α-Hydroxyphosphonate Oligonucleotides: A Promising DNA Type?

Abstract

The synthesis of monomers ( S )-1, ( R )-1 and 2 derived from (5′ S )-, (5′ R )-2′-deoxythymidine-5′-C-phosphonic acids and 2′,5′-dideoxythymidine-5′-C-phosphonic acids was elaborated. The protection of the 5′-hydroxyl by the methoxycarbonyl group was a key step of the synthesis. Prepared monomers were used for the solid-phase assembly of several types oligothymidylate 15-mers ( S )-3, ( S )-4, ( S )-5, ( R )-4 and ( R )-5 containing the chiral 3′-O-P-CH(OH)-5″ internucleotide linkage. Their hybridization properties with dA₁₅ and rA₁₅ were studied as well as their resistance against nuclease cleavage.     

New triterpene oligoglycosides from the Caribbean sponge Erylus formosus

Seven new triterpene glycosides, erylosides R₁ (1), T₁ (3), T₂ (4), T₃ (5), T₄ (6), T₅ (7), and T₆ (8) along with the known formoside (2) were isolated from the sponge Erylus formosus collected along the Caribbean coast of Mexico. Glycoside 1 was determined as a trisaccharide, glycoside 2 as a tetrasaccharide while glycosides 3–8 were hexasaccharide. Their carbohydrate chains were unprecedented and have never been found in oligosaccharides from other biological sources, except Erylus spp. Three carbohydrate chains in the glycosides 3 and 6, 4 and 7, 5 and 8 correspondingly are new. The glycosides 1–5 have penasterol as aglycone while glycosides 6–8 proved to be glycoconjugates of 24-methylene-14-carboxy-lanost-8(9)-en-3β-ol.     

Synthesis of the Fluoromethyl Derivatives of Carbocyclic Oxetanocin A

Abstract

Treatment of the 2,3-di-O-benzoate 1 with sodium boronhydride mainly afforded the 3-O-benzoate 2 accompanied with isomers 3a,b and fully deprotected product 4. Compound 2 was converted to 5, from which 8 was obtained. The 1-cyclobutanols 8 and 5 were successfully condensed with 6-chloropurine by Mitsunobu reaction to give 9 and 11, respectively. After partial deprotection, the cyclobutyl nucleosides 10 and 15 were subjected to fluorination using DAST to afford the fluoromethyl analogs 12 and 16 from which target compounds 14 and 17 were obtained in good yields, respectively.

     

海南石斛化学成分研究

为了解海南石斛(Dendrobium hainanense Rolfe)的化学成分,采用色谱技术从海南石斛茎叶中分离得到14个化合物,经波谱分析分别鉴定为:2,6-二甲氧基对苯醌(1)、(+)-dehydrovomifoliol(2)、blumenol A(3)、2,7-二羟基-3,4-二甲氧基-9,10-二氢菲(4)、2,7-二羟基-3,4-二甲氧基菲(5)、3,7-二羟基-2,4-二甲氧基菲(6)、3-羟基-2,4,7-三甲氧基-9,10-二氢菲(7)、3-羟基-2,4,7-三甲氧基菲(8)、3,4,7-三羟基-2-甲氧基菲(9)、3,7-二羟基-2,4-二甲氧基-9,10-二氢菲(10)、(+)-lyoniresinol(11)、丁香脂素(12)、denchrysan A(13)和nobilone(14)。这些化合物均为首次从海南石斛中分离得到。活性测试结果表明化合物4~6、8~9、11和14对乙酰胆碱酯酶有抑制活性。     

Study of reactivity of cyanoacetohydrazonoethyl-N-ethyl-N-methyl benzenesulfonamide: preparation of novel anticancer and antimicrobial active heterocyclic benzenesulfonamide derivatives and their molecular docking against dihydrofolate reductase

