction of isothiouronium iodides with an equimolar amount of various amines in tetrahydrofuran. The reactions proceeded under ambient conditions without N-protection/deprotection to afford the corresponding substituted guanidines in quantitative yields.

Convenient Synthesis of Acyclic Guanidines from Isothiouronium Iodides and Amines without Protection of the Amino Groups

Acyclic guanidines were obtained in one step by reaction of isothiouronium iodides with an equimolar amount of various amines in tetrahydrofuran. The reactions proceeded under ambient conditions without N-protection/deprotection to afford the corresponding substituted guanidines in quantitative yields.

Pulchranins B and C, New Acyclic Guanidine Alkaloids from the Far-Eastern Marine Sponge Monanchora Pulchra

New marine natural products, pulchranins B and C (2 and 3), were isolated from the marine sponge Monanchora pulchra and their structures were established using NMR and MS analysis. Compounds 2 and 3 were moderately active as inhibitors of TRPV1 (EC50 value of 95 and 183 microM, respectively) and less potent against TRPV3 and TRPA1 receptors.

Is the Isodesmic Reaction Approach a Better Model for Accurate Calculation of pK a of Organic Superbases? A Computational Study

The acid-base dissociation constant (p<i>K</i> _a) can be related to the solubility and binding of drugs. However, measuring accurate p<i>K</i> _a values is a challenging task. In this study, we have examined the p<i>K</i> _a of various organic superbases: naphthalenes, cyclic guanidines, vinamidines, and acyclic guanidines computationally. We have calculated the p<i>K</i> _a of such superbases by employing two methods: a conventional thermodynamic cycle and a second method based on an isodesmic reaction. The thermodynamic cycle involves computation of solvation free energy by using gas-phase free energy and the difference in solvation free energies (∆G_solv) between products and reactants. Calculations performed with the isodesmic reaction approach do not use the free energy of solvation; hence, the accuracy of the approach is less sensitive to solvent molecules and global charges of the calculated species. The root-mean-square errors (RMSE) predict that the p<i>K</i> _a of the studied organic superbases are more accurate when calculated with the isodesmic reaction approach.

Acyclic Guanidines as Organic Catalysts for Living Polymerization of Lactide

We describe a facile route to structurally diverse guanidinium organic catalysts by reaction of carbodiimides with secondary amines. The efficacy of these catalysts for the living ring-opening polymerization (ROP) of lactide was demonstrated including predictable molecular weights and end-group fidelity. Theoretical studies indicate that the acyclic guanidines are less basic than 1,5,7-triazabicyclo[4.4.0]dec-5-ene (TBD), but as for the more active TBD, they catalyze ring opening by activation of the alcohol and by stabilizing the resultant tetrahedral intermediates through hydrogen bonding. These results demonstrate that weak secondary interactions are an important concept for controlled polymerization.

Canarosine: A new guanidine alkaloid from Canavalia rosea with inhibitory activity on dopamine D1 receptors

A new acyclic guanidine alkaloid, canarosine (1), together with five known compounds, β-sitosterol (2), stigmasterol (3), daucosterol (4), epi-inositol 6-O-methyl ether (5), and rutin (6), were isolated from the aerial parts of Canavalia rosea. Their structures were established on the basis of their spectroscopic data. In the radioligand receptor binding assay, canarosine (1), at a concentration of 100 μg/ml, caused 91% inhibition of the dopamine D1 receptor binding with an IC50 value of 39.4 ± 5.8 μM.

Mechanisms of action of insecticides on ligand-gated ion channels

Ligand-gated ion channels (LGICs) mediate fast synaptic neurotransmission and are important targets for insecticides. Thus, the actions of several insecticides have been explored in electrophysiological studies on recombinant and native insect neuronal LGICs. I have shown that non-competitive antagonists of γ-aminobutyric acid gated Cl− channels also act on glutamate-gated Cl− channels, albeit at higher concentrations. Neonicotinoids are more potent agonists on recombinant hybrid nicotinic acetylcholine receptors (nAChRs) consisting of Drosophila Dα2 and vertebrate β2 subunits than those consisting of only vertebrate nAChR subunits (α4β2). Using this hybrid nAChR, clothianidin and related compounds containing a acyclic guanidine moiety were found to be super-agonists. Similar super-agonist actions of neonicotinoids were also observed on cultured Drosophila cholinergic neurons. Single channel nAChR recordings show that a clothianidin analogue induces a high conductance state in channel opening more frequently than acetylcholine, thereby offering a possible explanation for its super-agonist action. Unlike the case for clothianidin, imidacloprid attenuates the acetylcholine-induced re-sponse of native neuronal nAChRs when co-applied with ACh. These new discoveries add to our understanding of both the selectivity and the diverse actions of insecticides targeting LGICs.

Actions of imidacloprid, clothianidin and related neonicotinoids on nicotinic acetylcholine receptors of American cockroach neurons and their relationships with insecticidal potency

The actions of neonicotinoid insecticides on nicotinic acetylcholine receptors (nAChRs) in the terminal abdominal ganglion neurons of the American cockroach were investigated using whole-cell patch-clamp electrophysiology. Neonicotinoids possessing a nitromethylene group showed higher agonist affinity than the corresponding nitroimine analogues, whereas compounds with an acyclic guanidine moiety showed greater agonist efficacy than the corresponding cyclic compounds. Imidacloprid showed the lowest agonist efficacy of all neonicotinoids and low concentrations of imidacloprid attenuated acetylcholine-induced currents. However, such blocking actions were minimal with other neonicotinoids. The diverse actions of neonicotinoids on nAChRs, combined with target accessibility based on hydrophobicity, appears to account for their insecticidal potency on cockroaches measured in the presence of metabolic inhibitors. © Pesticide Science Society of Japan

A Practical Synthesis of Highly Functionalized Fused 1,6-Dihydroimidazo-[1,2-a]imidazole-2,5-diones, Key Intermediates for LFA-1 Inhibitors

Correction to: A Practical Synthesis of Highly Functionalized Fused 1,6-Dihydroimidazo-[1,2-a]imidazole-2,5-diones, Key Intermediates for LFA-1 InhibitorsSynlett 2004; 2004(15): 2800-2802DOI: 10.1055/s-2004-835638

Enantiopure Guanidine Bases for Enantioselective Enone Epoxidations. Part 1. Acyclic Guanidines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Alkylguanidines as catalysts for the transesterification of rapeseed oil

The transesterification of rapeseed oil with methanol has been studied in the presence of eight substituted cyclic and acyclic guanidines and compared with unsubstituted guanidine. The catalytic activity of the guanidines depends mainly on their intrinsic base strength. With a long alkyl chain on the guanidine, no lipophilic effect is observed. The best catalyst found is commercial 1,5,7-triazabicyclo[4.4.0] dec-5-ene which, when used at 1 mol%, produces a 90% yield of methyl esters with 1 h of reaction time.

Superbases in the gas phase. Part II. Further extension of the basicity scale using acyclic and cyclic guanidines

AbstractThe superbase gas‐phase scale has been further extended up to proton affinities of ca 1080 kJ mol−1 by use of cyclic and acyclic guanidines and vinamidines. Structural features such as Y‐conjugation, vinylogy and intramolecular ionic hydrogen bonding leading to their superbasic behaviour are analysed. Solvation effects by water and acetonitrile on basicity are discussed. From a correlation pKa(acetonitrile) vs gas‐phase basicity, proton affinity values in the range 1070–1410 kJ mol−1 are predicted for Schwesinger phosphazene compounds.