Fischer Synthesis of 1-; 5-; and 7-Substituted 3-(N-Acylamino)-2-phenylindoles

Arylhydrazones were obtained by the reaction of arylhydrazines with -(N-acylamino)acetophenones and were converted into 3-(N-acylamino)-2-phenylindoles with substituents at positions 1, 5, 6, and 7 by Fischer cyclization.     

Synthesis of the methanesulfonates of α-(4-chlorophenyl)-α-[1-(2-chlorophenyl)emenyl]-1H-1,2,4-triazole-1-ethanol and α-[1-(2-chlorophenyl)ethenyl]-α-(2,4-difluorophenyl)-1H-1,2,4-triazole-1-ethanol,alpha styryl carbinol antifungal agents

The methanesulfonates of (α-(4-chlorophenyl)-α-[1-(2-chlorophenyl)ethenyl]-1H-1,2,4-triazole-1-ethanol and α-[1-(2-chlorophenyl)ethenyl]-α-(2,4-difluorophenyl)-1H-1,2,4-triazole-1-ethanol ( 1a, b ) are orally effective α-styryl carbinol derivatives developed for the treatment and prevention of systemic fungal infections. Practical new processes amenable for the large-scale production of these compounds are described. Of note is the selection of dichlorostyrene as a convenient precursor of the styryl portion, modification of a sensitive Grignard addition into a realistic preparative reaction and the use of 1,2,4-triazole simultaneously as a base transfer agent and nucleophile.     

Acid-catalyzed reactions of 1- and 3-(α-hydroxybenzyl)indolizines

Treatment of 1-(α-hydroxybenzyl)- and 3-(α-hydroxybenzyl)indolizines with trifluoroacetic acid in dichloromethane gave phenylbis(α-indolizinyl)methanes, bis[α-(indolizinyl)benzyl] ethers and indolizines, depending upon the presence or absence of the substituent at the 2- or 5-position and the reaction conditions used.     

Synthesis and reactions with <Emphasis Type="Italic">N</Emphasis>-nucleophiles of 1-(thien-2-yl)- and 1-(4-hydroxyphenyl)-3,4,4-trichloro-3-buten-1-ones

Acylation of thiophene and phenol with 3,4,4-trichloro-3-butenoyl chloride afforded the corresponding 1-(thien-2-yl)- and 1-(4-hydroxyphenyl)-3,4,4-trichloro-3-buten-1-ones, whose reaction with amines led to the formation of 3-amino-1-(thien-2-yl, 4-hydroxyphenyl)-4,4-dichloro-2-buten-1-ones The heterocyclization of the initial ketones into pyrazole structure was not observed, and the reaction with hydrazine hydrate provided bispyrazole products, N,N′-bis(5-thien-2-yl)- and N,N′-bis[5-(4-hydroxyphenyl)-1H-pyrazol-3-ylmethylene]hydrazines.     

Syntheses of (±)-17α- and (±)-17β-hydroxytacamonine; determination of configuration at C-17

Both (±)-17α-hydroxytacamonine (3) and its 17β-isomer (4) were synthesized in two steps (one-pot) from aldehyde mixture 5/6 via the cyanohydrin reaction. NMR spectral characterization of isomer 3 revealed it to be unidentical with natural 17-hydroxytacamonine, whereas spectral data of isomer 4 were in agreement with those published for the natural isomer. The configuration at C-17 was confirmed by NOE difference spectroscopy.     

Synthesis of <Emphasis Type="Italic">N</Emphasis>-[4-hydroxy(alkoxy,acyloxy)-3-alkoxy-benzylidene]-1-(1-adamantyl)ethanamines from 1-(1-adamantyl)ethanamine hydrochloride (Rimantadine)

Reactions of 1-(1-adamantyl)ethanamine with vanillin, vanillal, veratraldehyde, 3-ethoxy-4-methoxybenzaldehyde, and 4-formyl-2-methoxy(ethoxy)phenyl esters gave previously unknown Schiff bases containing an adamantane fragment.     

Reaction of 5-(2-furyl)-1-methyl-1<Emphasis Type="Italic">H-</Emphasis> and 1-methyl-5-(2-thienyl)-1<Emphasis Type="Italic">H</Emphasis>-imidazoles with electrophilic reagents

5-(2-Furyl)-1-methyl-1H- and 1-methyl-5-(2-thienyl)-1H-imidazoles were synthesized. The electronwithdrawing effect of the 5- and 2-imidazole substituents on the furan ring was studied by ¹H NMR spectroscopy and quantum-chemical calculations. Some electrophilic substitution reactions were investigated (nitration, bromination, sulfonation, hydroxymethylation, formylation, and acylation). In some cases, depending on the reaction conditions, both the furan and thiophene ring and the imidazole fragment undergo electrophilic attack.     

5-(α-Fluorovinyl)tryptamines and 5-(α-Fluorovinyl)-3-(N-methyl-1′,2′,5′,6′,-tetrahydropyridin-3′- and -4′-yl)indoles—5-(α-Fluorovinyl)tryptamines

5-(α-Fluorovinyl)tryptamines 4a, 4b and 5-(α-fluorovinyl)-3-(N-methyl-1′,2′,5′,6′-tetrahydropyridin-3′- and -4′-yl) indoles 5a, 5b were synthesized using 5-(α-fluorovinyl)indole ( 7 ). The target compounds are bioisosteres of 5-carboxyamido substituted tryptamines and their tetrahydropyridyl analogs.     

Enzymatic kinetic resolution of 1-(3′-furyl)-3-buten-1-ol and 2-(2′-furyl)-propan-1-ol

The enzymatic kinetic resolution of the racemic alcohols 1-(3′-furyl)-3-buten-1-ol (±)-1 and 2-(2′-furyl)propan-1-ol (±)-2 was investigated by screening a range of lipases and esterases for enantioselective transacylation, as well as for enantioselective hydrolysis. For both alcohols, lipase-catalyzed hydrolysis of the derived racemic acetate gave the best results for accessing the desired (S)-enantiomers. In the case of the secondary alcohol (±)-1, ASL turned out to be the optimum enzyme, whereas PPL was found to be superior in the case of the primary alcohol (±)-2. Additionally, an alternative access to (S)-2 via Oppolzer's camphor sultam methodology is described.