Synthesis of O-(2-[~(18)F]fluoroethyl)-L-tyrosine and its biological evaluation in B16 melanoma-bearing mice as PET tracer for tumor imaging

O-(2-[18F]fluoroethyl) -L-tyrosine([18F]FET) ,a fluorine-18 labeled analogue of tyrosine,has been syn-thesized and biologically evaluated in tumor-bearing mice. The whole synthesis procedure is com-pleted within 50 min. The radiochemical yield is about 40%(no decay corrected) and radiochemical purity more than 97% after simplified solid phase extraction. [18F]FET shows rapid,high uptake and long retention in the tumor as well as low uptake in the brain. The ratios of tumor-to-muscle(T/M) and tumor-to-blood(T/B) of [18F]FET are similar to those of [18F]FDG,but the ratios of tumor-to-brain(T/Br) are 2-3 times higher than that of [18F]FDG. Autoradiography of [18F]FET demonstrates a remarkable accumulation in melanoma with high contrast. It appears to be a probable competitive candidate for melanoma imaging with PET.     

<Emphasis Type="Italic">O</Emphasis>- and <Emphasis Type="Italic">N</Emphasis>-Alkylation of <Emphasis Type="Italic">N</Emphasis>-halosuccinimides in ionic reactions with 1-phenyltricyclo [4.1.0.0<Superscript>2,7</Superscript>]heptane

N-Bromo and N-chlorosuccinimides add to 1-phenyltricyclo[4.1.0.0^2,7]heptane in CH₂Cl₂ with cleavage of the C(1)-C(7) bond to give isomeric 1 : 1 Markownikoff-type endo, anti-adducts of the norpinane structure in a ∼3 :7 ratio corresponding to N and O alkylation of succinimide.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No.2, pp. 457–460, February, 2005     

Preparation of two triflate precursors for <Emphasis Type="Italic">O</Emphasis>-(2-[<Superscript>18</Superscript>F] fluoroethyl)-<Emphasis Type="Italic">L</Emphasis>-tyrosine used in positron emission tomography (PET)

Two novel triflate precursors for radiolabelling of L-tyrosine in positron emission tomography (PET) for tumor imaging, O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine methyl ester 9a and O-(2-trifluoromethanesulfonyloxyethyl)-N-(tert-butoxycarbonyl)-L-tyrosine tert-butyl ester 9b, are synthesized. The triflate agent, 9a or 9b, is prepared by esterification of methanol or transesterification of tert-butyl acetate with L-tyrosine, protection of the amine group with di-tert-butyl dicarbonate, alkylation with chlorohydrin, and triflation with trifluoromethanesulfonic anhydride in four steps with overall yields of 30% and 15%, respectively.     

Synthesis and reductive reactions of 2,3-dioxo-2,3-dihydrobenzo[<Emphasis Type="Italic">b</Emphasis>]furo[2,3-<Emphasis Type="Italic">f</Emphasis>]-, -[2,3-<Emphasis Type="Italic">g</Emphasis>]-, and -[3,2-<Emphasis Type="Italic">e</Emphasis>]indoles

The Sandmeyer reaction was used to prepare 2,3-dioxo-2,3-dihydrobenzo[b]furoindoles which could be reduced with diborane or with complex hydrides to give the corresponding unsubstituted as well as the 3-hydroxybenzo[b]furoindoles.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No 11, pp. 1683–1689, November, 2004.     

Ionic Liquid Promoted One-Pot Synthesis of Furo[2,3-<Emphasis Type="Italic">d</Emphasis>]pyrimidine-2,4(1<Emphasis Type="Italic">H</Emphasis>,3<Emphasis Type="Italic">H</Emphasis>)-diones

Summary. The three-component condensation of aldehyde, N,N′-dimethylbarbituric acid and alkyl or aryl isocyanide afforded the corresponding furo[2,3-d]pyrimidine-2,4(1H,3H)-diones in 1-butyl-3-methylimidazolium bromide as an ionic liquid in high yields at room temperature within several minutes.     