Abstract

This article describes the synthesis of some novel heterocyclic sulfonamides having biologically active thiophene 3, 4, 5, 6, coumarin 8, benzocoumarin 9, thiazole 7, piperidine 10, pyrrolidine 11, pyrazole 14 and pyridine 12, 13. Starting with 4-(1-(2-(2-cyanoacetyl)hydrazono)ethyl)-N-ethyl-N-methylbenzenesulfonamide (2), which was prepared from condensation of acetophenone derivative 1 with 2-cyanoacetohydrazide. The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, ¹H NMR, ¹³C NMR, ¹⁹F NMR and MS spectral data. All the newly synthesized heterocyclic sulfonamides were evaluated as in-vitro anti-breast cancer cell line (MCF7) and as in-vitro antimicrobial agents. Compounds 8, 5 and 11 were more active than MTX reference drug and compounds 12, 7, 4, 14, 5 and 8 were highly potent against Klebsiella pneumonia. Molecular operating environment performed virtual screening using molecular docking studies of the synthesized compounds. The results indicated that some prepared compounds are suitable inhibitor against dihydrofolate reductase (DHFR) enzyme (PDBSD:4DFR) with further modification.     

Synthesis and antioxidant,cytotoxicity and antimicrobial activities of novel curcumin mimics

Claisen-Schmidt condensation of 3-(1,2,3,6-tetrahydro-1-methylpyridin-4-yl)-2,4,5- trimethoxybenzaldehyde 3 and various aromatic, heterocyclic and alicyclic amides of 3- aminoacetophenone 6(a–s) afforded novel curcumin mimics. All the synthesized compounds were characterized by IR, ¹H NMR, Mass spectroscopy and evaluated for antioxidant, cytotoxicity and antimicrobial activity. Out of the 20 compounds screened, compounds 7i, 7l, 7q, and 7n have shown excellent radical scavenging activity, compounds 7o, 7t, 7f, and 7r have shown significant xanthine oxidase inhibition, and compounds 7a, 7k and 7l were found to be potent inhibitors of selected cancer cell lines. Compounds 7h, 7t, 7l, 7i, and 7e have shown good antibacterial activity, whereas compounds 7j, 7f, 7o, 7h, and 7t exhibited significant antifungal activity.     

Synthesis of Acyclovir and HBG Analogues Having Nicotinonitrile and Its 2-methyloxy 1,2,3-triazole

Reaction of pyridin-2(1H)-one 1 with 4-bromobutylacetate (2), (2-acetoxyethoxy)methyl bromide (3) gave the corresponding nicotinonitrile O-acyclonucleosides, 4 and 5, respectively. Deacetylation of 4 and 5 gave the corresponding deprotected acyclonucleosides 6 and 7, respectively. Treatment of pyridin-2(1H)-one 1 with 1,3-dichloropropan-2-ol (8), epichlorohydrin (10) and allyl bromide (12) gave the corresponding nicotinonitrile O-acyclonucleosides 9, 11, and 13, respectively. Furthermore, reaction of pyridin-2(1H)-one 1 with the propargyl bromide (14) gave the corresponding 2-O-propargyl derivative 15, which was reacted via [3+2] cycloaddition with 4-azidobutyl acetate (16) and [(2-acetoxyethoxy)methyl]azide (17) to give the corresponding 1,2,3-triazole derivatives 18 and 19, respectively. The structures of the new synthesized compounds were characterized by using IR, ¹H, ¹³C NMR spectra, and microanalysis. Selected members of these compounds were screened for antibacterial activity.     

