Synthesis and structural characterization of the 5-(2-haloethyl)pyrimidines--hydrogen-bonded chains in alpha-(1-carbamyliminomethylene)-gamma-butyrolactone.

Three novel 5-(2-haloethyl)pyrimidine derivatives were synthesized and characterized by 1H-NMR, 13C-NMR, MS, IR spectra and elemental analysis. Iodine and chlorine atoms in the C-5 side chain were introduced by reaction of 5-(2-hydroxyethyl)pyrimidine with hydroiodic acid and phosphoryl chloride, respectively. The structure of the intermediate alpha-(1-carbamyliminomethylene)-gamma-butyrolactone was determined by X-ray crystal structure analysis.

Synthesis, cytostatic and anti-HIV evaluations of the new unsaturated acyclic C-5 pyrimidine nucleoside analogues.

A series of the novel C-5 alkynyl pyrimidine nucleoside analogues (1-14) in which the sugar moiety was replaced by the conformationally restricted Z- and E-2-butenyl spacer between the phthalimido and pyrimidine ring were synthesized by using Sonogashira cross-coupling reaction. Cytostatic activity evaluation of the novel compounds showed that E-isomers exhibited, in general, better cytostatic activities than the corresponding Z-isomers. E-isomer 14 exhibited the best cytostatic effect against all evaluated malignant cell lines, particularly against hepatocellular carcinoma (Hep G2, IC(50)=4.

Synthesis and antiviral and cytostatic evaluations of the new C-5 substituted pyrimidine and furo[2,3-d]pyrimidine 4',5'-didehydro-L-ascorbic acid derivatives.

The novel C-5 alkynyl substituted pyrimidine (1-11) and furo[2,3-d]pyrimidine derivatives (12-22) of l-ascorbic acid were synthesized by coupling of 5-iodouracil-4',5'-didehydro-5',6'-dideoxy-l-ascorbic acid with terminal alkynes by using Sonogashira cross-coupling reaction conditions. The new compounds were evaluated for their cytostatic and antiviral activities. Among all evaluated compounds, the octynyl-substituted uracil derivative of l-ascorbic acid (3) exhibited the most pronounced cytostatic activities against all examined tumor cell lines (IC50 = 2-12 microM).

The novel C-5 aryl, alkenyl, and alkynyl substituted uracil derivatives of L-ascorbic acid: synthesis, cytostatic, and antiviral activity evaluations.

The novel C-5 substituted uracil derivatives of l-ascorbic acid were synthesized by coupling of 5-iodouracil-4,5-didehydro-5,6-dideoxy-l-ascorbic acid with unsaturated stannanes under Stille reaction conditions. The new compounds were evaluated for their antitumoral and antiviral activities. Among all compounds evaluated the 5-propynyl substituted uracil derivative of l-ascorbic acid (7) exhibited the most pronounced cytostatic activities against all examined tumor cell lines (IC(50): 0.

Synthesis, structural studies, and cytostatic evaluation of 5,6-di-O-modified L-ascorbic acid derivatives.

The 5,6-di-O-tosylated derivative of l-ascorbic acid was synthesized by selective protection and deprotection of 2,3- and 5,6-dihydroxy functional groups involving 5,6-ditosylation in the final step, while the novel 6-acetoxy, 6-hydroxy, and 6-chloro derivatives of 4,5-didehydro-l-ascorbic acid were obtained by reaction of ditosylated compound with nucleophilic reagents. The analysis of 3JH-4-H-5 homonuclear coupling constants shows that all l-ascorbic acid derivatives except for epoxy and 4,5-didehydro compounds exist in high population as gauche conformers across C-4-C-5 bonds, while 3JC-3-H-5 heteronuclear coupling constants in 4,5-didehydro derivatives indicate cis geometry along C-4-C-5 double bond. The X-ray crystal structure analysis of 2,3-di-O-benzyl-5,6-epoxy- and 5,6-isopropylidene-l-ascorbic acid shows that the oxygen atoms attached at positions 2 and 3 of the lactone ring are disposed in a synperiplanar fashion.

The novel pyrimidine and purine derivatives of l-ascorbic acid: synthesis, one- and two-dimensional 1H and 13C NMR study, cytostatic and antiviral evaluation.

The syntheses of the novel C-5 substituted pyrimidine derivatives of l-ascorbic acid containing free hydroxy groups at C-2' (6-10) or C-2' and C-3' (11-15) positions of the lactone ring are described. Debenzylation of the 6-chloro- and 6-(N-pyrrolyl)purine derivatives of 2,3-O,O-dibenzyl-l-ascorbic acid (16 and 17) gave the new compounds containing hydroxy groups at C-2' (18) and C-2' and C-3' (19 and 20). Z- and E-configuration of the C4'C5' double bond and position of the lactone ring of the compounds 6-9 were deduced from their one- and two-dimensional (1)H and (13)C NMR spectra and connectivities in NOESY and HMBC spectra.

Synthesis and biological evaluation of iodinated and fluorinated 9-(2-hydroxypropyl) and 9-(2-hydroxyethoxy)methyl purine nucleoside analogues.

The novel fluorinated and iodinated purine derivatives containing 9-(2-hydroxypropyl) (1a-7a and 9a-13a) and 9-(2-hydroxyethoxymethyl) (1b-3b, 5b, and 7b-12c) side chains were synthesized by a multistep synthetic route involving Baltz-Schiemann's fluorination and diazotation/iodination as key reactions. An unequivocal proof for the stereostructure of 5b was obtained by X-ray structure analysis. New compounds were evaluated for their cytostatic activity against murine leukemia (L1210); mammary carcinoma (FM3A); and human T-lymphocytes (Molt4/C8 and CEM), melanoma (HBL), cervical carcinoma (HeLa), colon carcinoma (HT29 and SW620), laryngeal carcinoma (Hep2), and pancreatic carcinoma (MiaPaCa2) as well as diploid fibroblasts (WI38).