Iodo Groups Research Articles

Synthesis of novel cyclic oligosaccharides: beta-1,6-thio-linked cycloglucopyranosides.

[structure: see text] A protocol for the synthesis of novel cyclic beta-1,6-S-linked glucopyranosides is developed. The key intermediate is a linear thiooligosaccharide bearing an iodo group at C-6 of the nonreducing sugar and a thioacetyl group at the anomeric center of the reducing end sugar. The crucial macrocyclization step was achieved through base-promoted intramolecular S(N)2 glycosylation in remarkably high yields (92-95%) and with well-controlled stereochemistry.

Trimethylgermyl group in Pauson–Khand reaction

The Pauson–Khand reaction of enynes possessing the trimethylgermyl group at the alkyne terminus stereoselectively afforded the corresponding bicyclo[3.3.0]octenone and bicyclo[4.3.0]decenone skeletons. The formed trimethylgermyl group of the bicyclic compound was then converted to the iodo group, which was used for further elaboration. Thus the trimethylgermyl group at the triple bond terminus was shown to become a precursor for other appendages.

Nickel-Catalyzed Asymmetric Grignard Cross-Coupling of Dinaphthothiophene Giving Axially Chiral 1,1‘-Binaphthyls

Asymmetric cross-coupling of dinaphtho[2,1-b:1',2'-d]thiophene with ArMgBr (Ar = Ph, 4-MeC6H4, 4-MeOC6H4) proceeded with high enantioselectivity in THF at 20 degrees C in the presence of 3 mol % of a nickel catalyst generated from Ni(cod)2 and a chiral oxazoline-phosphine ligand to give high yields of axially chiral 2-mercapto-2'-aryl-1,1'-binaphthyls, whose enantiomeric excesses are over 93%. The mercapto group in the chiral binaphthyl was converted into iodo, boryl, and phosphino groups without racemization.

Synthesis and electronic properties of regioisomerically pure oxochlorins.

We describe a two-step conversion of C-alkylated zinc chlorins to zinc oxochlorins wherein the keto group is located in the reduced ring (17-position) of the macrocycle. The transformation proceeds by hydroxylation upon exposure to alumina followed by dehydrogenation with DDQ. The reactions are compatible with ethyne, iodo, ester, trimethylsilyl, and pentafluorophenyl groups. A route to a spirohexyl-substituted chlorin/oxochlorin has also been developed. Representative chlorins and oxochlorins were characterized by static and time-resolved absorption spectroscopy and fluorescence spectroscopy, resonance Raman spectroscopy, and electrochemistry. The fluorescence quantum yields of the zinc oxochlorins (Phi(f) = 0.030-0.047) or free base (Fb) oxochlorins (Phi(f) = 0.13-0.16) are comparable to those of zinc tetraphenylporphyrin (ZnTPP) or free base tetraphenylporphyrin (FbTPP), respectively. The excited-state lifetimes of the zinc oxochlorins (tau = 0.5-0.7 ns) are on average 4-fold lower than that of ZnTPP, and the lifetimes of the Fb oxochlorins (tau = 7.4-8.9 ns) are approximately 40% shorter than that of FbTPP. Time-resolved absorption spectroscopy of a zinc oxochlorin indicates the yield of intersystem crossing is >70%. Resonance Raman spectroscopy of copper oxochlorins show strong resonance enhancement of the keto group upon Soret excitation but not with Q(y)()-band excitation, which is attributed to the location of the keto group in the reduced ring (rather than in the isocyclic ring as occurs in chlorophylls). The one-electron oxidation potential of the zinc oxochlorins is shifted to more positive potentials by approximately 240 mV compared with that of the zinc chlorin. Collectively, the fluorescence yields, excited-state lifetimes, oxidation potentials, and various spectral characteristics of the chlorin and oxochlorin building blocks provide the foundation for studies of photochemical processes in larger architectures based on these chromophores.

Synthesis, nicotinic acetylcholine receptor binding, and antinociceptive properties of 2-exo-2-(2',3'-disubstituted 5'-pyridinyl)-7-azabicyclo[2.2.1]heptanes: epibatidine analogues.