Synthesis and Antimicrobial Activity of Some S-β-D-Glucosides of 4-Mercaptopyrimidine

5-Acetyl-2-aryl-6-methyl-4-(2,3,4,6-tetra- O -acetyl-β-D-glucopyranosylmercapto)pyramidines 3a–c were obtained by the reaction of 5-acetyl-2-aryl-6-methyl-pyrimidine thiol 1a–c with 2,3,4,6-tetra- O -acetyl-α-D-glucopyranosyl bromide (2) in aq. KOH/acetone. The reaction of 1a–c with peracetylated galactose 5 and peracetylated ribose 8 under MW irradiation gave 5-acetyl-2-aryl-6-methyl-4-(2,3,4,6-tetra- O -acetyl-β-D-galactopyranosylmercapto)pyrimidine 6a–c and 5-acetyl-2-aryl-6-methyl-4-(2,3,5-tri- O -acetyl-β-D-ribofuranosylmercapto)pyrimidines 9a–c. The deprotection of 3a–c, 6a–c, and 9a–c in the presence of methanol and TEA/H₂O yielded the deprotected products 4a–c, 7a–c, and 10a–c. The structures of the compounds were confirmed by using IR, ¹H, ¹³C spectra and microanalysis. Selected members of these compounds were screened for antimicrobial activity.     

<Emphasis Type="Italic">Alansmia</Emphasis>, a new genus of grammitid ferns (Polypodiaceae) segregated from <Emphasis Type="Italic">Terpsichore</Emphasis>

Alansmia, a new genus of grammitid ferns is described and combinations are made for the 26 species known to belong to it. Alansmia is supported by five morphological synapomorphies: setae present on the rhizomes, cells of the rhizome scales turgid, both surfaces of the rhizome scales ciliate, laminae membranaceous, and sporangial capsules setose. Other diagnostic characters include pendent fronds with indeterminate growth, concolorous, orange to castaneous rhizome scales with ciliate or sometimes glandular margins, hydathodes often cretaceous, and setae simple, paired or stellate. The group also exhibits the uncommon characteristic of producing both trilete and apparently monolete spores, sometimes on the same plant. New combinations are made for Alansmia alfaroi, A. bradeana, A. canescens, A. concinna, A. contacta, A. cultrata, A. dependens, A. diaphana, A. elastica, A. glandulifera, A. heteromorpha, A. immixta, A. kirkii, A. lanigera, A. laxa, A. longa, A. monosora, A. reclinata, A. semilunaris, A. senilis, A. smithii, A. spathulata, A. stella var. stella, A. stella var. flava, A. turrialbae, A. variabilis, A. xanthotrichia. Lectotypifications are made for Alansmia concina, A. variabilis, Polypodium ciliare, P. flexile, and P. ovalescens. The genus is named in honor of pteridologist Alan R. Smith.     

Synthesis Of 2,2,3-Tris(Hydroxymethyl)Methylenecyclopropane Analogues Of Nucleosides

Synthesis of 2,2,3-tris(hydroxymethyl)methylenecyclopropane analogues 16a, 16b, 17a, and 17b is described. Diethyl ester of Feist's acid 18b was hydroxymethylated via carbanion formation using formaldehyde under simultaneous isomerization to cis diester to give intermediate 19. Reduction followed by acetylation gave triacetate 22. Addition of bromine afforded reagent 23, which was used for alkylation-elimination of adenine and 2-amino-6-chloropurine to provide Z,E-isomeric mixtures of 24a and 24b. Deacetylation and separation furnished the Z-isomers 16a, 16c and E-isomers 17a, 17c. Hydrolytic dechlorination of 16c and 17c gave guanine analogues 16b and 17b. None of the analogues exhibited a significant antiviral activity. Adenosine deaminase is refractory toward adenine analogues 16a and 17a.     

