The Structure and Function of Oestrogens. II. The Synthesis and Oestrogenic Activity of 4b-Methyl 4b,5,6,12-tetrahydrochrysene-2,8-diol and 4b-Methyl-cis-4b,5,6,10b,11,12-hexahydrochrysene-2,8-diol and Related Compounds

1979 ◽  
Vol 32 (5) ◽  
pp. 1107 ◽  
Author(s):  
DJ Collins ◽  
WA Matthews ◽  
GM Stone
Keyword(s):  
Hydrogen Peroxide ◽  
Structure And Function ◽  
Lithium Aluminium Hydride ◽  
Alkaline Hydrogen Peroxide ◽  
Lithium Aluminium ◽  
Methylmagnesium Iodide ◽  
And Function ◽  
Dihydroxy Compound ◽  
Related Compounds

Hydroboration of an inseparable mixture of 2,8-dimethoxy-5,6-dihydrochrysene (5a) and 2,8-dimethoxy-4b-methyl-4b,5,6,12-tetrahydrochrysene (6a) followed by oxidation with alkaline hydrogen peroxide gave a mixture of (4bα,10bβ,11β)-2,8-dimethoxy-4b-methyl-4b,5,6,10a,11,12-hexahydrochrysen-11-ol (10a) and its (4bβ,10bβ,11β) isomer(11a). Reduction of the methanesulfonate ester of (10a) with lithium aluminium hydride in ether gave 2,8-dimethoxy-4b-methyl-trans-4b,5,6,10b,11,12- hexahydrochrysene (2b), identical with material prepared by another route. Reduction of the methanesulfonate of (4bβ,10bβ,l1β)-2,8-dimethoxy-4b-methyl-4b,5,6,10a,11,12-hexahydrochrysen- 11-ol afforded 2,8-dimethoxy-4b-methyl-cis-4b,5,6,10b,11,12-hexahydrochrysene (12), demethylation of which afforded 4b-methyl-cis-4b,5,6,10b,11,12-hexahydrochrysene-2,8-diol (14b). Dehydration of the mixture of the 11-epimeric alcohols (10a) and (lla) with phosphorus oxytrichloride in pyridine yielded pure 2,8-dimethoxy-4b-methyl-4b,5,6,12-tetrahydrochrysene (6a) which was demethylated with methylmagnesium iodide to give the corresponding dihydroxy compound (9). Other compounds prepared in the course of examining possible routes to (9) and (14b) include 13,13-dichloro-2,8-dimethoxy-4b,5,6,10b,11,12-hexahydro-4b,10b-methanoch rysene (3a), 1-bromo- 2,8-dimethoxy-5,6-dihydrochrysene (5b), and 11-bromo-2,8-dimethoxy-4b-methy1-4b,5,6,12-tetra- hydrochrysene (7). The oestrogenic activities of some of the new angularly methylated hydrochrysenes and of 9α- methyloestradiol (15) are reported.

The structure and function of oestrogens. IV. Synthesis of 17α-ethynyloestradiol specifically polydeuterated in ring C

1983 ◽  
Vol 36 (2) ◽  
pp. 339 ◽  
Author(s):  
DJ Collins ◽  
J Sjovall
Keyword(s):  
Hydrogen Peroxide ◽  
Liquid Ammonia ◽  
Lithium Perchlorate ◽  
Structure And Function ◽  
Prolonged Treatment ◽  
Alkaline Hydrogen Peroxide ◽  
Two Phase ◽  
Lithium Aluminium ◽  
Monosodium Salt ◽  
And Function