Mercaptan addition to 1-<Emphasis Type="Italic">O</Emphasis>-allyl-2,3,4,6-tetra-<Emphasis Type="Italic">O</Emphasis>-acetyl-<Emphasis Type="Italic">β</Emphasis>-D-galactopyranose

Addition of ethyl-, propyl-, and n-butylmercaptans to 1-O-allyl-2,3,4,6-tetra-O-acetyl-β-D-galactopyranose in the presence of benzoyl peroxide catalyst was studied for the first time. The products were 1-O-(3-ethylthiopropyl)-2,3,4,6-tetra-O-acetyl-β-D-galactopyranose, 1-O-(3-propylthiopropyl)-2,3,4,6-tetra-O-acetyl-β-D-galactopyranose, and 1-O-(3-butylthiopropyl)-2,3,4,6-tetra-O-acetyl-β-D-galactopyranose. Deacetylation of 1-O-(3-ethylthiopropyl)-2,3,4,6-tetra-O-acetyl-β-D-galactopyranose produced 1-O-(3-ethylthiopropyl)-β-D-galactopyranose. __________ Translated from Khimiya Prirodnykh Soedinenii, No. 3, pp. 209–211, May–June, 2007.     

New Benzo[<Emphasis Type="Italic">b</Emphasis>]xanthones from Diels-Alder Reactions of Chromone-3-carboxaldehydes with <Emphasis Type="Italic">ortho</Emphasis>-Benzoquinodimethanes

Summary.  New benzo[b]xanthone derivatives, having substituents in the A and D rings, were prepared from cycloaddition reactions of chromone-3-carboxaldehydes with ortho-benzoquinodimethanes, generated in situ from 1,3-dihydrobenzo[c]thiophene 2,2-dioxide, followed by oxidation of the obtained diastereomeric adducts. The structure of all compounds was fully established by 1D and 2D NMR, MS, and elemental analysis. The stereochemistry of the obtained diastereomeric cycloadducts was established by NOESY experiments. Corresponding author. E-mail: arturs@dq.ua.pt Received September 16, 2002; accepted September 20, 2002     

Synthesis and properties of <Emphasis Type="Italic">N</Emphasis>-[2,2-bis(2,4-dihydroxyaryl)ethyl]-<Emphasis Type="Italic">N</Emphasis>-methylamines and their hydrohalides

Condensation of one molecule of α-methylaminoacetaldehyde dimethyl acetal with two molecules of resorcinol or methylresorcinol in hydrohalogen acid solutions led to substituted N-(2,2-diarylethyl)-N-methylamine hydrohalides. Reactions of the corresponding amines with acetic anhydride, mono-and diisocyanates, and formaldehyde were studied. Conditions for formation of calixarene from resorcinol and α-methylaminoacetaldehyde dimethyl acetal were invented. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 2, pp. 319–324, February, 2007.     

Synthesis of 2,3-<Emphasis Type="Italic">cis</Emphasis> Stereomeric Emetamines <Emphasis Type="Italic">via Reissert</Emphasis> Compounds

Summary. Alkylation of Reissert compounds with certain benzoquinolizinone derivatives followed by hydrolytic cleavage afforded the core of the title compounds in a two step sequence. Finally, the lactam intermediates were reduced with DIBAH giving the target compounds, the structural and stereochemical assignments of which were achieved by ¹³C NMR spectroscopy. Part of PhD thesis, LMU München, D     

Structure and photochromism of 2-(<Emphasis Type="Italic">N</Emphasis>-acyl-<Emphasis Type="Italic">N</Emphasis>-arylaminomethylene)benzo[<Emphasis Type="Italic">b</Emphasis>]thiophen-3(2<Emphasis Type="Italic">H</Emphasis>)-ones

It was shown by electron absorption spectroscopy and X-ray diffraction analysis that steric strains in photochromic 2-(N-acyl-N-arylaminomethylene) benzo[b]thiophen-3(2H)-one molecules ortho-substituted in the N-phenyl ring increase the quantum yield of the N→O photoinduced rearrangement in accord with an increase in the steric constant of the ortho-substituent.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2151–2155, October, 2004.     

Phosphorylation of Per-6-<Emphasis Type="Italic">O</Emphasis>-[(<Emphasis Type="Italic">tert</Emphasis>-butyl)dimethylsilyl]-β-cyclodextrin with Tetraethylphosphorodiamidochloridite

Phosphorylation of β-cyclodextrin with protected primary hydroxy groups with tetraethylphosphorodiamidochloridite, contrary to phosphorylation with hexaethylphosphorous triamide, proceeds irregularly and leads to compounds with mixed functions, whose ratio depends on reaction conditions.     

