Di-ddU-α-Hydroxyphosphonate and α-Hydroxy- α- METHYLPHOSPHONATES as Potential Prodrugs of Antiviral Nucleoside Analogues

Abstract

The synthesis of a potential new prodrug system for the antiviral nucleoside ddU 1 based on α-hydroxybenzylphosphonates 2 and 3 is described. In principle, 2, 3 are able to hydrolyze via different mechanisms yielding ddU H-phosphonate 4 or ddU monophosphate 5, respectively.     

An Efficient Synthesis of Methyl Jasmonate and Methyl Dihydrojasmonate

A simple and an efficient synthesis of methyl jasmonate (1) and methyl dihydrojasmonate (5) is described. Starting from alkyl acetoacetate or acetonedicarboxylate, 1 and 5 were obtained in only a few steps via intramolecular Michael addition.     

Alternate Approaches to the Synthesis of 2′-O-Me Nucleosides

Abstract

Three different approaches to the synthesis of 2′-O-methyl nucleosides starting from the corresponding nucleoside or commercially available 1,2:5,6-di-O-isopropylidene-α-D-allofuranose 1 are described.     

Homo Dinucleoside-α-hydroxyphosphonate Diesters as Prodrugs of the Antiviral Nucleoside Analogues 2′,3′-Dideoxythymidine and 3′-Azido-2′,3′-dideoxythymidine

Abstract

The synthesis of a new prodrug system for antiviral nucleosides AZT (1) and ddT (2) based on α-hydroxybenzylphosphonates 3 is described. 3 hydrolyze via different mechanisms yielding the H-phosphonate monoesters 4 or nucleoside monophosphates 5, respectively. 3 were more lipophilic than 1, 2 and showed marked activity against HIV-1/2.     

SYNTHESES OF NOVEL SUBSTITUTED-BORANOPHOSPHATE NUCLEOSIDES

ABSTRACT

A number of substituted (borano) nucleic acids, 3′-[diethylphosphite-(cyano, carboxy, or carbamoyl) borano] deoxynucleosides (3a–4c) and 5′-[diethylphosphite(cyano or carboxy) borano] deoxynucleosides (6a–7d) were prepared by a variety of synthetic procedures. The syntheses of the pyrophosphates (2a–2c), as precursors for 3a–4c, are also described.     

Six new species of <Emphasis Type="Italic">Timonius</Emphasis> (Rubiaceae: Guettardeae) from Papuasia

Six new species of Timonius (T. alius, T. bosaviensis, T. creber, T. cyathicalyx, T. insularis, and T. pullenii) are described from New Guinea and surrounding islands. The new species are illustrated and notes are provided on their habitat, distribution and phenology. None of the new species is readily assignable to any previously recognized subgenus or species-group.     

Preparation of Oligodeoxynucleotides Containing 6-Methylthiopurine Residues by Chemical Synthesis or Specific Methylation

Abstract

Two methods (chemical synthesis and specific methylation) are described for the preparation of oligodeoxynucleotides containing 6-methylthiopurine residues. 6-Methylthiopurine phosphoramidite (6) is prepared and incorporated into oligomers. Methylation with methyl iodide of 6-thiopurine (or 6-thioguanine) in oligonucleotides also leads to exclusive production of 6-methylthiopurine (or 6-methylthioguanine) oligomers.     

Dimeric Oligonucleotide Synthons Containing 2-Deoxy-3-O-Phosphonomethyl-α-D-erythro-pentofuranosyl Nucleosides

Abstract

The synthesis of 2′-deoxy-3′-O-phosphonomethyl-α-D-erythro-pentofuranosyl-thymine and -adenine (1, B is Thy or Ade) is described. Dimeric oligonucleotide synthons such as 2 containing isosteric phosphonate internucleoside linkage were prepared.     

Nothotalisia, a new genus of Picramniaceae from tropical America

A new genus of Picramniaceae from tropical America, Nothotalisia, is described. Of the three species in the genus, N. piranii and N. cancellata, are new to science. The third, N. peruviana, was originally described as Talisia peruviana in the Sapindaceae. The genus and all three species are described, illustrated, and distinguished by means of a key.     

Nucleic Acid Related Compounds: A Convenient Synthesis of 3-Deazauridine Analogues

Abstract

A novel synthesis of 3-deazapyrimidine glycosides utilizing pyridine-2(1H)-ones or their sodium salts and α-halomonosugars namely D-glucose or D-galactose as starting components is described.     