Epoxidation of 17,17-ethylenedioxy-3-methoxyoestra-1,3,5(10),9(11)-tetraene( 5) by a two-phase procedure gave the labile 9α,11α-epoxide (11), treatment of which with lithium perchlorate in benzene gave 17,17-ethylenedioxy-3-methoxy-97#946;-oestra-1,3,5(10)-trien-11-one (7). Deuteration of this by prolonged treatment with the monosodium salt of (O,O'-2H2)hydroquinone in dry (O-2H)methanol gave mainly the 98,12,12-trideutero ketone (24) (92% 2H3). Reduction of this with lithium aluminium deuteride to a mixture of the 11-epimeric alcohols (27a) followed by dehydration gave 17,17-ethylenedioxy- 3-methoxy(l1,12,12-2H3)oestra-1,3,5(10),9(11)-tetraene (26) which upon reduction with lithium/ammonia gave 17,17-ethylenedioxy-3-methoxy(11ζ,12,12-2H3)oestra-1,3,5(10)-triene (25). Hydrolysis and demethylation of (25) followed by treatment with potassium acetylide in liquid ammonia yielded 3,17-dihydroxy-19-nor-17a-(11ζ, 12, 12-2H3)pregna-1 ,3,5(10)-trien-20-yne (29) (2H4, 9.2; 2H3, 84.1; 2H3, 3.1; 2H1, 2.2; 2H0, 1.3%). Reduction of the trideutero 9(11)-ene (26) with hexadeuterodiborane followed by treatment with alkaline hydrogen peroxide afforded 17,17-ethylenedioxy-3-methoxy(9α,11β,12,12-2H4)oestra- 1,3,5(10)-trien-11α-ol (30a). Reduction of the corresponding tosylate (30b) with lithium aluminium deuteride, then hydrolysis, demethylation and ethynylation gave 3,17-dihydroxy-19-nor-17α- (9,l 1,11,12,12-2H5)pregna-1,3,5(10)-trien-20-yne (35) (2H5, 84.5; 2H4, 8.5; 2H3, 4.4; 2H2, 0.9; 2H1, 0.8; 2H0, 0.9%).

1-[2-(2-Hydroxymethylphenylthio)benzyl]-4-methylpiperzine and related compounds as potential antidepressants: Synthesis and pharmacological acreening

1984 ◽  
Vol 49 (4) ◽  
pp. 1009-1020 ◽  
Author(s):  
Irena Červená ◽  
Miroslav Protiva
Keyword(s):  
Potassium Carbonate ◽  
Secondary Alcohol ◽  
The Other ◽  
Lithium Aluminium Hydride ◽  
Keto Acid ◽  
Open Model ◽  
Lithium Aluminium ◽  
Neuroleptic Agent ◽  
The One ◽  
Related Compounds

Heating of 1-(2-iodobenzoyl)-4-methylpiperazine (II) with thiophenol and its 2-methyl, 4-methyl, 4-chloro and 2-hydroxymethyl derivatives in dimethylformamide in the presence of potassium carbonate, copper and cuprous iodide gave the piperazides IV-VIII; compound VIII was transformed by reduction with lithium aluminium hydride to the title compound I. The acid IX, obtained by a reaction of 5-chloro-2-iodobenzoic acid with 2-methylthiophenol, was reduced to the alcohol X, which was transformed via the chloride XI to 1-[5-chloro-2-(2-methylphenylthio)-benzyl]-4-methylpiperazine (XII), an open model of the neuroleptic agent clorothepin. Heating of 2,5-dichloroacetophenone with thiosalicylic acid afforded the keto acid XIII whose reaction with 1-methylpiperazine was carried out with the help of N,N"-carbonyldiimidazole. The piperazide XIV obtained was reduced on the one hand with sodium borohydride to the secondary alcohol XV, and with lithium aluminium hydride to 1-(2-[4-chloro-2-(1-hydroxyethyl)phenylthio]benzyl)-4-methylpiperazine (XVI) on the other. None of the dibasic piperazines (I, XII, XVI) did show antireserpine activity. In the general screening, some of the piperazides displayed a mild hypotensive (II, VIII, XIV, XV), adrenolytic (VIII), mild stimulating and antitussic (V), and spasmolytic, antiinflammatory and negatively ino- and chronotropic (XIV) activities.

