Ibrahim F. Zeid

Eudesmane derivatives from Laggera crispata and Pluchea carolonesis

Investigation of the aerial parts of Laggera crispata and Pluchea carolonesis afforded in addition to several known compounds, three new eudesmane derivatives, 3β,4α-dihydroxy-7-epi-eudesm-11(13)-ene, 3α-(2′,3′-dihydroxy-2′-methylbutanoyl)-4,11-dihydroxy-6,7-dehydroeudesman-8-one and 3α-(3′-chloro-2′-hydroxy-2′-methylbutanoyl)cuauhtemone. The structures were elucidated by spectroscopic methods

Synthesis and Anti-HBV Activity of Thiouracils Linked via S and N-1 to the 5-Position of Methyl β-D-Ribofuranoside

Abstract Reverse nucleoside derivatives of 2-(methylsulfanyl)uracils 6a-d were prepared by treating of the sodium salt of 2-(methylsulfanyl)uracils (5a-d) with methyl 2,3-O-isopropylidene-5-O-p-toluenesulfonyl-β-D-ribofuranoside (2). The alkylation of 2-thiouracils 4a-d with methyl 5-deoxy-5-iodo-2,3-O-isopropylidene-D-ribofuranoside (3) afforded the corresponding S-ribofuranoside derivatives 8a-d. Deisopropylidenation of 6a-d and 8a-d afforded the corresponding deprotected derivatives 7a-d and 9a-d, respectively. The Anti-HBV activity of selected compounds was studied.

Synthesis and Antiviral Evaluation of Novel 2,3-Dihydroxypropyl Nucleosides from 2- and 4-Thiouracils

Regioselective alkylation of 2-thiouracils 1a–c and 4-thiouracils 7a,b with 2,3-O-isopropylidene-2,3-dihydroxypropyl chloride (2) afforded 2-{[(2,2-Dimethyl-1,3-dioxolan-4-yl) methyl]thio}pyrimidin-4(1H)-ones 3a–c and 4-{[(2,2-Dimethyl-1,3-dioxolan-4-yl)methyl]thio} pyrimidin-2(1H)-ones 8a,b, respectively. Further alkylation with 2 and/or 2,3-O-isopropylidine-1-O-(4-toluenesulfonyl)-glycerol (4) gave the acyclo N-nucleosides 5a–c and 9a,b whose deprotection afforded 6a–c and 10a,b. 2-(Methylthio)pyrimidin-4(1H)-ones 11a–c and 4-(methylthio)pyrimidin-2(1H)-ones 14a,b were treated with 2 and/or 4 to give 12a–c and 15a,b which were deprotected to give 13a–c and 16a,b. Pyrimidine-2,4(1H,3H)-dithiones 17a–c were treated with two equivalents of 2 to give 2,4-bis{[(2,2-dimethyl-1,3-dioxolan-4-yl)methyl]thio}pyrimidines 18a–c. Deprotection of compounds 18a–c gave 2,4-bis[(2,3-dihydroxypropyl)thio]pyrimidines 19a-c. The activity of the deprotected nucleosides against Hepatitis B virus was evaluated and showed moderate inhibition activity against HBV with mild cytotoxicity.

New acylated flavone and cyanogenic glycosides from Linum grandiflorum

The first investigation of Linum grandiflorum resulted in the isolation of one new acylated flavone O-diglycoside known as luteolin 7-O-α-D-(6′″-E-feruloyl)glucopyranosyl (1 → 2)-β-D-glucopyranoside, and one new cyanogenic glycoside known as 2-[(3′-isopropoxy-O-β-D-glucopyranosyl)oxy]-2-methylbutanenitrile, together with four known flavonoid glycosides, three known cyanogenic glycosides and one alkyl glycoside. The new compounds were structurally elucidated via the extensive 1D, 2D NMR and DIFNOE together with ESI-TOF-CID-MS/MS and HR-MALDI/MS.

