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An efficient environmentally benign route for the synthesis of benzimidazo[2,1-a]isoquinoline has been developed by reacting 2-ethynylbenzaldehyde and related substituted alkynylbenzaldehydes with variously substituted ortho-phenylenediamines and aliphatic amines in ethanol. This method provides a convenient, room temperature, atom-economical, and catalyst-free access to diversely substituted isoquinoline fused benzimidazoles. Regioselectivity of the reaction, as referred to o-phenylenediamines, was confirmed by X-ray crystallography. The reaction was found to occur in three major steps (imine formations, cyclization, and aromatization) and a mechanism has been proposed.

A novel methodology to access alkynyl nucleoside analogs was elaborated. Highly fluorescent 5-alkynylfuropyrimidines were synthesized (97-46%) and their antiviral properties investigated in vitro. Regiochemistry of the functionalization was achieved with the aid of 5-endo-dig electrophilic halocyclization of acetyl 5-p-tolyl- or 5-p-pentylphenyl-2'-deoxyuridine. Structure of one of the resulting nucleosides, 6-p-tolyl-5-iodo-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-one, was confirmed by X-ray crystallography, and its conformation was compared to related nucleosides. Diverse alkynyl substituents were introduced at the heterobicyclic base C-5 position via Sonogashira coupling of 5-iodo-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-ones. The resulting compounds had fluorescence emissions of 452 to 481 nm. High quantum yields of 0.53-0.60 were observed for 9-ethynyl-9-fluorenol and propargyl alcohol/methyl ether-modified furopyrimidines. These modified nucleosides, designed in the form of ribose acetyl esters, represent potential tools for fluorescent tagging, studying nucleoside metabolism, 2′-deoxyribonucleoside kinase activity, and antiviral activity. Antiviral assays against a broad spectrum of DNA and RNA viruses showed that in human embryonic lung (HEL) cell cultures some of the compounds showed antiviral activity (EC50 1.3-13.2 μM) against varicella-zoster virus (VZV). The alkynyl furopyrimidine with two p-pentylphenyl substituents emerged as the best compound with reasonable and selective anti-VZV activity, confirming p-pentylphenyl potency as a pharmacophore., Graphical abstract Novel fluorescent nucleoside analogs, 5-alkynylfuropyrimidines show high quantum yields (0.53-0.60). Assays in VZV cell cultures are presented.Image 1, Highlights • A new synthetic protocol was established to access novel class of nucleosides, 6-alkynyl furopyrimidines. • Antiviral activity (EC50 1.3-13.2 μM) in human embryonic lung (HEL) cell cultures against varicella-zoster virus (VZV); inhibition against TK- VZV strain exceeded that of acyclovir. • Emission wavelength values 453-481 nm (λex = 360 nm) were observed for 6-alkynyl furopyrimidines. • High quantum yields (0.53-0.60) observed for selected compounds. • X-ray crystallography confirmed structure of 6-p-tolyl-5-iodo-2'-deoxyribofuranosyl-furo[2,3-d]pyrimidin-2-one.

The directionality of the hole-transfer processes between DNA backbone and base was investigated by using phosphorodithioate [P(S- )=S] components. ESR spectroscopy in homogeneous frozen aqueous solutions and pulse radiolysis in aqueous solution at ambient temperature confirmed initial formation of G.+ -P(S- )=S. The ionization potential of G-P(S- )=S was calculated to be slightly lower than that of guanine in 5'-dGMP. Subsequent thermally activated hole transfer from G.+ to P(S- )=S led to dithiyl radical (P-2S. ) formation on the μs timescale. In parallel, ESR spectroscopy, pulse radiolysis, and density functional theory (DFT) calculations confirmed P-2S. formation in an abasic phosphorodithioate model compound. ESR investigations at low temperatures and higher G-P(S- )=S concentrations showed a bimolecular conversion of P-2S. to the σ2 -σ*1 -bonded dimer anion radical [-P-2S - . 2S-P-]- [ΔG (150 K, DFT)=-7.2 kcal mol-1 ]. However, [-P-2S - . 2S-P-]- formation was not observed by pulse radiolysis [ΔG° (298 K, DFT)=-1.4 kcal mol-1 ]. Neither P-2S. nor [-P-2S - . 2S-P-]- oxidized guanine base; only base-to-backbone hole transfer occurs in phosphorodithioate.