On the Synthesis of Pyrrolobenzo[<Emphasis Type="Italic">b</Emphasis>]thieno[1,4]diazepines

Summary. 2-Amino-4,5,6,7-tetrahydrobenzo[b]thiophene-3-carbonitrile was converted into the corresponding 2-(pyrrol-1-yl) derivative, followed by reduction of the latter compound into the corresponding amine. This amine and its acyl, aroyl, and arylidene derivatives were used as synthons in the synthesis of several title compounds.     

Synthesis and properties of pyrimido[4,5-<Emphasis Type="Italic">a</Emphasis>]- and pyrido[4,3-<Emphasis Type="Italic">a</Emphasis>]carbazole derivatives

Methods for the synthesis of substituted pyrimido [4,5-a]- and pyrido[4,3-a]carbazoles were proposed. Condensation of 2-(dimethylaminomethylene)-6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-one with guanidine and thiourea afforded 2-amino-8-methyl-6,11-dihydro-5H-pyrimido[4,5-a]carbazole and 8-methyl-3,5,6,11-tetrahydro-2H-pyrimido[4,5-a]carbazole-2-thione, respectively. The reaction of cyano(6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-ylidene)acetamide with dimethylformamide dimethyl acetal gave N-(dimethylamino-methylene)cyano(6-methyl-2,3,4,9-tetrahydro-1H-carbazol-1-ylidene)acetamide. Cyclization of the latter yielded 1-cyano-8-methyl-3,5,6,11-tetrahydro-2H-pyrido[4,3-a]carbazol-2-one.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2740–2744, December, 2004.     

Synthesis of 6-aryl-1,6-dihydrodipyrazolo[3,4-<Emphasis Type="Italic">b</Emphasis>:4,3-<Emphasis Type="Italic">c</Emphasis>]pyridines

6-Azido-1H-pyrazolo[3,4-b]pyridino-5-carbaldehydes react with aromatic amines to give the corresponding N-arylimines which cyclize on heating in boiling toluene to give 6-aryl-1,6-dihydrodipyrazolo[3,4-b:4,3-e]pyridines.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 11, 1717–1722, November, 2004.     

3,3,3-Trifluoro-<Emphasis Type="Italic">N</Emphasis>′-(3-trifluoromethylphenyl)-1,2-propanediamine and its <Emphasis Type="Italic">N</Emphasis>-mono-and <Emphasis Type="Italic">N,N</Emphasis>-dicarboxyethyl derivatives: synthesis,protolytic and complexation properties

3,3,3-Trifluoro-N′-(3-trifluoromethylphenyl)-1,2-propanediamine (5) was synthesized by the reaction of 2-diazo-1,1,1-trifluoro-3-nitropropane or 3,3,3-trifluoro-1-nitropropene with 3-aminobenzotrifluoride followed by the reduction of the nitro group. The Michael 1,4-addition of diamine 5 to acrylic acid occurs only at the N(1) atom and affords N-mono-or N,N-dicarboxyethyl derivatives 6 and 7, depending on the reactant ratio. Protolytic equilibria 5–7 in aqueous solutions were studied by pH-potentiometry and UV spectroscopy. Only the aliphatic amino group can be protonated in an aqueous solution, while the aromatic amino group remains unprotonated even in 12 M HCl. The stability constants of transition metal (Cu²⁺, Ni²⁺, Zn²⁺) complexes with ligands 5–7 were determined by pH-potentiometric titration. The stability of the complexes and selectivity of the ligands toward Cu²⁺ ions increase with an increase in the number of N-carboxyethyl groups. Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 11, pp. 2465–2469, November, 2005.     

Carboxylic Acids from <Emphasis Type="Italic">Phyllanthus urinaria</Emphasis>

Five compounds, terephthalic acid mono-[2-(4-carboxy-phenoxycarbonyl)-vinyl] ester (1), (E)-3-(5′-hydroperoxy-2,2′-dihydroxy[1,1′-biphenyl]-4-yl)-2-propenoic acid (2), 3,4,5-trihydroxybenzoic acid (3), succinic acid (or butanedioic acid) (4), and 2,3,4,5,6-pentahydroxybenzoic acid (5), were isolated from Phyllanthus urinaria. The structures of these compounds were elucidated by means of spectral techniques including IR, MS, and 1D/2D NMR. 1 and 2 are new compounds.__________Published in Khimiya Prirodnykh Soedinenii, No. 1, pp. 14–17, January–February, 2005.