Synthesis of New Thiolated Acyclonucleosides with Potential Anti-HBV Activity

Treatment of the sodium salt of compounds 1, 7 or 12 with chloroethyl methyl ether, 2-chloroethyl toluoylate or 2-(2-chloro ethoxy)ethyl acetate afforded the corresponding derivatives 2, 3, 4, 8, 9, 13 and 14. Ammonolysis of 3, 4, 9 and 14 at room temperature gave the corresponding hydroxyalkyl derivatives 5, 6, 10, 11, and 15, respectively. Alkylation of 2,4-dithiouracil gave 2,4-dialkylthio pyrimidine.

The ritter reaction of α-chlorocarbenium ions; a synthesis of chloro substituted 2-azoniaallene salts

Abstract α-Chlorocarbenium ions, 9 , stabilized by allylic resonance, react with nitriles, 10 , to give chloro substituted 2-azoniaallene salts, 12 . The cation 12k abstracts chloride from the counterion SbCl 6 − to furnish the chloroimine 13k together with SbCl 5 . The hexachloroantimonates 12 can be transformed into unpolar chlorides, 13b,1 , and 17 , with ammonium chlorides. Compounds 13 and 17 are hydrolyzed to give N-acyl imidoyl chlorides, 14a,b , respectively the allophanate 18 . Electron-rich nitriles insert into the CCl bond of the 2-azoniaallene salts 12 to afford imidoyl chlorides, 151-p,16 .

Chemistry of phosphorus ylides. Part 38: Synthesis and anticancer activity of cyclobutane, oxaphosphetane, oxaphosphinine, azaphosphetidene, and pyridazine derivatives

The reactions of nucleophilic active phosphacumulene, phosphallene, and stable phosphonium ylides with quinones, cyclobutenone, α,β-unsaturated compounds, quinone monoanil, and monohydrazone were investigated. Carbocyclic and heterocyclic patterns such as phosphanylidene cyclobutanones, oxaphosphetane, oxaphosphinines, azaphosphetidenes, and pyridazines were obtained. The cytotoxic activity of some new products was evaluated against human cervical and breast carcinoma cell lines. Certain tested compounds showed promising results.Graphical abstract

Anti-Hepatitis B Virus Activity of New Substituted Pyrimidine Acyclic Nucleoside Analogues

A number of N-substituted pyrimidine acyclic nucleosides were synthesized by coupling reaction of 2-(2-chloroethoxy)ethyl acetate or (2,2-dimethyl-1,3-dioxolan-4-yl)methyl 4-methylbenzenesulfonate with the corresponding base followed by deprotection. The synthesized compounds were tested for their antiviral activity against hepatitis B virus (HBV). The plaque reduction infectivity assay was used to determine virus count reduction as a result of treatment with the synthesized compounds which showed moderate to high antiviral activities

On the Reaction of α,α-Dichlorocarbenium Ions with Isocyanates

Trichlormethanes 4 react with two equivalents of n-alkyl isocyanates R2-NCO in the presence of SbCl5 to furnish the 2,2-dichloro-5,6-dihydro-6-oxo2H-1,3,5-oxadiazinium salts (9). The structure of these heterocycles is confirmed by an X-ray analysis of 9d (R1 = ClC = CCl2, R2 = Et). p-Tolyl isocyanate is Friedel-Crafts alkylated by 4b in the presence of SbCl5. Subsequent ring closure affords the quinolinium salt 13, which is hydrolyzed to give inter alia the quinolone 16.

Facile Synthesis of Non-nucleoside Compounds Starting from α-Chlorocarbenium Ions and Isocyanates as Potential HIV-1 Reverse Transcriptase Inhibitors

Chloro(phenyl)carbenium hexachloroantimonate salts react with isocyanates to afford either isoindolium (1) or benzoxazinium salts (2). Addition of one equivalent of alcohol to 2 led, after hydrolysis with aq. NaOH, to the formation of benzoxazin-2-ones 3. Treatment with a large excess of alcohol transformed the salts 1 and 2 to the corresponding isoindol-1-ones 11 and the isocyanates 5, respectively. Reaction of 5 with primary amines furnished the urea derivatives 6 in good yield. The biological activity of 6a - o against HIV-1 was determined. Graphical Abstract Facile Synthesis of Non-nucleoside Compounds Starting from α-Chlorocarbenium Ions and Isocyanates as Potential HIV-1 Reverse Transcriptase Inhibitors