Reactions of dicobalt octacarbonyl [Co2(CO)8] with 2′‐deoxy‐5‐oxopropynyluridines and related compounds gave dicobalt hexacarbonyl nucleoside complexes (83–31 %). The synthetic outcomes were confirmed by X‐ray structure determination of dicobalt hexacarbonyl 2′‐deoxy‐5‐(4‐hydroxybut‐1‐yn‐1‐yl)uridine, which exhibits intermolecular hydrogen bonding between a modified base and ribose. The electronic structure of this compound was characterized by the DFT calculations. The growth inhibition of HeLa and K562 cancer cell lines by organometallic nucleosides was examined and compared to that by alkynyl nucleoside precursors. Coordination of the dicobalt carbonyl moiety to the 2′‐deoxy‐5‐alkynyluridines led to a significant increase in the cytotoxic potency. The cobalt compounds displayed antiproliferative activities with median inhibitory values (IC50) in the range of 20 to 80 μm for the HeLa cell line and 18 to 30 μm for the K562 cell line. Coordination of an acetyl‐substituted cobalt nucleoside was expanded by using the 1,1‐bis(diphenylphosphino)methane (dppm) ligand, which exhibited cytotoxicity at comparable levels. The formation of reactive oxygen species in the presence of cobalt compounds was determined in K562 cells. The results indicate that the mechanism of action for most antiproliferative cobalt compounds may be related to the induction of oxidative stress.

In continuation of synthetic pursuit of metallo-nucleosides, in particular dicobalt hexacarbonyl 5-alkynyl-2′-deoxyuridines, novel compounds with alkynyl groups were synthesized, starting from 5-iodo-2′-deoxyuridine. Reactions of dicobalt octacarbonyl [Co2(CO)8] with 2′-deoxy-5-oxopropynyluridines and related compounds gave dicobalt hexacarbonyl nucleoside complexes (83–31%). The growth inhibition of HeLa and K562 cancer cell lines by organometallic nucleosides was examined and compared to that by alkynyl nucleoside precursors. Coordination of the dicobalt carbonyl moiety to the 2′-deoxy-5-alkynyluridines led to a significant increase in its cytotoxic potency. The cobalt compounds antiproliferative activities against the HeLa cell line and the K562 cell line will be described. Coordination of an acetyl-substituted cobalt nucleoside was expanded using the 1,1-bis(diphenylphosphino)methane (dppm) ligand, resulting in cytotoxicity at comparable levels. The formation of reactive oxygen species in the presence of cobalt compounds was determined in K562 cells. The results indicate that the mechanism of action for most antiproliferative cobalt compounds may be related to the induction of oxidative stress.

The reaction of alk-3-yn-1-ones (a bifunctional reagent) with o-phenylenediamines provides an effective synthetic method with high atom economy for the preparation of diversely substituted 1,5-3H-benzodiazepines. The reaction initially leads to the formation of conjugated enaminones (3-amino-2-alkenones, 51–99%), at room temperature, which constitutes a formal non-catalyzed hydroamination of the non-conjugated alkyne. Non-symmetrical o-phenylenediamines react in a regioselective fashion with respect to amino groups. Both the direct microwave-accelerated reaction of o-phenylenediamines with alkynones in ethanol and the intramolecular cyclization of intermediate enaminones in ethanol/acetic acid lead to substituted 1,5-benzodiazepines with good yields (39–92 and 26–99%). The regio- and stereochemical outcomes of these processes are confirmed by the X-ray structure determination of (Z)-3-[(2-amino-4-methylanilino)-4-(4-methylphenyl)-1-phenylbut-2-en-1-one], 4-[(4-methylphenyl)methyl]-7-nitro-2-phenyl-3H-1,5-benzodiazepine and 6,8-dimethyl-4-(4-methylbenzyl)-2-phenyl-3H-benzo[b][1,5]diazepine.

A 5-endo-dig halocyclization of 2-fluoroalk-3-yn-1-ones with the use of N-iodo- and N-bromosuccinimide, in the presence of gold chloride/zinc bromide (5:20 mol-%, dichloromethane), under ambient conditions, provides a facile method for the synthesis of 2,5-disubstituted 3-bromo-4-fluoro- and 3-fluoro-4-iodofurans. The sequential procedure starts at monofluorination of the alk-1-en-3-yn-1-yl silyl ethers with Selectfluor and proceeds with good overall yields (62-78%).

