Synthesis and Absolute Configuration of Pyriculol

A total synthesis of optically active pyriculol is described. The Wittig reaction between an aldehyde 19 and a triphenylphosphonium ylide 12 gave an intermediate 20. Successive treatment of 20 with p-toluenesulfonic acid, active manganese dioxide, and potassium carbonate gave (3′R,4′S)-pyriculol (23), which was identical with natural pyriculol (1) in all respects. From this synthesis, the absolute stereochemistry of pyriculol (1) was determined to be 2-[(3′R,4′S)-3′,4′-dihydroxy- (1′E,5′E)-1′,5′-heptadienyl]-6-hydroxybenzaldehyde     

Synthesis and Analysis of Nucleosides Bearing Pyrrolepolyamide Binding to DNA

Abstract

An efficient synthesis of adenosine bearing pyrrolepolyamide 1 was achieved by coupling of 3 with 2. The CD spectra obtained at several [ligand ]/[duplex] ratios allowed verification of the formation complex of the DNA duplex [d(CGCAAATTGGC)/d(GCCAATTTGCG)] with 1.     

Synthesis of 1, 7-Dideazapurine Ribonucleosides and Deoxyribonucleosides

Abstract

The synthesis of hydroxylamino derivatives of 1,7-dideazaadenosine and of 1,7-dideaza-2′-deoxyadenosine, starting from 4-nitro-1H-pyrrolo[2,3-b]pyridine (1), is described. None of the synthesized compounds are substrates of adenosine deaminase and two of them (3 and 18) are weak inhibitors.     

Improved Synthesis of 2′-Amino-LNA

Abstract

2′-Amino-LNA phosphoramidite (10) was synthesised by means of a new strategy, which is convergent with the synthesis of 2′-oxy-LNA up until a late stage intermediate (1).     

Synthesis of orthogonally protected l-threo-β-ethoxyasparagine

Orthogonally protected l-threo-β-ethoxyasparagine (Fmoc-EtOAsn(Trt)-OH, 1) was synthesized from diethyl (2S,3S)-2-azido-3-hydroxysuccinate 2 in eight steps as a building block for solid-phase peptide synthesis. The starting material is easily available in multi-gram scale from d-diethyltartrate. The transformation steps reported here are robust and scalable. Thus, a significant amount of 1 (1.8 g) was obtained in 21% overall yield. The synthesis reported is also expected to be useful for the preparation of other O-substituted l-threo-β-hydroxyasparagine derivatives.     

Synthesis and Testing of New Modified Nucleosides

Abstract

New efficient routes for the high-yielding synthesis of several classes of modified nucleosides have been developed. We have prepared both the D- and L-enantiomers of the methylene-expanded oxetanocin isonucleosides 1a-c and the L-2′,3′-dideoxy isonucleosides 2abc (both the oxa and thia analgoues) as well as new routes for the preparation of L-ribose and 2-deoxy L-ribose 3ab and their modified nucleosides 4.     

Asymmetric Synthesis and Sensory Evaluation of Sedanenolide

The synthesis and sensory evaluation of enantiomeric sets of sedanenolide (1) and 3-butylphthalide (3) are described. The asymmetric synthesis was achieved via the intramolecular Diels-Alder reaction of chiral propargylester (5) which was prepared from optically active propargyl alcohol (4) and 2,4-pentadienoic acid. The sensory evaluation of these enantiomers revealed that there were distinct differences between their aroma character and odor threshold.     

Synthesis of Novel Olefinic Carbocyclic Purine Nucleoside Analogues

Abstract

The synthesis of optically pure unsaturated carbocyclic nucleoside analogues is described. (3,4S)-Bis(t-butyldiphenyl silyloxymethyl)-1R and 1S cyclopent-2-en-1-ol were coupled with 6-chloropurine and 2-amino-6-chloropurine respectively, using a modified Mitsunobu reaction. The products were reacted further using standard procedures to give compounds 12, 14, 16 and 18.     

Synthesis and anti-cancer activity evaluation of new aurone derivatives

Abstract

In this study, we have synthesized 2-[3- or 4-(2-aryl-2-oxoethoxy)arylidene]benzofuran-3-one derivatives (D1–D38) and evaluated their anti-cancer activities. The final compounds were obtained in multistep synthesis reactions using benzofuranon-3-one derivatives (A1–A4, B) as starting materials which were gained in various synthetic ways. Aurone derivatives (C1–C10) were acquired with the condensation reaction of these starting materials and 3-/4-hydroxybenzaldehyde which were then reacted with α-bromoacetophenones to get final compounds. The anti-cancer activity of the selected compounds was performed by National Cancer Institute (NCI), USA against 60 human tumor cell lines derived from nine neoplastic diseases. Compounds exhibited anti-cancer activity in varying ratios.     

Synthesis and Biological Activity of ( + )-Pyrenolide B

The synthesis and biological activity of ( + )-pyrenolide B (1) and related compounds are described. The known (Z)-2-decen-9-olide (7) prepared via decan-9-olide (6) from 2-ethoxycarbon- ylcyclononanone (4) was converted to 9 by the deconjugative process, which, upon oxidation with m-chloroperbenzoic acid, led to the epoxy lactone 10. Base-promoted epoxide ring opening of 10 and subsequent oxidation furnished keto lactone 8, which, on treatment with phenylselenenyl chloride and subsequent oxidative elimination, provided ( + )-pyrenolide B (1). The antimicrobial activity of (±)-1, 6, 7, 8, 9, 10a, 10b and 11a was examined against fungi and yeast.     

