Synthesis of fused bicyclic glutarimides

We describe an efficient route towards the synthesis of fused bicyclic glutarimides using facile [3+3] reaction of α-sulfonylacetamides with different α,β-unsaturated esters as the key step. Intramolecular cyclization of 4-substituted 3-sulfonylglutarimide to form 5,6-, 6,6- or 6,7-fused bicyclic glutarimides was accomplished via alkylation, oxidative cyclization or ring-closing metathesis in modest yield.     

Synthesis of saturated bicyclic diesters

Bicyclic saturated diesters were synthesized by the catalytic addition of monobasic saturated acids to unsaturated bicyclic esters. A possible mechanism of the reaction was proposed.     

Synthesis of bicyclic tertiary alpha-amino acids

Novel bicyclic alpha-amino acids, exo and endo-1-azabicyclo[2.2.1]heptane-2-carboxylic acid, 1-azabicyclo[2.2.1]heptane-7-carboxylic acid, and 1-azabicyclo[3.2.2]nonane-2-carboxylic acid have been readily synthesized for the generation of neuronal nicotinic receptor ligands. Alkylation of glycine-derived Schiff bases or nitroacetates with cyclic ether electrophiles, followed by acid-induced ring opening and cyclization in NH4OH, allowed for the preparation of substantial quantities of the three tertiary bicyclic alpha-amino acids.     

Synthesis of bicyclic analogues of deoxyvasicinone

6-Methyl-2,3-tri-, -tetra-, and -pentamethylene-3,4-dihydropyrimidin-4-ones and 6-phenyl-2,3-tri-3,4-dihydropyrimidin-4-one (bicyclic analogues of deoxyvasicinone) have been synthesized by the condensation of ethyl esters of -aminocrotonic and -aminocinnamic acids with lactams. It has been shown that the occurrence of the reaction and yields of the products of the condensation of ethyl -aminocrotonate with lactams depend both on the number of methylene groups in the lactams and also on the reaction conditions. With an increase in the number of methylene groups of the lactams the yields of condensation products decrease.Institute of Chemistry of Plant Substances, Academy of Sciences of the Uzbek SSR, Tashkent. A. Navoi Samarkand State University. Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 394–396, May–June, 1991.     

Synthesis of a bicyclic double-headed nucleoside

An attempt of preparing a carbocyclic LNA-analogue using different RCM-methods failed. However, a compound with a hemiacetal linker between the C2′ and the C4′-positions was isolated and found to be a suitable substrate for making a conformationally restricted double-headed nucleoside. This contains two uracil nucleobases organized on a bicyclic skeleton and is locked in an N-type conformation.     

Synthesis of novel bicyclic pyridazine nucleosides

The synthesis of some [6:6]- or [6:5]-fused bicyclic pyridazin-6-one nucleosides, starting from 4,5-dichloro-3-nitro(or amino) and 3-hydrazinopyridazin-6-one nucleosides is described.     

Synthesis of bicyclic quinones via 1,4-diacetoxyanthracene

1,4-Diacetoxyanthracene is introduced as a convenient intermediate for the syntheses of bicyclic quinones and diquinones.     

Synthesis of the bicyclic core of tagetitoxin

A synthesis of the 9-oxa-3-thiabicyclo[3.3.1]nonane ring system, which constitutes the core of the RNA polymerase inhibitor tagetitoxin, has been achieved through cyclisation of a thiol onto an electrophilic ketone.     

Synthesis of some new bicyclic pyrazoline derivatives

2,6-Diarylidenecyclohexanones react with hydrazine to give the corresponding bicyclic pyrazolines. The synthesis of a series of twenty eight substituted pyrazolines is described. The structure of all products was confirmed by microanalyses, ir and nmr data.     

Synthesis of bicyclic pyrimidine derivatives as ATP analogues

A highly efficient and general solid-phase synthesis of bicyclic pyrimidine derivatives that target purine dependent proteins is reported. The synthesis of the key intermediate, 4,6-disubstituted-5-amino-pyrimidine, involved reduction of the corresponding nitro derivatives using 1,1'-dioctyl-viologen in a triphasic milieu. The mild reduction conditions enable the use of any acid labile solid support as well as a wide range of combinatorial substituents, thus enabling the synthesis of large libraries of highly diverse bicyclic pyrimidines. Alternative reduction conditions with tin(II) chloride and structure-reactivity studies are discussed as well.     