Fluorination of 1,4-disubstituted tert-butyldimethylsilyl but-1-en-3-yn-1-yl ethers with Selectfluor gives 2-mono-fluorobut-3-yn-1-ones. Subsequent 5-endo-dig cyclization in the presence of chlorotriphenylphosphine gold(I)/silver trifluoromethanesulfonate (both 5 mol%, dichloromethane) under ambient conditions, provides a facile method for the generation of mainly 2,5-diaryl-substituted 3-fluorofurans in high yields (89―96%). The structure of 2-(4-bromophenyl)-3-fluoro-5-(4-methylphenyl)furan was confirmed by X-ray crystallography.

Sonogashira coupling of diacetyl 5-ethynyl-2′-deoxyuridine with diacetyl 5-iodo-2′-deoxyuridine gave the acylated ethynediyl-linked 2′-deoxyuridine dimer (3 b; 63 %), which was deprotected with ammonia/methanol to give ethynediyl-linked 2′-deoxyuridines (3 a; 79 %). Treatment of 5-ethynyl-2′-deoxyuridine (1 a) with 5-iodo-2′-deoxyuridine gave the furopyrimidine linked to 2′-deoxyuridine (78 %). Catalytic oxidative coupling of 1 a (O2, CuI, Pd/C, N,N-dimethylformamide) gave butadiynediyl-linked 2′-deoxyuridines (4; 84 %). Double Sonogashira coupling of 5-iodo-2′-deoxyuridine with 1,4-diethynylbenzene gave 1,4-phenylenediethynediyl-bridged 2′-deoxyuridines (5; 83 %). Cu-catalyzed cycloisomerization of dimers 4 and 5 gave their furopyrimidine derivatives. One-electron addition to 1 a, 3 a, and 4 gave the anion radical, the EPR spectra of which showed that the unpaired electron is largely localized at C6 of one uracil ring (17 G doublet) at 77 K. The EPR spectra of the one-electron-oxidized derivatives of ethynediyl- and butadiynediyl-linked uridines 3 a and 4 at 77 K showed that the unpaired electron is delocalized over both rings. Therefore, structures 3 a and 4 provide an efficient electronic link for hole conduction between the uracil rings. However, for the excess electron, an activation barrier prevents coupling to both rings. These dimeric structures could provide a gate that would separate hole transfer from electron transport between strands in DNA systems. In the crystal structure of acylated dimer 3 b, the bases were found in the anti position relative to each other across the ethynyl link, and similar anti conformation was preserved in the derived furopyrimidine–deoxyuridine dinucleoside.

Ligand-free 5-endo-dig cyclization of 1,4- and 1,2,4-substituted but-3-yn-1-yl (homopropargyl) azides in the presence of zinc chloride (usually 20 mol %) in dichloroethane at elevated temperature provides 2,5-di- and 2,3,5-trisubstituted pyrroles in high to moderate yields (91–41%). Both conventional and microwave protocols furnished comparable results. A structure of 2-(4-fluorophenyl)-5-(4-methylphenyl)-1H-pyrrole was confirmed by X-ray crystallography.

The 5-endo-dig chlorocyclization of 1,4-disubstituted alk-3-yn-1-ones (propargylic ketones) with the use of trichloro-s-triazinetrione (trichloroisocyanuric acid, TCCA; 0.4 equiv.) in toluene, at room temperature, in the absence of base, provides 2,5-disubstituted 3-chlorofurans in high yields (79–96 %). The reaction can be accomplished by using commercially available swimming pool sanitizer. Selected 3-chlorofuran was validated as a substrate for Suzuki–Miyaura coupling. In a similar manner, chlorocyclization of 5-alkynyl-2′-deoxyuridines produces 5-chlorofuropyrimidine nucleosides (76–83 %), which are analogues of potent anitviral agents. (© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

