Angel Guzman

Cross-Coupling Reactions of Monosubstituted Acetylenes and Aryl Halides Catalyzed by Palladium on Charcoal

Abstract A convenient procedure for the Pd(O) catalyzed cross-coupling of monosubstituted acetylenes with aryl halides, in which palladium on charcoal serves as the source of the noble metal is described.

Synthesis and cytotoxic activity of 2-methylimidazo[1,2-a]pyridine- and quinoline-substituted 2-aminopyrimidine derivatives

A series of 2-methylimidazo[1,2-a]pyridine- and quinoline-substituted 2-aminopyrimidines derivatives were synthesized using a convenient synthetic route. We evaluate the isosteric replacement of methyl groups in 4-(2-methylimidazo[1,2-a]pyridin-3-yl)-N-p-tolylpyrimidin-2-amine (compound 1) by trifluoromethyl groups and the isosteric substitution of the 2-methylimidazo[1,2-a]pyridin-3-yl scaffold by quinolin-4-yl or quinolin-3-yl moieties. The replacement of hydrogen by fluorine does not affect notably the cytotoxic activity and CDK inhibitor activity in this series. Quinolin-4-yl-substituted compound, 8, presents cytotoxic activity and is most effective and selective against CDK1/CycA than against CDK2/CycB. Compound 11, which has a quinolin-3-yl moiety is CDK inhibitor but presents null cytotoxic activity. Quinolin-4-yl-substituted compounds constitute a new lead of cytotoxic and CDK inhibitor compounds from which more compelling and selective inhibitors can be designed.

6-Substituted 2-(N-trifluoroacetylamino)imidazopyridines induce cell cycle arrest and apoptosis in SK-LU-1 human cancer cell line

A series of 6-substituted 2-(N-trifluoroacetylamino)imidazopyridines have been synthesized and their bioactivities were evaluated. Compounds 6a, 6c, and 11a were the most active compounds with modest cytotoxic activity against six human cancer cell lines U251 (glioma), PC-3 (prostate), K-562 (leukemia), HCT-15 (colon), MCF7 (breast) and SK-LU-1 (lung). The cell cycle analysis showed that compounds 6a, 6c, and 11a induce a G2/M phase cell cycle arrest on SK-LU-1 cell line where inhibition of CDK-1 and CDK-2 may be implicated.

Synthesis of pyrimidines from 2-trichloromethyl-4-dimethylamino-1,3-diaza-1,3-butadienes and electron deficient acetylenes☆

Abstract 2-Trichloromethyl-4-dimethylamino-1,3-diaza-1,3-butadienes(3), prepared from trichloroacetamidine(1) and amide acetals 2, readily react with electron deficient acetylenes 4 to give 2-trichloromethylpyrimidines 5. 1,3-Diaza-1,3-dienes 3 undergo [4π+2π] cycloaddition with activated acetylenes 4 providing pyrimidines 5.

Synthesis and gastric antisecretory properties of allenic 16-phenoxy-omega-tetranor prostaglandin E analogs

In order to improve the modest oral activity of PGE2 as an inhibitor of gastric acid secretion, analogs were prepared and tested orally in histamine-challenged rats. Insertion of a double bond at C-4, resulting in the 4,5-allene analog of PGE1, gave a small increase in activity. Introduction of the omega-tetranor-16-phenoxy lower sidechain, a modification known to enhance activity in the PGF series, gave an eight-fold increase in activity. The analog having both modifications (enprostil, 2) showed a six hundred-fold increase in oral antisecretory activity over PGE2, which may reflect a potentiation effect. Modification of enprostil at C-1 (various esters) and at C-11 (11-methyl, 11-deoxy) generally resulted in compounds of high activity while modifications at other sites generally resulted in significant reductions in activity.

Synthesis of Aryl Phosphonates by Reaction of Grignard Reagents with Diethyl Cyanophosphonate

Abstract Reaction of Grignard reagents with diethyl cyanophosponate gave aryl phosphonates under mild conditions and in good yield

A Convenient Method for the Phosphorylation of Phenols with Diethyl Cyanophosphonate

Abstract Phosphorylation of phenols with diethyl cyanophosphonate in methylene chloride solution at 0°C is an easy, rapid and good yielding reaction.

Absolute structures of zaluzanines A and B

Abstract2D NMR,1H and13C as well as single crystal X-ray studies were performed in order to establish the correct configuration of all assymetrical centers in the zaluzanines A and B. This work enabled us to correct the previously proposed absolute configuration at the C-5 and C-6 centers, obtained by chemical correlations. Crystals of zaluzanin B (1c) are orthorhombic witha=6.8176(6),b=12.870(2), andc=18.507(5) Å, space groupP212121 and the crystals of the carbodibromo derivative of zaluzanin A diacetate (4) are also orthorhombic witha=14.6123(5),b=15.1218(4), andc=19.9384(4) Å, space groupP21212.

2D 1H and 13C NMR evidences of the [2+2] autodimerization of 2-benzyl-5-benzylidene cyclopentanone yielding two different diphenyl, dispiro cyclobutane derivatives

The ene-ene [2 + 2] cycloaddition of 2-benzyl-5-benzylidenecyclopentanone proceeds smoothly and spontaneously in benzene-d6 or deuteriochloroform solution to give two different diphenyl dispiro [4.1.4.1] dodecan-4,11-diones. Detailed 1H and 13C 2DNMR spectroscopy (COSY, HMQC, HMBC) were performed in order to prove the existence in solution of two cyclobutane derivatives, one a previously described photodimer obtained by the UV irradiation of crystals of 2-benzyl-5-benzylidenecyclopentanone.

A congener study of zileuton reveals interesting effects on glucuronidation rates

Abstract Heteroatom substitution within the zileuton nucleus led to a congener series which was evaluated for potency and rate of glucuronidation, a major route for elimination of zileuton. Subtle changes in structure were found to significantly effect glucuronidation rate.