Plant regeneration from protoplasts ofCapsicum annuum L. cv. California Wonder

Plant regeneration from mesophyll protoplasts of pepper,Capsicum annuum L. cv. California Wonder has been demonstrated via shoot organogenesis. Protoplasts isolated from fully expanded leaves of 3-week-old axenic shoots when cultured in TM medium supplemented with 1 mg l ⁻¹ NAA, 1 mg l ⁻¹ 2,4-D, 0 5 mg l ⁻¹ BAP (CM 1) resulted in divisions with a frequency ranging from 20–25 %. Antioxidant ascorbic acid and polyvinylpyrrolidone (PVP) in the medium and incubation in the dark helped overcome browning of protoplasts. Microcalli and macrocalli were formed in TM medium containing 2 mg l ⁻¹ NAA and 0.5 mg l ⁻¹ BAP (CM II) and MS gelled medium containing 2 mg 1 ⁻¹ NAA and 0 5 mg 1 ⁻¹ BAP (CM III), respectively. Regeneration of plantlets was possible via caulogenesis. Microshoots, 2–5 percallus appeared on MS gelled medium enriched with 0.5 mg l ⁻¹ IAA, 2mg l ⁻¹ GA and l0mg l ⁻¹ BAP (CM IVc). Rooting of microshoots was obtained on half strength gelled medium containing 1 mg l ⁻¹ NAA and 0.5mg l ⁻¹ BAP. Protoplasts isolated from cotyledons failed to divide and degenerated eventually.     

Stenogrammitis, a new genus of grammitid ferns segregated from Lellingeria (Polypodiaceae)

Stenogrammitis , a new genus of grammitid ferns, is segregated from Lellingeria based on morphological and molecular evidence. It differs from Lellingeria by linear leaves usually less than 5 mm wide, clathrate iridescent rhizome scales that are glabrous except for a single apical cilium, veins unbranched and only one per segment, fertile veins usually with the dark sclerenchyma visible beneath the sporangia, and x = 33. In contrast, Lellingeria has broader laminae, veins pinnate within the segments, and fertile veins not visible beneath the sporangia. Melpomene, which is sister to Stenogrammitis and Lellingeria, differs from those two genera by reddish setae on the leaves and rhizome scales papillate at the apex. Some species of Stenogrammitis are also distinctive by hemidimorphic laminae that have the fertile portion less dissected than the sterile. Stenogrammitis is pantropical and currently comprises 24 species, 12 of which occur in the Neotropics, six in Africa, four in Madagascar, and two on Pacific Islands. New combinations are made for Stenogrammitis aethiopica, S. anamorphosa, S. ascensionensis, S. boivinii, S. delitescens, S. jamesonii, S. hartii, S. hellwigii, S. hildebrandtii, S. limula, S. luetzelburgii, S. myosuroides, S. nutata, S. oosora, S. paucipinnata, S. prionodes, S. pumila, S. ruglessii, S. rupestris, S. saffordii, S. strangeana, S. tomensis, S. subcoriacea, and S. wittigiana. Lectotypifications are made for Grammitis muscosa, Polypodium itatiayense, P. oosorum var. micropecten, P. serrulatum forma major, P. serrulatum forma minor, S. luetzelburgii, S. myosuroides, and S. wittigiana. Illustrations are presented for the diagnostic characters of the genus, as well as a map with the geographical distribution.     

Soil–Methanogen Interactions in Two Peatlands (Bog,Fen) in Central New York State

Rates of methanogenesis vary widely in peat soils, yet the reasons are poorly known. We examined rates of methanogenesis and methanogen diversity in relation to soil chemical and biological characteristics in 2 peatlands in New York State. One was an acidic (pH < 4.5) bog dominated by Sphagnum mosses and ericaceous shrubs, although deeper peat was derived from sedges. The other was a fen dominated by Carex lacustris sedges with near-neutral pH soil. At both sites, the most active rates of methanogenesis occurred in the top 20 cm of the peat profile, even when using a substrate-induced methanogenesis technique with added glucose that stimulated rates up to 2 μ mol g ^{? 1} day ^?1 in the bog and 6 μ mol g ^?1 day ^?1 in the fen. Rates of anaerobic CO ₂ production were greater in the bog (0–36 μ mol g ^?1 day ^?1 ) than in the fen (0–5 μ mol g ^?1 day ^?1 ), and added glucose induced greater rates in the sedge-derived peat from the bog than the fen. The peat soil was much more decomposed throughout the profile in the fen. Analysis of chemical elements in the peat profile revealed a striking anomaly: a very high concentration of Pb in surface peat of the bog, which might have constrained methanogenesis. Application of T-RFLP analysis to methanogens revealed dominance by a Methanomicrobiales E2 clade of H ₂ /CO ₂ users in the acidic peat soil of the bog, whereas deeper peat had a different Methanomicrobiales E1 clade, uncultured euryarchaeal rice cluster (RC)-I and RC-II groups, marine benthic group D (MBD) and a new cluster called subaqueous cluster (SC). In contrast, T-RFLP analysis of peat from the fen revealed co-dominance by Methanosaetaceae and Methanomicrobiales E1. The results showed complex relationships between rates of methanogenesis, methanogen populations and metabolic substrate availability with idiosyncratic interactions of trace chemical elements.     

