Syntheses of apogalanthamine analogs as α-adrenergic blocking agents. IX. Syntheses of optically active 8-hydroxy-6-methyl-5,6,7,8-tetrahydrodibenz[c,e]azocines

(8R) and (8S)-Hydroxy-6-methyl-5,6,7,8-tetrahydrodibenz[c,e]azocines (R- and S- 1 ) were synthesized by oxidative kinetic resolution of N-(2-iodobenzyl)-β-(2-iodophenyl)ethanolamine ( 8 ), followed by cyclization of the optically active acetates (R- and S- 6 ) of R- and S- 8 with zero-valent nickel to (8R)- and (8S)-acetoxyazocines (R- and S- 7 ), and by hydrolysis of the acetates ( R - and S- 7 ).     

Suzuki-Miyaura and Stille reactions as key steps in the synthesis of diversely functionalized Amaryllidaceae alkaloid analogs bearing a 5,6,7,8-tetrahydrobenzo[c,e]azocine skeleton

Microwave-assisted Suzuki-Miyaura and Stille cross-coupling reactions for the synthesis of highly electron-rich and diversely functionalized biaryl intermediates are presented. Microwave-irradiation has been demonstrated to be a very powerful tool for performing difficult transition metal-catalyzed cross-coupling reactions with unfavorably substituted coupling partners. The key biaryl intermediates were used for the microwave-enhanced construction of the 5,6,7,8-tetrahydrobenzo[c,e]azocine skeleton of the Apogalanthamine analogs. The success of the strategy is demonstrated by synthesizing a number of hitherto unknown, diversely functionalized, natural product analogs.     

Syntheses based on dimethylpyrazoles. 9. Synthesis and spectral peculiarities of isomeric pyrazolo[3′,4′-5,6]- and-[5′,4′-5,6]-pyrimido[1,2-b]benzo[d,e]isoquinoline-4,12-diones

2-Methyl-2,4,12,13H-pyrazolo[3,4-5,6]pyrimido[1,2-b]benzo[d,e]isoquinoline-4,12-dione and its 8-nitro- and 8-amino-substituted derivatives were obtained starting from 4-amino-3-carbamoyl-1-methylpyrazole and naphthalic and 4-nitronaphthalic anhydrides. The spectral properties of the synthesized compounds were studied.See [1] for Communication 8.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 237–241, February, 1990.     

Synthetic Amebicides. VIII. 7,7′-[Iminobis(alkyleneimino) [bis[benz[c] acridines] and Congeneric 9-Aminoacridines, 12-Aminobenz[a] acridines, [2-Aminobenz[b] acridines,and 4-Aminoquinolines

Thirty-five 7,7′-(iminodialkylenediimino))bis[benz[c]acridines] (VII), 7,7′-(alkylene- and phenylenediimino)bis[benz[c]acridines] (VIII and IXa-c), [iminobis(alkyleneimino)]bis[acridines, benz[a]acridines, benz[b]acridines, and quinolines] (X, Xla-c, XII, XIII, and XIVa-c), and [alkylenebis(iminoalkyleneimino)]bis[acridines, benz[c]acridines, and quinolincs] (XVI, XVII, XVIIIa and b, and XIXa-c) were synthesized by the condensation of one equivalent of the appropriate alkylenediamine with two equivalents of the requisite chloroheterocycle in phenol. Many of the bis(aminoheterocyclic) compounds are highly active against Entamoeba histolytica in vitro and in experimental animals.     

Electrophilic substitution in a series of derivatives of 5,6,7,8-tetrahydro-2a,4a-diazacyclopenta[c,d]azulene

Protonation, acylation, nitrosation, and addition of iso(thio)cyanates occur readily at position two of 1,4-diaryl-5,6,7,8-tetrahydro-2a,4a-diazacyclopenta[c,d]azulenes.T. G. Shevchenko Chernigov Pedagogical Institute, Chernigov 250038. Taras Shevchenko Kiev University, Kiev 252017. Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 904–908, July, 1997.     

Novel polycyclic heterocycles. VIII. 6,11-dihydro-12H-dibenzo[b,f] [1,4]thiazocines and their derivatives

6,11-Dihydro-12H-dibenzo[b,f][1,4]thiazocine, 4 , and its 2-chloro, 7 , and 2-(trifluoromethyl)-, 1 , derivatives, were prepared by the reaction of an o-aminobenzenethiol and α,α-dibromo-o-xylene. Acylation and alkylation at position-12 gave a series of ω-haloacyl-, ω-amino-acyl, and ω-aminoalkyl derivatives of these heterocycles. The conformations, proton magnetic resonance spectra, and x-ray crystallographic studies of these compounds are discussed.     

Synthesis and biological activity of 11-[4-(cinnamyl)-1-piperazinyl]- 6,11-dihydrodibenz[b,e]oxepin derivatives, potential agents for the treatment of cerebrovascular disorders.

A series of 11-[4-(cinnamyl)-1-piperazinyl]-6,11-dihydrodibenz[b,e] oxepins and related compounds were synthesized and evaluated for their protective activities against complete ischemia, normobaric hypoxia, lipidperoxidation and convulsion. Structure-activity relationship studies of this series led to the finding of (E)-1-(3-fluoro-6,11-dihydrodibenz[b,e]oxepin-11-yl)-4-(3- phenyl-2-propenyl)piperazine dimaleate (50), AJ-3941 with the most appropriate property for combined pharmacological activities. Compound 50 also shows an inhibitory effect against cerebral edema as well when orally given to rats.     

Syntheses of an isoannelated annulene,a bisdehydro[14]annuleno[c]furan and bisdehydro[14]annulene derivatives

A bisdehydro[14]annuleno[c]furan, an isoannelated diatropic annulene, has been synthesized. Cyclic glycol, a precursor of the annuleno[c]furan, could be converted into bisdehydro[14]annulene derivatives under mild acidic conditions.     

3-[2(4)-Pyrimidinyl]coumarins and their condensed analogs

3-Pyrimidinylcoumarins have been synthesized by interacting 2- and 4-pyrimidinylacetonitriles with substituted salicylic aldehydes, but 9-pyrimidinylpyrano[2,3-f]chromene-4,8-diones were obtained with 8-formyl-7-hydroxychromones. Modification of the corresponding 7-hydroxycoumarins was carried out by acylation and aminomethylation.     

Quino[1,2-c]quinazolines. I. Synthesis of quino[1,2-c]quinazolinium derivatives and the related indazolo[2,3-a]quinoline derivatives as analogs of the antitumor benzo[c]phenanthridine alkaloids

9,10-Dimethoxy-1,2,3,4,12,13-hexahydro-1-oxoquino[1,2-c]quinazolinium perchlorate, 1,2,3,4,13,24-hexahydro-1-oxo[1,3]dioxolo[4,5-g]quino[1,2-c]quinazolinium perchlorate, 6-methyl-2,3,9,10-tetramethoxyquino-[1,2-c]quinazolinium perchlorate and 2,3-dimethoxy-13-methyl[1,3]dioxolo[4′,5′:6,7]quino[1,2-c]quinazolinium perchlorate were synthesized as analogs of the potent antitumor benzo[c]phenanthridine alkaloids nitidine and fagaronine. The related 2,3,8,9-tetramethoxyindazolo[2,3-a]quinoline and 2,3-dimethoxy[1,3]dioxolo-[4,5-g]indazolo[2,3-a]quinoline were also synthesized. Further, the novel formation of 6,7-dimethoxy-2-(2-ethylamino-4,5-dimethoxyphenyl)quinoline via reductive alkylation with Raney nickel in refluxing ethanol is also reported.