Papel futuro de la micafungina en el tratamiento de las micosis invasoras por hongos filamentosos

BackgroundMicafungin is a echinocandin. It inhibits β-1,3-D-glucan synthesis, thus achieving fungicidal activity against virtually all Candida spp., including those resistant to fluconazole, and fungistatic activity against Aspergillus spp., as well as several but not all pathogenic molds. Results from in vitro studies, animal models, small clinical trials, hint at possible future indications such as invasive aspergillosis and empirical viantifungal therapy, although currently there is little information published.AimsTo describe published data of micafungin as treatment against invasive mold infections, specially analysing its role in the inmunodepressed host and critical care setting.MethodsA sistematic review of literature using the principal medical search engines was performed. Terms such as micafungin, aspergillosis, zygomycosis, invasive fungal infections, emerging fungal infections, antifungal treatment or therapy, antifungal prophylaxis, empiric or pre-emptive therapy were crossed. Febrile neutropenia patients were excluded.ResultsSeveral studies in these setting were identified and were described in this review. Although there were no blinded randomized clinical trials published, treatment or prophylaxis of invasive aspergillosis and other invasive mould infections with micafungin described in open clinical studies were analyzed.ConclusionsMicafungin could play a future important role as a primary or rescue therapy, alone or in combination, in the treatment or prophylaxis of invasive fungal infections caused by moulds. New randomized clinical trials are needed to confirm their efficacy.     

Agouticarpa, a new neotropical genus of Tribe Gardenieae (Rubiaceae)

Agouticarpa, a new genus of the informalAlibertia group (Rubiaceae), is described and illustrated. It comprises six species, and occurs from Costa Rica to Bolivia. Three species are here described as new:Agouticarpa grandistipula, A. hirsuta, andA. velutina. Additionally, three new combinations are made:A. curvifolia andA. williamsii (previously inGenipa) andA. isernii (previously inAlibertia). Agouticarpa is characterized by being dioecious, having elliptic to abovate, membranaceous stipules, male flowers in a branched dichasial or thyrse-like inflorescence, a poorly developed cup-shaped calyx, pollen grains with 3–7 apertures, and large globose fruits.     

Preparation and Properties of a New Type of Acyclic,Achiral Nucleoside Analogue

Abstract

Preparation of the nucleoside analogues 1 and incorporation of 1, B = T, in deoxyribooligonucleotides by the phosphoramidite method is described. A two-step deprotection procedure was developed to reduce cleavage of the modified allylic unit. The binding properties of the modified oligonucleotides towards complementary DNA and RNA has been evaluated by T_m measurements showing a ΔT_m of ?2 to ?6.5°C per modification. An oligonucleotide with two modifications at the 3′-end showed considerable resistance towards cleavage by a 3′-exonuclease. No antiviral activity against HIV-1 or HSV-1 was found for 1, B = G or T, or for any of the trihydroxy derivatives 5.     

Review of the neotropical endemics Burmeistera, Centropogon, and Siphocampylus (Campanulaceae: Lobelioideae), with description of 18 new species and a new section

Burmeistera, Centropogon, and Siphocampylus together comprise more than 500 species endemic to the Neotropics, Current knowledge of these genera is unsatisfactory, with much diversity yet to be described. Over the past seven years, one out of every 28 specimens received for identification has represented a new species, many characterized by unique or unusual character states. Siphocampylus smilax (Bolivia) is unique in the genus in its parallelodromous leaf venation and extra-floral nectaries. Centropogon dianae (Peru) cannot be accommodated in any recognized infrageneric taxon, and a new section, Centropogon sect. Niveopsis, is proposed for it. The flowers of C. steinii (Ecuador) are the smallest known in the genus, while C. connatilobatus (Venezuela) is the first species to combine arbusculiform pubescence and connate calyx lobes. Burmeistera venezuelensis is only the second species of the genus known to occur in Venezuela and the first to be endemic; similarly, Centropogon wilburii is only the third species of Centropogon known from Mexico and the first to be endemic to that country. Additional novelties are also described.     