A number of 2',3'-disubstituted epibatidine analogues were synthesized and evaluated in vitro for potency at nicotinic acetylcholine receptors (nAChRs) and in vivo for antinociception activity in the tail-flick and hot-plate models of acute pain and for their ability to affect core body temperature. Compounds that possessed electron-withdrawing groups (F, Cl, Br, and I) in both the 2'- and the 3'-positions showed affinities at the nAChR similar to epibatidine. However, in vivo efficacy did not correlate with affinity. 2-exo-(3'-Amino-2'-chloro-5'-pyridinyl)-7-azabicyclo[2.2.1]heptane (2i), an epibatidine analogue possessing an electron-releasing amino group in the 3'-position, produced the highest affinity. Compound 2i was also the most selective epibatidine analogue with a K(i) of 0.001 nM at alphabeta nAChRs, which is 26 times greater than that of epibatidine, and a alphabeta/alpha(7) K(i) ratio of 14,000, twice that of epibatidine. In vivo testing revealed that this compound potently inhibited nicotine-induced antinociception with AD(50) values below 1 microg/kg. Surprisingly, this same compound was also an agonist at higher doses (ED(50) approximately 20 microg/kg). Thus, the addition of the 3'-amino group to epibatidine confers potent antagonist activity to the compound with little effect on agonist activity. 2,3-Disubstituted epibatidine analogues possessing a 2'-amino group combined with a 3'-bromo or 3'-iodo group showed in vitro and in vivo nAChR properties similar to nicotine.

3,3-Dimethyl-1-butyne complexes of tungsten(II). Crystal structures of [WI 2(CO)(NCPh)(η 2-HC 2Bu t) 2] and [WI 2(CO){P(OR) 3} 2(η 2-HC 2Bu t)] (R=Me and Et)

Reaction of [WI 2(CO) 3(NCMe) 2] with two equivalents of 3,3-dimethyl-1-butyne (HC 2Bu t ) in CH 2Cl 2 at room temperature, in the absence of light, afforded the bis(alkyne) complex, [WI 2(CO)(NCMe)(η 2-HC 2Bu t ) 2], 1, in high yield. Nitrile exchange reactions of 1 with NCR (R=Et, Pr i , Bu t , Ph) gave the complexes [WI 2(CO)(NCR)(η 2-HC 2Bu t ) 2], ( 2– 5). Complex 5 (R=Ph) was structurally characterised by a single crystal X-ray diffraction study and has a pseudo-octahedral geometry, with cis and parallel 3,3-dimethyl-1-butyne ligands, trans to the two mutually cis-iodo ligands, in the equatorial plane. The benzonitrile and carbon monoxide ligands are in the axial sites. The tert-butyl groups on the alkyne ligands are trans to one another. Treatment of 1 with two equivalents of P(OR) 3 in Et 2O afforded the bis(phosphite) complexes, [WI 2(CO){P(OR) 3} 2(η 2-HC 2Bu t )] {R=Me, 6; Et 7; Pr i 8}. The structures of 6 and 7 have been crystallographically determined with both complexes having similar pseudo-octahedral structures. The structures may be represented by two cis phosphite ligands in the equatorial plane with an iodo group and the carbonyl ligand, whilst the second iodo-group and the 3,3-dimethyl-1-butyne ligand are in the axial positions. Reaction of 6– 8 with one equivalent of Ag[BF 4] in acetonitrile, in the absence of light, yielded the cationic complexes, [WI(CO)(NCMe){P(OR) 3} 2(η 2-HC 2Bu t )][BF 4] ( 9– 11). Detailed 1H, 13C{ 1H}, 13C 1H and 31P{ 1H}-NMR studies are described, which gave comprehensive structural information on these complexes in solution.

Improvement in the properties of 3-phenyl-3-trifluoromethyldiazirine based photoreactive bis-glucose probes for GLUT4 following substitution on the phenyl ring.

We have developed two novel 3-phenyl-3-trifluoromethyldiazirinyl bis-glucose derivatives to investigate the properties of the adipocyte glucose transporter GLUT4. These compounds were substituted by electron-withdrawing (iodo and nitro) groups on the aromatic ring of 3-phenyl-3-trifluoromethyldiazirine photophore and were found to be more photosensitive than compounds without such substituents. The compounds were used as inhibitors of insulin-stimulated glucose transport activity in order to assess half-maximal inhibition or relative affinity values for GLUT4. The affinities were found to be 60-130 times higher than the parent compound D-glucose. Because of the increased photo-reactivity and high affinity these compounds will be useful in studies directed at further elucidation of GLUT4 function.