Synthesis of highly functionalized strained bicyclic dilactam derivatives

An efficient and modest protocol has been utilized for the synthesis of bicyclic dilactam derivatives through one-pot multicomponent domino reaction starting from various cyclic ketones under mild condition. The synthesized motif shows four stereogenic centers with two quaternary amine functionalities and such molecular arrangements are very fascinating and rare to obtain. We propose a mechanism for the formation of bicyclic dilactams through aldol condensation/condensation of cyanoacetamides/cyclization of condensed intermediate.     

Synthesis of fused bicyclic imidazoles by ring-closing metathesis

The preparation of a number of dienylimidazole via chemoselective metal-halogen exchange and their utility in ring-closing metathesis is described. Essentially all regioisomeric permutations participate in metathesis with the notable exception of 4-vinyl-5-allylimidazoles, provided that the imidazole N3 atom is protonated.     

Synthesis of new potentially bioactive bicyclic 2-pyridones

Three convenient methods of reduction of the nitro group of 5-nitroimidazoles and 5-nitrothiazole that bear a diethylmethylene malonate group in an ortho-like position with respect to the nitro group and cyclization of the resulting amino derivatives are reported. These reactions afforded the target bicyclic 2-pyridones in good to excellent yields.     

Synthesis of bicyclic diesters of malonic and succinic acids

Monoesters of malonic and succinic acids have been prepared in high yields by the BF₃·OEt₂-catalyzed addition of the acids to bicyclo[2.2.1]hept-2-ene. The synthesized monoesters were introduced in the reaction of esterification with saturated monoatomic alcohols С₂–С₇ in the presence of the KU-2-8 catalyst in the H-form, and the corresponding mixed diesters of dicarboxylic acids were obtained in high yields.     

Synthesis of bicyclic and allyl diesters of oxalic acid

An effective synthesis of mixed, bicyclic, and allyl diesters of oxalic acid. The procedure involves addition of oxalic acid to bicycloheptene hydrocarbons followed by esterification of the resulting monoesters with allyl alcohol. The synthesized diesters are new reactive monomers for the synthesis of high-molecular and other organic compounds.     

Synthesis and structural features of cyclobutane-containing chiral bicyclic ureas

Efficient and stereoselective synthetic routes have been developed for the preparation of chiral N-monoprotected cyclobutane bicyclic ureas in which one of the NH groups is protected as a benzyl or tert-butyl carbamate. Ureas in both enantiomeric forms were obtained from a common chiral precursor via the selective manipulation of functional groups. These compounds have been subjected to a structural study in solution and in the solid state. NMR, IR and TEM techniques evidence a strong tendency to aggregation in solution giving regular assemblies, which is a result of intermolecular urea N–H?OC hydrogen bonding. In the solid state, X-ray analysis shows that two urea molecules interact through only one hydrogen bond yielding infinite chains. This fact and the almost complete coplanarity of both the urea and the carbamate carbonyl groups determine the crystal packing to be formed by a parallel molecular arrangement. All these structural features are well supported by theoretical calculations that allow us to conclude that the formation of a network based on hydrogen bonding is energetically favourable.     

Synthesis and rotatory dispersion of cisoid bicyclic enamino ketones

Optically active cisoid, bicyclic, enamino ketones — N-(-phenylethyl)-4-keto-^9,10-octa-hydroquinoline and N-(-phenylethyl)-4-keto-^8,9-hexahydropyridine — were synthesized by the condensation of ethyl -[N-(-phenylethyl)amino]propionate with cyclohexanone and cyclopentanone, while ethyl -(N-benzylamino)propionate and cyclohexanone gave N-benzyl-4-keto-^9,10-octahydroquinoline. A study of the rotatory dispersion of the compounds obtained demonstrated that a strong positive Cotton effect at 330–350 nm, which is associated with the presence of a cis-enamino ketone chromophore, is characteristic for them.Communication XXVIII of the series Stereochemical Investigations. See [1] for communication XXVII.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 541–545, April, 1972.     

Synthesis of sterically congested bicyclic tetrahydrofurans via Pd-catalyzed cyclization

Prins-type cyclization followed by palladium-catalyzed cyclization provided sterically congested bi- or tricyclic tetrahydrofurans, which are very stereoselective as well. cis-2,5-Disubstituted tetrahydrofurans obtained from Prins-type cyclization have an allenyl group and a functional group such as alcohol, carboxylic acid, and aryl halide. The tetrahydrofurans bearing an allene group underwent palladium-catalyzed cyclization to give sterically congested bi- or tricyclic tetrahydrofurans.