The synthesis of Ag(CNAr)2BF4, Ag(CNAr)2NO3, AuCl(CNAr), CuCl(CNAr), [CuCl(CNAr)2]2, Fe(CO)4CNAr, trans-[PdI2(CNAr)2], and trans-[PtI2(CNAr)2] complexes containing the fluorous isocyanide ligand CNAr [Ar = 4-F(CF2)8(CH2)4OC6H4] and the examination of the mesomorphic properties of these novel fluorous organometallics are reported. The fluorous isocyanide ligand is mesomorphic, as opposed to its hydrocarbon analogue. In general, the fluorophobic effect enhances the microsegregation in the investigated organometallic/isocyanide complexes, as compared to their hydrocarbon analogues. The fluorous mesophases are stable over a wider temperature range and exhibit higher transition temperatures.(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Reactions of 5-alkynyl-2'-deoxyuridines with dicobalt octacarbonyl Co2(CO)8 in THF at room temperature gave hexacarbonyl dicobalt nucleoside complexes (77-93%). The metallo-nucleosides were characterized, including an X-ray structure of a 1-cyclohexanol derivative. In crystalline form, the Co-Co bond is perpendicular to the plane of the uracil base, which is found in the anti position. The level of growth inhibition of MCF-7 and MDA-MB-231 human breast cancer cell lines was examined and compared to results obtained with the alkynyl nucleoside precursors. The cobalt compounds displayed good antiproliferative activities with IC50 values in the range of 5-50 microM. Interestingly, the coordination of the dicobalt carbonyl moiety to 5-alkynyl-2'-deoxyuridines led to a significant increase in the cytotoxic potency for alkyl/aryl substituents at the non-nucleoside side of the alkyne, but in the case of hydrogen (terminal alkyne) or a silyl group, a decrease of the cytotoxic effect was observed. As demonstrated using examples for an active and a low active target compound, the cytotoxicity was significantly influenced by the uptake into the tumor cells and the biodistribution into the nuclei.

[structure: see text]. 5-Endo-dig cycloisomerization of 1,4-di- and 1,2,4-trisubstituted but-3-yn-1-ones in the presence of a catalytic amount of zinc chloride (10 mol %) in dichloromethane at room temperature (22 degrees C) provides 2,5-di- and 2,3,5-trisubstituted furans in high yields (85-97%).

[reaction: see text] Thionation of amides, 1,4-diketones, N-(2-oxoalkyl)amides, N,N'-acylhydrazines, and acyl-protected uridines with the use of a fluorous analogue of the Lawesson's reagent leads to thioamides, thiophenes, 1,3-thiazoles, 1,3,4-thiadiazoles, and acyl-protected 4-thiouridines. The isolation of the final products in high yields is achieved in most cases by a simple filtration (fluorous solid-phase extraction).

Reaction of alk-3-yn-1-ones with o-phenylenediamines provides an effective method with high atom economy for the synthesis of diversely substituted benzodiazepines and conjugated enaminones. This microwave-accelerated reaction proceeds in ethanol in the absence of a catalyst and leads to benzyl-substituted 1,5-benzodiazepines with good yields (70-92%). A room temperature protocol with the same set of reagents (stabilized with triethylamine) leads to enaminones (3-amino-2-alkenones, 70-99%). The tautomer formed and the regio- and stereochemistry of the process are confirmed by the X-ray crystallographic structure determination of 2-(4-methylbenzyl)-4-phenyl-3H-benzo[b][1,5]diazepine and (Z)-3-[(2-amino-4,5-dimethylphenyl) amino]-4( 4-tert-butylphenyl)-1-(4-chlorophenyl) but-2-en-1-one.

Conjugated polyalkynyl carbon chains, candidates for molecular wires, ( η 5 -C 5 Me 5 )Re(NO)(PPh 3 )(CC) n (Ph 3 P)(ON)Re( η 5 -C 5 Me 5 ) ( n =2 (Re*C 4 Re*), 4 (Re*C 8 Re*), 6 (Re*C 12 Re*)), have been deposited as thin films on air passivated copper surfaces and examined by X-ray photoelectron spectroscopy before and after exposure to air for various periods of time. The reactivity patterns of these thin films have been determined by examination of the oxidation state of Re and the chemical states of carbon, oxygen and phosphorus. Rhenium, which is zero valent in the starting compounds (Re*C 4 Re*), (Re*C 8 Re*) and (Re*C 12 Re*) reacts to form Re 3+ , Re 4+ and Re 5+ . Their thin film reactivities will be discussed and compared to their solution electrochemistry. We have found Re*C 4 Re* and Re*C 8 Re* to be more reactive than Re*C 12 Re* in agreement with the cyclic voltammetry results.

