Cyclic Guanidines Research Articles

New Utilizations of Optically Active Homoallylamines: Highly Stereoselective Synthesis of Cyclic Guanidine and Thiourea

Halocyclizations of optically active homoallylguanidine and homoallylthiourea were examined. These reactions proceeded stereoselectively to give six membered cyclic guanidines and thiourea. High 1,3-asymmetric induction by the homoallylic substituents is observed in these halocyclizations.

A Fast and Parallel Route to Cyclic Isothioureas and Guanidines with Use of Microwave‐Assisted Chemistry.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A Fast and Parallel Route to Cyclic Isothioureas and Guanidines with Use of Microwave‐Assisted Chemistry.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A fast and parallel route to cyclic isothioureas and guanidines with use of microwave-assisted chemistry.

A fast and simple approach to novel cyclic isothioureas and related guanidine derivatives is presented in this study. The construction of the central basic scaffolds is achieved solely by the application of microwave-assisted chemistry, without any need of activating agents or protecting group manipulations. The product formation of various substituted guanidines from the corresponding isothiouronium salts was controlled by the nucleophilicity of the counterion and influenced by the reaction temperature. Further, a new fast-track access to tetrahydropyrimidin-2-ylamines was developed.

1,8-bis(dimethylethyleneguanidino)naphthalene: tailoring the basicity of bisguanidine "proton sponges" by experiment and theory.

1,8-bis(dimethylethyleneguanidino)naphthalene (DMEGN), the second example of a peralkyl guanidine "proton sponge" based on the 1,8-naphthalene backbone, was prepared and fully characterized. The crystal structure analysis of monoprotonated DMEGN reveals an unsymmetrical intramolecular hydrogen bridge. A decrease in the basicity with respect to the noncyclic parent 1,8-bis(tetramethylguanidino)naphthalene was found. Nevertheless, a new proton sponge provides a new crossbar in the ladder of highly basic neutral organic compounds. A detailed theoretical study of DMEGN and related cyclic guanidines explains this surprising experimental result. Homodesmotic reactions reveal that the intramolecular hydrogen bond contributes effectively 10 kcal/mol to proton affinity of DMEGN.

Intramolecular Guanidine Epoxide Ring Opening Reactions.

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Enantiopure Guanidine Bases for Enantioselective Enone Epoxidations. Part 2. Cyclic Guanidines.

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Intramolecular guanidine epoxide ring opening reactions

The synthesis of a range of cyclic guanidines via intramolecular ring opening of epoxides or iodocyclisation is reported. A preliminary investigation of the glycosidase inhibitory activity of these substances is also discussed.

A Versatile Synthesis of 2‐Amino‐4H‐pyrido[1,2‐a][1,3,5]triazin‐4‐ones from 2‐Aminopyridines.

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Enantiopure Guanidine Bases for Enantioselective Enone Epoxidations: 2, Cyclic Guanidines

A range of structurally and functionally varied enantiopure cyclic and bicyclic guanidines has been prepared and evaluated in the enantioselective epoxidation of 3-tert-butoxycarbonylamino-4,4-dimethoxycyclohexa-2,5-dien-1-one 1 using tert-butylhydroperoxide. Encouraging enantiomeric excesses were observed (up to 60%). Low enantiomeric excesses were also observed with 2-methylnaphthoquinone and trans-chalcone.

Enantiopure Guanidine Bases For Enantioselective Enone Epoxidations: 1, Acyclic Guanidines

A range of structurally and functionally varied enantiopure cyclic and bicyclic guanidines has been prepared and evaluated in the enantioselective epoxidation of 3-tert-butoxycarbonylamino-4,4-dimethoxycyclohexa-2,5-dien-1-one 1 using tert-butylhydroperoxide. Encouraging enantiomeric excesses were observed (up to 60%). Low enantiomeric excesses were also observed with 2-methylnaphthoquinone and trans-chalcone.

A versatile synthesis of 2‐amino‐4H‐pyrido[1,2‐a][1,3,5]triazin‐4‐ones from 2‐aminopyridines

AbstractThe quasi‐one pot synthesis of new 2‐aminopyrido[1,2‐a][1,3,5]triazin‐4‐ones starting from 2‐amino‐pyridine and 2‐aminopicolines is herein described in order to obtain a library of cyclic guanidines.

A novel approach for the solid-phase synthesis of substituted cyclic guanidines, their respective bis analogues, and N-acylated guanidines from N-acylated amino acid amides.