薏苡糠壳的化学成分及其种子萌发活性研究

为了解薏苡(Coixlachryma-jobi)糠壳的化学成分,利用多种柱色谱技术对其乙醇提取物乙酸乙酯萃取部位进行分离,经波谱数据分析鉴定了15个化合物,分别为香豆酸(1)、香豆酸甲酯(2)、2-羟乙基-香豆酸酯(3)、咖啡酸甲酯(4)、阿魏酸甲酯(5)、(E)-3-(4-甲氧基苯基)丙烯酸(6)、2,3-二羟基-1-(4-羟基-3-甲氧基苯基)-1-丙酮(7)、2,3-二羟基-1-(4-羟基-3,5-二甲氧基苯基)-1-丙酮(8)、对羟基苯甲酸(9)、3-羟基-4-甲氧基苯甲酸(10)、1,3,5-三甲氧基苯(11)、methyl (3-hydroxy-2-oxo-2,3-dihydroindol-3-yl)-acetate (12)、尿囊素(13)、2-(2-羟乙基)-3-甲基反丁烯二酸(14)和油酸(15),其中化合物3、7、12、13和14为首次从薏苡中分离得到。活性测试结果表明,化合物1、2、9、10和11对种子萌发具有较强的抑制作用。     

Synthesis and Antiviral Activity of 1,5-and 1,3-Dialkyl-1,2,4-triazole C-Nucleosides Derived from 1-(Chloroalkyl)-1-aza-2-azoniaallene Salts

Abstract

Reactions of α, α′-dichloroazo compounds 2 with SbCl₅ gave 1-(chloroalkyl)-1-aza-2-azoniaallene salts 3 as reactive intermediates. Cycloadditions of 3 with the ribofuranosyl cyanide 4 afforded the β-D-ribofuranosyl-1,2,4-triazolium salts 5, which rearranged spontaneously to salts 6. Hydrolysis of 6 gave the 1,2,4-triazole C-nucleosides 7, which yielded the free nucleosides 8 after deblocking. Analogously, 12 was prepared from the cycloaddition of 4 with the α-chloroazo compound 10 in the presence of SbCl₅. Deblocking of 12 with sodium methoxide afforded 13. Compounds 8a,b,e,f and 13 were tested against HIV-1, HIV-2, HSV-1 and HSV-2 and were found to be inactive.     

油榄仁果实化学成分的研究

为了解油榄仁(Terminalia bellirica Roxb.)的化学成分,从油榄仁果实的乙酸乙酯提取物中分离得到11个化合物,通过波谱分析,分别鉴定为:表松脂酚(1)、(–)-芝麻素(2)、麻醉椒苦素(3)、二氢醉椒素(4)、异香兰素(5)、3,4-二羟基苯甲酸(6)、没食子酸(7)、没食子酸甲酯(8)、没食子酸乙酯(9)、3,4,8,9,10-五羟基二苯骈[b,d]吡喃-6-酮(10)、polystachyol(11),其中化合物1~6、10和11为首次从油榄仁果实中分离得到。     