Reaction of the butadiynyl complex (η5-C5Me5)Re(NO)(PPh3)(C⋮CC⋮CH) (ReC4H) with Cu(OAc)2 (pyridine, 80 °C) gives the μ-octatetraynediyl complex ReC8Re (70%). Analogous cross-coupling of ReC4H and ReC2H gives (after chromatography) ReC4Re (14%), ReC6Re (44%), and ReC8Re (15%). Longer sp carbon chains are accessed by reactions of ReC4H with n-BuLi and CuI, which give ReC4Cu. This isolable species is treated in situ with BrC⋮CSiEt3 or BrC⋮CC⋮CSiMe3 (excess EtNH2, THF) to give ReC6SiEt3 or ReC8SiMe3 (84−77%). Desilylations (wet n-Bu4N+F-) yield ReC6H or ReC8H (88−73%). Then Cu(OAc)2 (pyridine, 50 °C) gives ReC12Re or ReC16Re (71−67%). The former is also available from ReC4Cu and BrC⋮CC⋮CBr (45%), and ReC10Re can be accessed by cross-coupling. ReC6H and ReC8H are similarly converted to ReC10SiR3 (R = Me, Et; 51−26%) and ReC12SiMe3 (43%). Desilylation of ReC10SiR3 gives labile ReC10H, but only black powder is obtained from ReC12SiMe3. In situ coupling of ReC10H gives ReC20Re (52−34%), which unlike lower homolog...

The structural investigation of the phosphoroorganic selenium-containing title compound C10H20O6P2Se (1) was carried out. The structure of 1 has been determined by X-ray analysis and correlated with the solid state NMR studies, its purity and identity was confirmed by elemental analysis. The following crystal data were found: triclinic, P1, a = 5.6557(6) A, b = 10.2717(8) A, c = 13.761(1) A, α = 105.580(7)β, p = 90.992(7)°, γ = 101.745(8)°, and Z = 2. Two six-membered rings in the molecule of 1 are in the chair conformation. The selenium atom which bridges the rings is situated axially with respect to both rings. The exocyclic oxygens are, consequently, in equatorial positions.

Synthesis of highly substituted 3-fluorofurans is reported. The sequence began with preparation of tert-butyldimethylsilyl alk-1-en-3-yn-1-yl ethers from 1,4-disubstituted alk-3-yn-1-ones. Subsequent fluorination of alkenynyl silyl ethers with Selectfluor gave 2-fluoroalk-3-yn-1-ones in almost quantitative yield. Subsequent 5-endo-dig cyclizations using chlorotriphenylphosphine gold(I)/silver trifluoromethanesulfonate (5/5 mol%), N-bromo- or N-iodosuccinimide and gold(I) chloride/zinc bromide (5/20 mol%), all at room temperature, provided a facile method for the generation of substituted 3-fluoro-, 3-bromo-4-fluoro-, and 3-fluoro-4-iodofurans in good yields. Also, 2,2-difluoroalk-3-yn-1-ones were prepared by fluorination of alk-3-yn-1-ones under organocatalytic conditions. The structures of (Z)-tert-butyldimethylsilyl but-1-en-3-yn-1-yl ether, 3-bromo-4-fluorofuran, and 3-fluoro-4-(phenylethynyl)furan were confirmed by X-ray crystallography.

Synthesis of highly substituted 3-fluorofurans is reported. The sequence began with preparation of tert-butyldimethylsilyl alk-1-en-3-yn-1-yl ethers from 1,4-disubstituted alk-3-yn-1-ones. Subsequent fluorination of alkenynyl silyl ethers with Selectfluor gave 2-fluoroalk-3-yn-1-ones in almost quantitative yield. Subsequent 5-endo-dig cyclizations using chlorotriphenylphosphine gold(I)/silver trifluoromethanesulfonate (5/5 mol%), N-bromo- or N-iodosuccinimide and gold(I) chloride/zinc bromide (5/20 mol%), all at room temperature, provided a facile method for the generation of substituted 3-fluoro-, 3-bromo-4-fluoro-, and 3-fluoro-4-iodofurans in good yields. Also, 2,2-difluoroalk-3-yn-1-ones were prepared by fluorination of alk-3-yn-1-ones under organocatalytic conditions. The structures of (Z)-tert-butyldimethylsilyl but-1-en-3-yn-1-yl ether, 3-bromo-4-fluorofuran, and 3-fluoro-4-(phenylethynyl)furan were confirmed by X-ray crystallography.

The reaction of readily available dialkyltrimethylsilyl phosphites (RO)2POSiMe3 5 with sulfur dichloride leads to tetra-alkyl sym-monothio-pyrophosphates (RO)2P(O)SP(O)(OR)2 1 in high yield. The method is suitable for the synthesis of tetra t-butyl thiopyrophosphate 1d.