Ultrastructural effects of exogenous hydrogen peroxide on the myocardium

1989 ◽  
Vol 47 ◽  
pp. 1102-1103
Author(s):  
T. Oguro ◽  
K. Aida ◽  
T. Onodera ◽  
M. Ashraf
Keyword(s):  
Hydrogen Peroxide ◽  
Superoxide Anion ◽  
Osmium Tetroxide ◽  
Structure And Function ◽  
Ultrastructural Changes ◽  
Superoxide Anions ◽  
Isolated Hearts ◽  
Rat Hearts ◽  
And Function ◽  
Isolated Rat

It has been suggested that hydrogen peroxide (H2O2) is indirectly associated with postischemic-reperfusion injury of the heart. Previously, we reported that the heart was not damaged when perfused with exogenously generated superoxide anions. However, H2O2, a dismutation product of superoxide anion severely affected the heart structure and function. In this study, we evaluated the ultrastructural changes of the cel1 membranes in isolated rat hearts and cultured myocytes follow-ing treatment with exogenous H2O2.In the isolated hearts, 300 μM of H2O2, a concentration which was based on our earlier study was perfused for 5 minutes. For the last 2 minutes, 100 mg (2200 U/mg) of horseradish peroxidase was perfused to see the permeability of the cell membranes. In the isolated cultured myocytes, 300 μM of H2O2 was added to the medium for 30 minutes. Both the hearts and the isolated myocytes were fixed with 2.5% buffered glutaraldehyde, postfixed with 1% osmium tetroxide and were processed for electron microscopy.

Tricyclic neuroleptics: Synthesis of metabolites of isofloxythepin and some related compounds

1990 ◽  
Vol 55 (9) ◽  
pp. 2282-2303 ◽  
Author(s):  
Karel Šindelář ◽  
Jiří Jílek ◽  
Josef Pomykáček ◽  
Vladimír Valenta ◽  
Marta Hrubantová ◽  
...  
Keyword(s):  
Formic Acid ◽  
Substitution Reaction ◽  
Lithium Aluminium Hydride ◽  
Enol Ether ◽  
Basic Product ◽  
Lithium Aluminium ◽  
Toluenesulfonic Acid ◽  
Neuroleptic Agent ◽  
Related Compounds ◽  
By Products

The isofloxythepin (I) metabolite IV was synthesized via the acids IX and XI and the esters X and XII. The enamine VIII was prepared from 3-fluoro-8-(2-propyl)dibenzo[b,f]thiepin-10(11H)-one by two methods and was reduced to I. Cloflumide (II) was obtained by reaction of 2,10-dichloro-7-fluoro-10,11-dihydrodibenzo[b,f]thiepin with 3-(1-piperazinyl)propionamide and was oxidized to the sulfoxide XVI. The unsaturated analogue XVII of clopithepin (III) was prepared from 2-chlorodibenzo[b,f]thiepin-10(11H)-one by reaction with 2-bromoethanol in the presence of 4-toluenesulfonic acid in boiling benzene and by the following substitution reaction with 2-(1-piperazinyl)ethanol. An improved synthesis of 6-methyldibenzo[b,f]thiepin-10(11H)-one (XIX) was elaborated. The acid XXVII was synthesized and cyclized with polyphosphate ester. A mixture of compounds was formed from which the ketone XXXVI was isolated and processed by reaction with formamide and formic acid at 200 °C. One of the products was characterized as the formamide XXXIII and was reduced with lithium aluminium hydride to a basic product supposed to be XXXIV. A series of by-products was isolated and characterized. The enamine VIII (V⁄FB-17 156) was found to be a strong neuroleptic agent, similar to isofloxythepin (I). The enol ether XVII (V⁄FB-17 733) was characterized as a mild, practically noncataleptic neuroleptic agent.