An efficient method for the solid-phase synthesis of cyclic guanidines from N-acylated amino acid amides, bis cyclic guanidines from N-acylated dipeptides derived from orthogonally protected diamino acids, and N-acylated guanidines from disubstituted cyclic guanidines is described. The exhaustive reduction of N-acylated amino acid amides yields diamines that on treatment with cyanogen bromide lead to the formation of cyclic guanidines. Resin-bound orthogonally protected diamino acids (i.e., N(alpha)-Fmoc-N(x)-(Boc)-diamino acid, x = beta, gamma, delta, epsilon) were N-acylated following removal of the Fmoc group. Removal of the Boc functionality from the side chain then generated a primary amine. Subsequent coupling of Boc amino acids, followed by removal of the Boc group, generated dipeptides that were N-acylated. Exhaustive reduction of amide bonds of the N-acylated dipeptides generated tetraamines having four secondary amines, which upon cyclization with cyanogen bromide afforded the resin-bound trisubstituted bis cyclic guanidines. Treatment of the resin-bound disubstituted cyclic guanidines with carboxylic acids gave N-acylated guanidines. On the basis of their high yield and purity, bis cyclic guanidines derived from N(alpha)-Fmoc-N(epsilon)-Boc-lysine and N-acylated guanidines were chosen for preparation of mixture-based combinatorial libraries. Details of the preparation of these positional scanning libraries using the "libraries from libraries" concept are presented.

Synthesis of 2-substituted polyhydroxytetrahydropyrimidines (N-hydroxy cyclic guanidino-sugars): transition-state mimics of enzymatic glycosidic cleavage.

The synthesis of 2'-substituted polyhydroxytetrahydropyrimidines as transition-state mimics of enzymatic glycosidic cleavage has been achieved by using guanylation and cyclization methodologies. The D-galacto type N-hydroxy cyclic guanidino-sugar 21 was synthesized in six steps from amine 7 and thiourea 14 in an overall yield of 59%. To further derivatize compound 21 to incorporate the leaving group moiety, we have synthesized 2-methylsulfanyl compounds 26-29 as key intermediates. The 2-methylsulfanyl group in 29 was displaced with amines, assisted by silver tetrafluoroborate as Lewis acid, to give protected cyclic guanidines 30-32 in moderate yields (60-67%). Removal of the protecting groups in 32 gave the D-galacto-type N-hydroxy cyclic guanidino-sugar 34. The key steps in the synthesis of the 6-deoxy-DL-galacto type N-hydroxy cyclic guanidino-sugars 49, 54, and 64-66 involve cyclization of the appropriate acetal intermediates (45, 50, and 58-60) followed by removal of the protecting groups.

Introduction of cyclic guanidines into cationic lipids for non-viral gene delivery

In order to study the impact of chemical modifications of lipopolyamines on their gene delivery properties, we have introduced cyclic guanidines into the polyamine moiety. These lipopolyamino-cycloguanidines can be easily obtained by reacting polyamines with 2-methylmercapto-2-imidazolinium iodide or 2-methylmercapto tetrahydropyrimidinium iodide. These lipopolyamino-cycloguanidines constitute a novel family of cationic lipids.

Solution Parallel Synthesis of Cyclic Guanidines

Solution Parallel Synthesis of Cyclic Guanidines

Cyclic guanidines. Part 6.1 Synthesis of benzimidazoles by intramolecular vicarious nucleophilic substitution of hydrogen

m-Nitrophenylguanidines, which carry a vicarious leaving group, cyclize under basic conditions yielding nitrobenzimidazoles. Preliminary observations of the regioselectivity of the ring closure reaction are reported.

Saturated heterocycles. 242. Synthesis of 2‐substituted‐6‐(6′,7′‐dimethoxy‐3′,4′‐dihydro‐1′‐isoquinolyl)‐5,6,7,8‐tetrahydro‐ quinazolin‐4(3H)‐one Derivatives

AbstractIn the reactions of the recently synthesized β‐ketoesters 1‐[(3′‐methoxycarbonyl‐ and 1‐[(3′‐ethoxycarbonyl‐4′‐oxo)‐1′‐cyclohexyl]‐3,4‐dihydroisoquinoline 4, 5 with amidines or cyclic guanidines, a number of 2‐substituted‐6‐(6′,7′‐dimethoxy‐3′,4′‐dihydro‐1′‐isoquinolyl)‐5,6,7,8‐tetrahydroquinazolin‐4(3H)‐one derivatives 6–8 were prepared. The new compounds possess various pharmacological actions.

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.