[formula: see text] The reaction of secondary and primary alcohols with highly fluorinated 3,4,5-tris(5,5,6,6,7,7,8,8,9,9,10,10,11,11,12,12,12-heptadecafluorododecan- 1-yloxy)benzoic acid in the presence of Ph3P and DIAD in THF at room temperature (fluorous Mitsunobu) resulted in a simple, chromatography-free isolation protocol with excellent yields (83-96%).

3,4',5,7-tetraacetyl quercetin (1) was isolated from the heartwood of Adina cordifolia. The structure was elucidated on the basis of spectral evidence.

Fluorination of substrates (I) with Selectfluor gives 2-mono-fluorobutynones (II) which undergo subsequent 5-endo-dig cyclization in the presence of a gold(I)-catalyst and silver triflate providing 2,5-diaryl-substituted 3-fluorofurans in high yields.

Reactions of 5-p-tolylethynyl-2′-deoxyuridine and 3′,5′-di-O-acetyl-5-p-tolylethynyl-2′-deoxyuridine with Co2(CO)8 in THF gave 5-p-tolC2[Co2(CO)6]-2′-deoxyuridine and 3′,5′-di-O-acetyl-5-p-tolC2[Co2(CO)6]-2′-deoxyuridine (92 and 66%).

[1317-39-1] Cu2O (MW 143.08) InChI = 1S/2Cu.O InChIKey = BERDEBHAJNAUOM-UHFFFAOYSA-N (weak base; activates halides towards nucleophilic substitution;1 forms carbenoid intermediates from diazo compounds2 and radicals from arenediazonium salts;3 activates isocyanides towards 1,1-addition4) Physical Data: mp 1235 °C; d ∼6 g cm−3. Solubility: insol most organic solvents; slightly sol quinoline and benzonitrile;1a variously sol acids (salt formation, in some cases disproportionation to Cu0 and CuII). Form Supplied in: red to brown powder; widely available. Typical impurities: Cu, CuO,5 NaCl,5 stabilizers (e.g. gelatine,5 oil, zinc stearate), moisture.5 For reactions in anhydrous media the reagent is vacuum-dried before use. Preparative Methods: since reactions involving Cu2O are heterogeneous, they may critically depend on the particle size.6b An active preparation is obtained by reduction of CuII solutions7 but may suffer deactivation at high reaction temperatures1a octahedral,54 cubic,55, 56 thread/wire,56 tube/rod,57 crystalline,58 amorphous,59 or poly(vinyl alcohol) coated60 nanoparticles can be prepared. Handling, Storage, and Precautions: Cu2O is incompatible with alkynes, diazonium salts, and diazo compounds. Copper compounds are moderately toxic.

Reactions of (η5-C5Me5)Re(NO)(PPh3)(C⋮CC⋮CR) (R = Me, H) and (t-BuO)3W⋮W(O-t-Bu)3 give (t-BuO)3W⋮CR and the title complex (79−76%), which crystallizes from toluene as a solvated tert-butoxy-bridged dimer. The NMR, IR, and crystallographic properties establish dominant Re−C⋮C−C⋮W as opposed to +ReCCCW- character.

5-(4-Bromophenyl)-3-iodo-2-(4-methylphenyl)furan 2-(4-Bromophenyl)oxirane 4-Ethynyltoluene Lithium diisopropylamide 1-(4-Bromophenyl)-4-methylphenyl)but-3-yn-1-ol Chromium trioxide 1-(4-Bromophenyl)-4-methylphenyl)but-3-yn-1-one N-Isosuccinamide Keywords: electrophilic cyclization; iodosuccinamide; halofurans; unsymmetrical iodofurans; hydriotic acid; sonogashira coupling-addition-cyclocondensation; one-pot; safety; waste disposal

Starting with 5-iodo-2'-deoxyuridine, a series of 5-alkynyl-2'-deoxyuridines (with n-propyl, cyclopropyl, 1-hydroxycyclohexyl, p-tolyl, p-tert-butylphenyl, p-pentylphenyl, and trimethylsilyl alkyne substituents) have been synthesized via the palladium-catalyzed (Sonogashira) coupling reaction followed by a simplified isolation protocol (76-94% yield). The cytotoxic activity of modified nucleosides against MCF-7 and MDA-MB-231 human breast cancer cells has been determined in vitro. 5-Ethynyl-2'-deoxyuridine, the only nucleoside in the series containing a terminal acetylene, is the most potent inhibitor with IC(50) (microM) 0.4+/-0.3 for MCF-7 and 4.4+/-0.4 for MDA-MB-231.