Synthesis of N-(1-phenyl-2-propyl)-2,5-diphenylpentylamine and some related compounds as potential neurotropic and cardiovascular drugs

1986 ◽  
Vol 51 (7) ◽  
pp. 1487-1493 ◽  
Author(s):  
Zdeněk Vejdělek ◽  
Jiří Němec ◽  
Miroslav Protiva
Keyword(s):  
Butyric Acid ◽  
Cardiovascular Drugs ◽  
Lithium Aluminium Hydride ◽  
Dibutyl Ether ◽  
Lithium Aluminium ◽  
Related Compounds ◽  
Antiarrhythmic Effects

Heating of 2,5-diphenylvaleric acid with 2-phenylethylamine, 1-phenyl-2-propylamine, 1-phenyl-2-butylamine (IX), 1-(4-methoxyphenyl)-2-propylamine, 1-(4-methoxyphenyl)-2-butylamine (X) and 1-(4-dimethylaminophenyl)-2-propylamine to 200-210 °C resulted in the amides IIb-VIIb which were reduced with lithium aluminium hydride in boiling dibutyl ether to give the amines IIa, IIIa, and Va - VIIa. A similar two-step sequence starting from 4-phenyl-4-(phenylthio)-butyric acid and the amine IX gave compound VIIIa. The salts of the title amines revealed some central stimulating, antireserpine, thiopental potentiating, anticonvulsant, and antiarrhythmic effects. 1-(4-Dimethylaminophenyl)-2-butylamine (XI), prepared in this connection, proved anoretic activity.

Synthesis of racemic and optically active erythro- and threo-9-(2,3,4-trihydroxybutyl)adenines and related compounds

1979 ◽  
Vol 44 (2) ◽  
pp. 593-612 ◽  
Author(s):  
Antonín Holý
Keyword(s):  
Sodium Borohydride ◽  
Sodium Salt ◽  
Sodium Periodate ◽  
Optically Active ◽  
Protecting Groups ◽  
Lithium Aluminium Hydride ◽  
Acidic Hydrolysis ◽  
Lithium Aluminium ◽  
Hydrolysis Of ◽  
Related Compounds

Reduction of diethyl 2,3-O-isopropylidene-DL-tartrate (II) with lithium aluminium hydride afforded 2,2-dimethyl-1,3-dioxolane-threo-4,5-dimethanol (III) which was transformed to the monotosyl derivative VI. Reaction of this compound with sodium salt of adenine, followed by acidic deblocking, gave 9-(DL)-threo-(2,3,4-trihydroxybutyl)adenine (IX). Analogously, 9-(DL)-erythro-(2,3,4-trihydroxybutyl)adenine (XVII) was prepared from diethyl meso-tartrate (XI) via the diol XIII and the tosyl derivative XV. 1,3-O-Benzylidene-D-threitol (D-XVIII) was converted successively into the 4-O-tosyl derivative XIX and the 2-O-benzoyl-4-O-tosyl derivative XX. Reaction of the compound XX with sodium salt of adenine, followed by removal of the protecting groups in the intermediate XXI, afforded 9-(D)-threo-(2,3,4-trihydroxybutyl)adenine (D-XXII); analogously, 1,3-O-benzylidene-L-threitol (L-XVIII) was transformed into the 9-(L)-threo-derivative L-XXII. The D-threo-derivative D-XXII was prepared also from 5-O-tosyl-3-O-benzoyl-1,2-O-isopropylidene-α-D-xylofuranoside (XXIII) or from 3-O-benzyl derivative XXIX by condensation with sodium salt of adenine, followed by acidic hydrolysis, degradation of the 1,2-diol grouping by sodium periodate and sodium borohydride, and methanolysis or hydrogenolysis. An analogous procedure was used for preparation of 1-(D)-threo-(2,3,4-trihydroxybutyl)uracil (D-XXVII). Methyl 2,3-O-isopropylidene-5-benzoyl-6-tosyl-D-mannofuranoside (XXXVI) was transformed to the 5-(adenin-9-yl) derivative XXXVII which after hydrolysis of the dioxolane ring, followed by cleavage of the cis-diol with sodium periodate, reduction with sodium borohydride and methanolysis, afforded 9-(D)-erythro-(2,3,4-trihydroxybutyl)adenine (D-XL). The L-enantiomer (L-XL) was obtained from 5-O-(adenin-9-yl)-3-O-benzoyl-1,2-O-isopropylidene-β-L-arabinofuranoside (XXXIIIb) by acidic cleavage, degradation of the intermediate XXXIV with periodate and methanolysis.

Sign in / Sign up

Export Citation Format

Share Document