Synthesis and anticancer activity of some 1,2,3-trisubstituted pyrazinobenzimidazole derivatives

Abstract

The synthesis of some new pyrazino[1,2-a]benzimidazole derivatives and investigation of their anticancer activities were aimed in this work. Thus, 2-acetylbenzimidazole was reacted with appropriate α-bromoacetophenones and potassium carbonate in acetone to give 2-(2-acetyl-1H-benzimidazol-1-yl)-1-phenylethanone derivatives (3a–d). These diketone compounds were reacted with varied benzylamines in acetic acid to obtain 2-benzyl-1-methylidene-3-aryl-1,2-dihydropyrazino[1,2-a]benzimidazole derivatives (4a–t). The structures of the obtained compounds were elucidated by using IR, ¹H-NMR, ¹³C-NMR, MS spectral data and elemental analyses results. Anticancer activities of the selected compounds were investigated in National Cancer Institute, Bethesda, MD. 3c and 4n showed remarkable anticancer activity comparing with standard drugs, melphalan and cisplatin.     

Synthesis and Antiviral Activity of Some N-Pentopyranosyl-2-Pyridinethiones

Abstract

A novel synthesis of 1-(β-D-pentopyranosyl)pyridinethione nucleosides utilizing pyridine-2(1H)-thiones and α-bromoxylose or β-bromoarabinose triacetate as starting components is described. The free nucleosides were tested for their potential activity against HIV and different types of tumor virus.     

Synthesis of 3′,5′-Dithymidylyl-α-hydroxyphosphonate Dimer Building Blocks for Oligonucleotide Synthesis—A New Pro-oliguncleotide

Abstract

The synthesis of the dimer building blocks 1 and 2 and their introduction into (T)₁₅-oligonucleotides is described. The stability against 3′-exonuclease digestion (SVP) as well as the hybridization properties (T_m values) were examined.     

Nucleosides,IV1 Synthesis and Properties of 2-Metylthio-Naphthimidazole-Ribonucleoside

Abstract

The synthesis of 2-Methylthio-1-(β-D-ribofuranosyl) naphthimidazole has been accomplished by condensation of 2-methylthio-1-trimethylsilylnaphthimidazole(3) with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose(4) in the presence of trimethylsilyl triflate in 1,2-dichloroethane, followed by subsequent debenzoylation. Structural proofs are based on elementary analysis, UV- and ¹H-NMR-spectra.     

Chemical and Enzymatic Synthesis and Antiviral Properties of 2′-Deoxy-2′-fluoroguanosine

Abstract

Chemical and enzymatic methods were employed for the synthesis of the title compound, 2′F-Guo 7. High antiviral activity of 2′F-Guo was established in chick embryo cells infected with influenza virus FPV/Rostock/34 (H7N1) and herpes simplex virus (HSV) type I (1C strain).     

Synthesis of Some Pyridine Ribosides and Their Biological Activity

Abstract

A synthesis of 1-(β-D-ribofuranosyl)-pyridin-2-thiones via reaction of 3-cyanopyridin-2(H)-thiones with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide under basic conditions, followed by hydrolysis with methanolic ammonia is reported.     

Synthesis of Protected 3′,5′-Di-2′-Deoxythymidine-(α-hydroxy-2-nitrobenzyl)-phosphonate Diesters as Dimer Building Blocks for Oligonucleotides

Abstract

The synthesis of 3′-succinyl-CPG bound 3′,5′-di-2′-deoxythymidyl-(α-hydroxy-2-nitrobenzyl)-phosphonate diester 1 and the 3′-phosphoamidite derivative 2 is descibed. The hydroxyl-groups of the backbone modification were protected with trialkylsilyl groups: TES and TBS. Compounds 1, 2 are suitable blocks for oligonucleotide synthesis.     

Synthesis of Thymine Nucleosides Derived from 1-Deoxy-D-psicofuranose

Abstract

The use of D-(+)-ribonic γ-lactone 1a,b as a chiral synthon leads to an efficient synthesis of the ketose 1-deoxy-D-psicofuranose 2a,b. Condensation of the corresponding acetyl derivative 3a,b with silylated thymine, followed by deprotection of 4a,b affords an anomeric mixture of ketosyl nucleoside 6 (predominately the β-anomer) in an improved overall yield of 49%.     

A Versatile Synthesis of Enantiomerically Pure D- and L-Pyranosyl Nucleoside Analogues

Abstract

2-[[O-(p-Methoxybenzyl)-oxy]methyl]-5,6-dihydro-1,4-dithiin 1 is a versatile three carbon homologation reagent which has been conveniently used in the synthesis of enantiomerically pure modified nucleosides.     

Design,Synthesis, and Antiviral Evaluation of Some Polyhalogenated Indole C-nucleosides

2,5,6-Trichloro-1-(β-D-ribofuranosyl)benzimidazole (TCRB), 2-bromo-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole (BDCRB) and 2-benzylthio-5,6-dichloro-1-(β-D-ribofuranosyl)benzimidazole (BTDCRB) are benzimidazole nucleosides that exhibit strong and selective anti-HCMV activity. Polyhalogenated indole C-nucleosides were prepared as 1-deaza analogs of the benzimidazole nucleosides TCRB and BDCRB. A mild Knoevenagel coupling reaction between an indol-2-thione and a ribofuranose derivative was developed for the synthesis of 2-benzylthio-5,6-dichloro-3-(β-D-ribofuranosyl)indole (12). 3-(β-D-ribofuranosyl)-2,5,6-trichloroindole (16) was prepared from 12 in 4 steps. A Lewis acid-mediated glycosylation method was then developed to prepare the targeted 2-haloindole C-nucleoside 16 stereoselectively in four steps from the corresponding 2-haloindole aglycons. Only 12 was active against HCMV but it also was somewhat cytotoxic.