Vasilios H. Pavlidis

Synthesis and anticancer activities of 4-oxobenzopyrano[2,3-d]pyrimidines.

Several 2-aryl-4-oxoxbenzopyrano[2,3-d]pyrimidines have previously been shown to exhibit in vivo antitumor activity in mice with P388 lymphocytic leukemia. In the present study, a series of novel substituted benzopyrano[2,3-d]pyrimidines have been prepared and tested for cytotoxic activity against a panel of cancer cell lines including the P388 lymphocytic leukemia cell line. The unsubstituted parent compound, some methoxylated derivatives and a cyclohexyl derivative all exhibited potent cytotoxic activity (IC50 values 0.3-0.64 microM). A number of derivatives, including the unsubstituted parent pyrimidine, were shown to cause a significant perturbation in cell cycle kinetics with an observed 2- to 3-fold increase in cells in the G2/M phase of the cell cycle. Furthermore, a polymethoxylated derivative, 2-(3,4,5-trimethoxyphenyl)-9-methoxy-4-oxo-2,3-dihydrobenzopyrano[ 2,3-d]pyrimidine 13, was shown to be selectively active against a number of human ovarian cell lines.

Synthesis of cytotoxic furonaphthoquinones: Regiospecific synthesis of diodantunezone and 2-ethylfuronaphthoquinones

Abstract Diodantunezone was first isolated from Lantana achyrantifolia (Verbenaceae) and originally assigned as 8-hydroxy-4,9-dihydronaphtho[2,3-b]furan-4,9-dione 1a but its structure was later revised to 5-hydroxy-4,9-dihydronaphtho[2,3-b]furan-4,9-dione 2a. The regiospecific synthesis of diodantunezone 2a and its methyl ether, 5-methoxy-4,9-dihydronaphtho[2,3-b]furan-4,9-dione 2b, is described. The preparation of two 2-ethylfuronaphthoquinones 14a and 14b is also described. All four quinones were shown to posses cytotoxic activity against three cell lines (1.3–17.4 μmol dm−3).

The Rapid Reduction of α,α-Diaryl Alcohols To The Corresponding Alkanes Using lodotrimethylsilane

Abstract The utility of iodotrimethylsilane has been extended to include the rapid and highly selective reduction of α,α-diaryl alcohols. The reduction of a series of α-hydroxyfuroic acids in near quantitative yield has been demonstrated and the mechanism discussed.

The Synthesis of a Novel Series of Substituted 2-Phenyl-4H-3,1-benzoxazin-4-ones

Abstract Following initial studies1 on a substituted 2-[3-methylphenyl]-4H-3,1-benzoxazin-4-one showing some cytotoxic activity, the synthesis of a novel series of 2-phenyl substituted 4H-3,1-benzoxazin-4-ones is reported herein.

Spirodienones. Part 5. The synthesis and reactions of N-sulphonylcyclohexadienimines

The anodic or chemical oxidation of para-substituted sulphonanilides gives 4,4-disubstituted N-sulphonylcyclohexadienimines, which, from appropriately substituted anilines, may be spirocyclic. The scope and limitations of the synthesis are described, and a mechanism proposed. The selective hydrolysis of the dienimines to the corresponding dienones provides a convenient route to the latter compounds. The reaction of some of the dienimines with dienes is discussed.

Synthesis of Cytotoxic Pyrrolo[1,2-a]-benzimidazol-1-ones

Abstract Several pyrrolo[1,2-a]benzimidazol-1-ones have been synthesised and shown to be cytotoxic to two mammalian cell lines. A synthesis of the novel ring system isoindolo[1,2-a]benzimidazol-1-one is described.

Structure-activity studies on 2-aryl-4H-3,1-benzoxazin-4-ones.

Eight benzoxazin-4-ones related In structure to NSC 341964 (1) have been tested for cytotoxlclty In two different cell systems. Two of the benzoxazln-4-ones (3 and 10) showed good cytotoxlclty (ID50 =9.9 and 8.9 µM) In P388 cells. The nltrobenzoxazln-4-one (10) caused a significant alteration in cell cycle distribution when administered to P388 cells and was an inhibitor of porcine pancreatic elastase. Structure-activity relationships are discussed.

The Regiospecific C‐3 Lithiation of 5‐Ethyl‐2‐furoic acid: An Approach to Key Natural Product Intermediates

Treatment of 5-ethyl-2-furoic acid with n-butyl-lithium in tetrahydrofuran gave regiospecific C-3 lithiation, whereas treatment of the same acid with lithium di-isopropylamide (LDA) afforded only starting material. The synthetic utility of dilithiated 5-ethyl-2-furoic acid has been demonstrated with the synthesis of two substituted 3-benzyl-5-ethyl-2-furoic acid derivatives which are key intermediates for the preparation of naturally occurring cytotoxic 2-ethylfuronaphthoquinones. Reaction of the C-3 lithiated species with two equivalents of benzaldehyde and subsequent reduction affored the corresponding 3-benzyl-5-ethyl-2-furoic acids. An alternative route to 5-ethyl-2-furoic acid has been described allowing for a more convenient preparation of longer-chain 5-alkyl-2-furoic acids.

Efficient regiospecific synthesis of two cytotoxic furonaphthoquinones, 5,7-dimethoxy-4,9-dihydronaphtho[2,3-b]furan-4,9-dione and 5,6,7-trimethoxy-4,9-dihydronaphtho[2,3-b]furan-4,9-dione

Following the recent isolation of several furonaphthoquinones from two Latana species (Verbenaceae), a novel synthetic method for the preparation of two cytotoxic furonaphthoquinones, 5,7-dimethoxy-4,9-dihydronaphtho[2,3-b]furan-4,9-dione 8a and 5,6,7-trimethoxy-4,9-dihydronaphtho[2,3-b]furan-4,9-dione 8b is described. The title compounds were obtained in high overall yield via hydrogen peroxide oxidation of intermediate 4-hydroxy-9-trifluoroacetylnaphthofurans. Both the title compounds exhibit cytotoxic activity towards three mammalian cell lines (2.99–6.6 µmol dm–3).