Evaluation of novel <Superscript>99m</Superscript>Tc(I)-labeled homobivalent α-melanocyte-stimulating hormone analogs for melanocortin-1 receptor targeting

Abstract  

Aiming to apply the multivalency concept to melanoma imaging, we have assessed the in vivo melanocortin type 1 receptor (MC1R)-targeting properties of ^99mTc(I)-labeled homobivalent peptide conjugates which contain copies of the α-melanocyte-stimulating hormone (α-MSH) analog [Ac-Nle⁴, Asp⁵, d-Phe⁷, Lys¹¹]α-MSH_4–11 separated by linkers of different length (L ² nine atoms and L ³ 14 atoms). The MC1R-binding affinity of L ² and L ³ is significantly higher than that of the monovalent conjugate L ¹ . Metallation of these conjugates yielded the complexes fac-[M(CO)₃(k³-L)]⁺ (M is ^99mTc/Re; 1/1a, L is L ¹ ; 2/2a, L is L ² ; 3/3a, L is L ³ ), with IC₅₀ values in the subnanomolar and nanomolar range. The MC1R-mediated internalization of 2 and 3 is higher than that of 1 in B16F1 melanoma cells. Biodistribution studies in melanoma-bearing mice have shown low nonspecific accumulation with a tumor uptake that correlates with IC₅₀ values. However, no correlation between tumor uptake and valency was found. Nevertheless, 2 displayed the highest tumor retention, and the best tumor to nontarget organ ratios.     

Synthesis of new N,N′-bis[1-aryl-3-(piperidine-1-yl)propylidene]hydrazine dihydrochlorides and evaluation of their cytotoxicity against human hepatoma and breast cancer cells

Abstract

N,N′-Bis[1-aryl-3-(piperidine-1-yl)propylidene]hydrazine dihydrochlorides were synthesized by the reaction of 2 mols of 1-aryl-3-(piperidine-1-yl)-1-propanone hydrochlorides with 1?mol of hydrazine hydrate. Aryl part was C₆H₅ (P1), 4-CH₃C₆H₄ (P2), 4-CH₃OC₆H₄ (P3), 4-HOC₆H₄ (P4), 4-ClC₆H₄ (P5), 3-CH₃OC₆H₄ (P6), 4-FC₆H₄ (P7) and 4-BrC₆H₄ (P8). Except P1, all compounds were reported for the first time. The chemical structures were confirmed by UV, ¹H NMR, ¹³C NMR and HRMS spectra. P1, P2, P7 and P8 against human hepatoma (Huh7) cells and P1, P2, P4, P5, P6, P7 and P8 against breast cancer (T47D) cells have shown cytotoxicity. P1, P2 and P7 had more potent cytotoxicity against Huh7 cells than the reference compound 5-FU, whereas only P2 was more potent than the 5-FU against T47D cells. Representative compound P7 inhibited the mitochondrial respiration at 144, 264 and 424?µM concentrations dose-dependantly in liver homogenates. The results suggest that P1, P2, P7 and P8 may serve as model compounds for further synthetic studies.     

Synthesis and Reactions of Some Glycosylamine Derivatives of 6-Azauracil Nucleosides

Abstract

Reaction of the silylated 6-azauracil (2) with 2-acetamido-1,3,4,6-tetra-O-acetyl-2-deoxy-D-glucose (3) gave 1-(2-acetamido-3,4,6-tri-O-acetyl-2-deoxy-ß-D-glucopyranosyl)-6-azauracil (4), which gave the free nucleoside 5 on deblocking. Acetalation of 5 gave the monoacetal 6 which was oxidized into the ketone 7. Reduction of 7 gave the allo-nucleoside 9 which on hydrolysis afforded the free nucleoside 10. Alternatively, compound 10 was obtained from mesylation of 6 to give 8 followed by subsequent acetolysis and hydrolysis.