Polymer-Supported Hypervalent Iodine Reagents

Polymer-supported hypervalent iodine reagents, bearing (diacetoxy)iodo, (dihalo)iodo, (hydroxy)(tosyloxy)iodo, (hydroxy)(phosphoryloxy)iodo, aryliodonium, 1,2-benziodoxol-3-one, and hypervalent iodine groups as counter anions, can be used for various oxidative functional group conversions of substrates. These polymer species can be recovered quantitatively by simple filtration, and can be regenerated and reused. Thus, these polymer-supported hypervalent iodine reagents are very useful, effective, and environmentally benign reagents for organic synthesis.

Synthesis and Biological Activity of a Photoaffinity Etoposide Probe

The epipodophyllotoxin etoposide is a potent and widely used anticancer drug that targets DNA topoisomerase II. The synthesis, photochemical, and biological testing of a photoactivatable aromatic azido analogue of etoposide also containing an iodo group is described. This azido analogue should prove useful for identifying the etoposide interaction site on topoisomerase II. Irradiation of the azido analogue and an aldehyde-containing azido precursor with UV light produced changes in their UV–visible spectra that were consistent with photoactivation. The azido analogue strongly inhibited topoisomerase II and inhibited the growth of Chinese Hamster Ovary cells. Azido analogue-induced topoisomerase II–DNA covalent complexes were significantly increased subsequent to UV irradiation of drug-treated human leukemia K562 cells as compared to etoposide-treated cells. These results suggest that the photoactivated form of etoposide is a more effective topoisomerase II poison either by interacting directly with the enzyme or with DNA subsequent to topoisomerase II-mediated strand cleavage.

Palladium-copper catalyzed synthesis of benzofused heterocycles with two heteroatoms: novel and highly regio- and stereoselective syntheses of (E)-2-(2-arylvinyl)-3-tosyl-2,3-dihydro-1,3-benzothiazoles and (E)-2-alkyl(aryl)idene-3,4-dihydro-2H-1,4-benzothiazines.

A highly novel, general, and convenient palladium and copper-catalyzed procedure has been developed for the synthesis of (E)-2-(2-arylvinyl)-3-tosyl-2,3-dihydro-1,3-benzothiazoles 28-40. 3-(2-Aminophenylthio)prop-1-yne 1 reacts with aryl iodides 2-14 under palladium-copper catalysis to yield the disubstituted alkynes 15-27 which after tosylation undergo a novel cyclization with CuI in the presence of triethylamine in THF to (E)-2-(2-arylvinyl)-3-tosyl-2,3-dihydro-1,3-benzothiazoles 28-40 rather than to the expected 3-alkylidene-4-tosyl-3,4-dihydro-2H-1,4-benzothiazines 41. The reaction is highly regio- and stereoselective. The synthesis of 2-(2-arylethyl)-3-tosylbenzothiazolines 42-47, 2-(2-arylvinyl)benzothiazoles 48-54, and a novel 5-substituted uracil derivative 55 of potential biological importance is also being reported. Similarly, the palladium-copper-catalyzed arylation of S-[2-(N-prop-2'-ynyl)aminophenyl]-N,N-dimethylthiocarbamate 58 with aryl iodides yields the disubstituted alkynes 59 which on cyclization with KOH in methanol leads to (E)-2-(2-aryl)methylidene-3,4-dihydro-2H-1,4-benzothiazines 61. The reaction of the diiodo compounds 12-14a, however, with 58 under palladium-copper-catalyzed reactions involves the participation of only one of the iodo groups in the heteroannulation process giving compounds 61i and 61j. These are amenable to further palladium-catalyzed reactions and afford polyunsaturated heteroaromatic compounds 62 and 63.

Highly regioselective iodoperfluoroalkylation of allenes with perfluoroalkyl iodides upon irradiation with near-UV light

Upon irradiation through Pyrex with a xenon lamp ( hν>300 nm), perfluoroalkyl iodides add to terminal allenes regioselectively to afford the corresponding iodoperfluoroalkylated products, where perfluoroalkyl and iodo groups are selectively introduced into the terminal and central carbons of allenes, respectively.