New and poorly known Cenozoic clown beetle compressions from France (Insecta: Coleoptera: Histeridae)

Summary

Two French fossil Histeridae are described or revised, viz. Hister cerestensis n. sp. from the Oligocene of Céreste (Lubéron) and Plegaderus pitoni (Theobald, 1935), n. comb. from the Pliocene of Chambon Lake (Puy-de-Dôme). Morphometric data are used to compare fossil and extant taxa, with multivariate statistics. A list of the fossil Histeridae is given.     

New genera and species of Jumping Ground Bugs (Hemiptera: Schizopteridae) in Dominican and Burmese amber,with a description of a meloid (Coleoptera: Meloidae) triungulin on a Burmese specimen

New genera and species of jumping ground bugs (Hemiptera: Schizopteridae) are described in Dominican and Burmese amber. In Dominican amber are described: Hypselosoma dominicana Poinar & Brown sp. n., Schizoptera dominicana Poinar sp. n. and Schizoptera hispaniolae Poinar sp. n. In Burmese amber are described: Lumatibialis burmitis Poinar gen. et sp. n. and Hexaphlebia burmanica Poinar gen. et sp. n. A triungulin attached to the dorsum of the abdomen of Lumatibialis burmitis is described as Microentomus epibatus Poinar gen. et sp. n. in the family Meloidae (Coleoptera). This specimen represents the oldest known triungulin and the first fossil phoretic association of a triungulin and hemipteran.     

An Improved Post-Synthetic Substitution Approach for Synthesis of Oligodeoxynucleotides Containing Labile 4-Substituted Thymines

Abstract

A simple procedure is described for the preparation of a versatile oligodeoxynucleotide which contains 4-phenylthiothymidine. This versatile oligomer has been successfully used for synthesis of oligonucleotides containing labile 5-methyl-N⁴, N⁴-ethanocytosine (7) or 4-azido-5-methyl-2-pyrimidinone-1-β-(2′-deoxyriboside) (8).     

The yellow-flowered species of Cuphea (Lythraceae), including three new taxa

Among the predominantly purple- and red-flowered species of the genusCuphea, only seven yellow floral tube and/or yellow-petaled members in three sections were known. We add here two new species and one new variety.Cuphea congesta from Venezuela andC. splendida var.viridiflava from Bolivia are new to sect.Melvilla.Cuphea xanthopetala from Brazil is described in sect.Euandra and expands the presence of this feature to a fourth section of the genus. A key is provided to allCuphea with yellow floral tubes and/or yellow petals to expedite determinations when these exceptional character states are present.     

Effect of the Preoperative Use of Dopamine Agonists in the Postoperative Course of Prolactinomas: A Systematic Review

ObjectiveSince the 1980s, it has been discussed whether the preoperative treatment of prolactinomas with dopamine agonists (DAs) is beneficial or detrimental regarding postoperative residue or recurrence. Many neurosurgeons have emphasized the difficulties caused by fibrosis during the ablation of such prolactinomas.MethodsFrom February to December 2012, the authors searched electronic databases and book chapters published from 1991 to 2012; a total of 3,771 articles and 37 book chapters were searched. Ten articles that explicitly addressed this issue were identified.ResultsFive articles reported that preoperative treatment did not affect postoperative status. One article described a positive influence of preoperative treatment with DAs (P < .01), and 3 articles found a negative influence (P = .040, P = .02, no significance value reported). One article described histopathological evidence of tumor fibrosis that was found intraoperatively after preoperative DA treatment.ConclusionsThis systematic review did not identify any strong evidence that preoperative treatment of prolactinomas with DAs is harmful or beneficial. Therefore, further studies are needed. (Endocr Pract. 2014;20:70-74)     

Synthesis of 2′,3′-Didehydro-2′,3′-dideoxyisoinosine and Oxidation of Fluorescent 2-Hydroxypurine Nucleosides by Xanthine Oxidase

Abstract

The syntheses of 2′,3′-didehydro-2′,3′-dideoxyisoinosine (d4isoI, 4) as well as 7-deaza-2′,3′-didehydro-2′,3′-dideoxyisoinosine (d4c₇isoI, 5) are described. Compounds 4 and 5 show both strong fluorescence. Compound 4 is oxidized by xanthine oxidase to give the corresponding xanthine 2′,3′-dideoxy-2′,3′-didehydronucleosides. A preparative chemo-enzymatic synthesis of 2′-deoxyxanthosine (3) is described.