5-Endo-dig cycloisomerization of 1,4-di- and 1,2,4-trisubstituted but-3-yn-1-ones in the presence of a catalytic amount of zinc chloride (10 mol %) in dichloromethane at room temperature (22 °C) provides 2,5-di- and 2,3,5-trisubstituted furans in high yields (85−97%).

[reaction: see text] Thionation of amides, 1,4-diketones, N-(2-oxoalkyl)amides, N,N'-acylhydrazines, and acyl-protected uridines with the use of a fluorous analogue of the Lawesson's reagent leads to thioamides, thiophenes, 1,3-thiazoles, 1,3,4-thiadiazoles, and acyl-protected 4-thiouridines. The isolation of the final products in high yields is achieved in most cases by a simple filtration (fluorous solid-phase extraction).

[reaction: see text] 5-Endo-dig electrophilic cyclization of 1,4-diaryl but-3-yn-1-ones with N-bromosuccinimide or N-iodosuccinimide/acetone and iodine monochloride/CH(2)Cl(2), at room temperature, in the absence of base, provides 3-halo-2,5-diarylfurans with excellent regiocontrol and high yields (81-94%).

The conformation of a representative molecule of a new, potent class of antiviral-active modified nucleosides is determined. A bicyclic nucleoside, 3-(2'-deoxy-beta-D-ribofuranosyl)-6-(4-methylphenyl)-2,3-dihydrofuro[2,3-d]pyrimidin-2-one, shows C2'-endo and C3'-endo ribose conformations in solution (63:37, 37 degrees C; DMSO-d6), as determined by 1H NMR studies. The crystal structure of a 3',5'-di-O-acetyl-protected derivative (monoclinic, P21, a/b/c= 6.666(1)/12.225(1)/24.676(2) A, beta=90.24(1) degrees , Z=4) shows exclusively C2'-endo deoxyribose puckering. The base is found in the anti position both in solution and in crystalline form.

5-Endo-dig electrophilic cyclization of 5-alkynyl-2'-deoxyuridines with N-iodosuccinimide or N-bromosuccinimide in acetone at room temperature gives 3-(2'-deoxy-beta-D-ribofuranosyl)-5-halo-2,3-dihydrofuro[2,3-d]pyrimidin-2-ones that usually precipitate from the reaction mixture (86-74%).

Reactions of 5-p-tolylethynyl-2′-deoxyuridine and 3′,5′-di-O-acetyl-5-p-tolylethynyl-2′-deoxyuridine with Co2(CO)8 in THF gave 5-p-tolC2[Co2(CO)6]-2′-deoxyuridine and 3′,5′-di-O-acetyl-5-p-tolC2[Co2(CO)6]-2′-deoxyuridine (92 and 66%).

Fluorous technology, a modern approach that exploits phase separation, is reviewed. Strategies towards organic synthesis are outlined and application examples given.

Benzyloxycarbonyl N-protected and C-terminus methyl ester protected amino acids react in THF in the presence of 4-methylmorpholine and fluorous condensation reagent, 2-chloro-4,6-bis](heptadecafluorononyl)oxy]-1,3,5-triazine, to form di- and tripeptides that are isolated without the use of fluorous solvent in very good yields (98-91%).

Efficient, general synthesis of oxophosphoranesulphenyl chlorides ABP(O)SCl 2 based on the reaction of phosphorus trimethylsilylthionoesters ABP(S)OSiMe3 7 with chlorinating agents is described.

A novel highly efficient synthesis of sym-tetra-alkyl monothio- and monoseleno-pyrophosphates (RO)2P(O)XP(O)(OR′)2(X = S,Se) based on the condensation of dialkoxyoxophosphorane-sulphenyl or -selenenyl chlorides (RO)2P(O)XCl (X = S,Se) with dialkyl trimethylsilyl phosphites (RO)2POSiMe3(9) is described. Remarkably selective reaction of a O,O′-dialkyl O″-trimethylsilyl selenophosphate (RO)2P(Se)OSiMe3(13) with sulphuryl dichloride in the presence of an equimolar amount of a phosphite (9) leads to the formation of sym-monoselenopyrophosphates in excellent yield. A new rearrangement in phosphorus chemistry, sym-monoselenopyraphosphates (11) to asym-monoselenopyrophosphates (12), has been observed.