Synthesis and characterization of thiophene-containing liquid crystals

Six series of liquid crystal materials containing a 2,5-disubstituted thiophene unit were synthesized. The liquid crystal compounds obtained were characterized by NMR, differential scanning calorimetry, polarizing optical microscopy and X-ray diffraction techniques. The properties of liquid crystalline phases were investigated as a function of spacer units, number of aromatic core rings and different terminal moieties. Cyano, methoxy and iodo groups were used as terminal groups. It is found that: (i) compounds having one thiophene ring and one phenyl ring connected by an ester group, with a length/breadth value of 2.1, exhibit no mesophase, while other compounds containing two biphenyl rings, with a length/breadth ratio of 2.7, show mesophases; (ii) the polarity of terminal groups and the flexible spacer length significantly affect the thermal behaviour of these compounds; (iii) the nematic transition range of cyano-containing compounds decreases with increasing length of the flexible spacer, and long alkenyloxy chains tend to facilitate the formation of the smectic phase and suppress the nematic phase in all the mesogenic compounds synthesized.

Unprecedented Cesium and Potassium Fluorides Catalyzed Trialkylsilylation and Tributylstannylation of Terminal Alkynes with Trifluoromethyl-Trialkylsilanes and -Tributylstannane

Cesium and potassium fluorides promoted trialkylsilylation and tributylstannylation of terminal alkynes with trifluoromethyl-trialkylsilanes and -tributylstannane were found to give 1-silyl- and 1-tributylatannyl-alkynes in high yield. The present reactions are applicable to 1-alkynes having a wide range of functional groups such as acetal, iodo, silyl, amino, amido and carbonyl (except for aldehyde) groups.

Syntheses of new unsymmetrically dodecakis(trifluoroethoxy)-substituted metallophthalocyanines by a palladium-catalyzed cross-coupling reaction

Novel unsymmetrical vanadyl and zinc dodecakis(2,2,2-trifluoroethoxy)phthalocyaninates with an iodo group were synthesized by a statistical condensation route. The palladium-catalyzed coupling reaction between such monoiodinated metallophthalocyanines and terminal acetylenic derivatives gave various new unsymmetrically dodecakis(2,2,2-trifluoroethoxy)-substituted metallophthalocyanines with extended exocyclic π-conjugation. Unsymmetrical zinc dodecakis(2,2,2-trifluoroethoxy)phthalocyaninate with a nitro group was also prepared for comparison. All the target phthalocyanines were separated by common col umn chromatography and characterized by elemental analysis, ir and 1H-nmr, uv-visible and fast-atombombardment mass spectroscopy.

2,2′:6′,2″-Terpyridine complexes of molybdenum(II) and tungsten(II). X-ray crystal structures of [MoI(CO)(terpy)(η 2-PhC 2Ph)]I and [WI(terpy)(η 2-PhC 2Ph) 2]I·CDCl 3

Equimolar quantities of [MI 2(CO) 3(NCMe) 2] (M=Mo or W) and terpy (terpy=2,2′:6′,2″-terpyridine) react in CH 2Cl 2 at room temperature to give the cationic complexes [MI(CO) 3(terpy)]I ( 1 and 2) in high yield. Treatment of [MoCl(GeCl 3)(CO) 3(NCMe)(PPh 3)] with one equivalent of terpy affords [Mo(GeCl 3)(CO) 2(PPh 3)(terpy)]Cl ( 3) in good yield. Reaction of [MI 2(CO)(NCMe)(η 2-RC 2R) 2](M=Mo, W; R=Ph; for M=W only, R=Me) with an equimolar quantity of terpy in CH 2Cl 2 at room temperature gives the cationic complexes [MI(CO)(terpy)(η 2-RC 2R)]I ( 4 and 5) or the crystallographically characterised cationic complex [WI(terpy)(η 2-PhC 2Ph) 2]I ( 6). Equimolar quantities of [WI(CO)(terpy)(η 2-MeC 2Me)]I( 5) and Na[BPh 4] react to give the anion-exchanged product, [WI(CO)(terpy)(η 2-MeC 2Me)][BPh 4] ( 7). The X-ray crystal structure of [MoI(CO)(terpy)(η 2-PhC 2Ph)]I shows the three nitrogen atoms of the terpy bonded in the equatorial plane of an octahedron together with the carbonyl group. The iodo and diphenylacetylene ligands are mutually trans- to each other in the axial positions. The structure of [WI(terpy)(η 2-PhC 2Ph) 2]I·CDCl 3 ( 6) has a distorted octahedral geometry, with the three nitrogen atoms of the terpy ligand in a mer-configuration, with two cis-and parallel diphenylacetylene ligands and an iodo group occupying the other three mer-sites.

1,1'-Diiodo-3,3'-bis(trimethylsilyl)ferrocene

In the structure of the title compound, [Fe(C 8 H 12 ISi) 2 ], the cyclopentadienyl rings are fully eclipsed. The trimethylsilyl groups are staggered by 141.0(4)° and the iodo groups by 69.6 (3)°.

Molecular structure and iodine oxidative-thermal decarbonylation of the seven-coordinate complex [MoI2(CO)3(NCMe)2] to give the crystallographically characterised complex mer-[MoI3(NCMe)3

The X-ray crystal structure of the seven-coordinate complex [MoI2(CO)3(NCMe)2] (1) has been determined and shows discrete molecules. The geometry of the metal coordination sphere conforms to a distorted capped octahedron with a carbonyl group in the unique capping position. The capped face contains two carbonyl ligands and an iodo group, the uncapped face two MeCN ligands and an iodo group. The low temperature 13C n.m.r. spectrum (−70 °C, CD2Cl2) shows a single band at δ = 222.8 ppm, which suggests that the complex is rearranging more rapidly than the n.m.r. timescale at this temperature. Refluxing a 2:1 mixture of [MoI2 (CO)3(NCMe)2] and I2 in MeCN for 2h gives the crystallographically characterised molybdenum(III) complex mer-[MoI3(NCMe)3] (2) in quantitative yield.

Chemistry of cage-shaped hydrocarbons. Ring transformations on a tricyclo[5.2.1.0 4,10]decane system

A series of triquinane (tricyclo[5.2.1.04,10]decane) derivatives were prepared from oxidation of pentaquinandiene 1. Ozonolysis of 1, followed by reduction, yielded three products 4, 5, and 6 with poly-hydroxy groups. The hydroxy group of 5 was transformed to an iodo group in 8 with triphenylphosphine and iodine. An attempted dehydroiodination of 8 with base upon heating produced 10 with an unexpected geometry. The structure of an isomer 11 has been solved by single-crystal X-ray diffraction analysis, in which an exo-oriented cyclopropyl group indicated that an inversion has happened at C(3). The mechanism of the reaction from 8 to 10 was depicted as going through a multi-step sequence as outlined in Scheme 3.

Syntheses of (Trifluoromethyl)imidazoles with Additional Electronegative Substituents. An Approach to Receptor-Activated Affinity Labels

Electrophilic substitution in 2- and 4-(trifluoromethyl)imidazoles provides derivatives containing one or two nitro, chloro, bromo, or iodo groups. Fluoro and chloro derivatives were also prepared by photochemical trifluoromethylation of the respective haloimidazole. The results demonstrate that (trifluoromethyl)imidazoles behave fairly typically under the conditions of electrophilic nitration and halogenation. Of the alternative routes to the desired bifunctional and trifunctional imidazoles, electrophilic substitution on the preformed (trifluoromethyl)imidazole appears to be the method of choice in most cases. A large number of the products show herbicidal or insecticidal activity.

The synthesis, molecular structure and fluxional properties of the 1-phenylpropyne complex [WI 2(CO){Ph 2P(CH 2)PPh 2}( η2-MeC 2Ph)

Reaction of [WI 2(CO){Ph 2P(CH 2)PPh 2}( η 2-MeC 2Ph)] mono(1-phenylpropyne) complex [WI 2(CO){Ph 2P(CH 2)PPh 2}( η 2-MeC 2Ph)] ( 1) in high yield. The structureof 1 has been determined by single crystal X-ray diffraction. The structure can best be described as a distorted octahedron with the two phosphorus atoms of the Ph 2P(CH 2)PPh 2 ligand trans to an iodo- and a 1-phenylpropyne ligand in the equatorial plane and the other iodo and carbonyl groups in the axial sites. The two bond lengths of the two W-I and those of the two W-P bonds are quite different reflecting the nature of the trans-ligands. Variable temperature 31P NMR studies have been carried out on 1, which has enabled the activation energy for alkyne rotation, to be calculated.