Studies on uracil derivatives and analogs. Syntheses of 5-(βt-trimethylsilyl)ethynyluracil and 5-ethynyluracil

5-(α-Chlorovinyl)-2,4-dichloropyrimidine (I) on treatment with sodium methoxide in methanol was converted to 2,4-dimethoxy-5-ethynylpyrimidine (II) which was silylated by t-butyl lithium and chlorotrimethylsilane to 2,4-dimethoxy-5-β-trimethylsilyl)ethynylpyrimidine (IV). Compound IV on deblocking with trimethylsilyl iodide yielded 5-(β-trimethylsilyl)ethynyluracil (V), which on treatment with sodium hydroxide in methanol was converted to 5-ethynyluracil (VI).     

The stereochemistry of myxothiazol

The absolute configuration of myxothiazol is established as 4(6-carbamoyl-3S,5-dimethoxy-4R-methylhexa-1E,5E-dienyl)-2′-(1S ,6-dimethylhepta-2E,4E-dienyl)-2,4′-bithiazole by a combination of chemical methods and X-ray analysis     

The route of action of sodium methoxide on 5-Arylmethylene-2-Disubstituted amino-4-oxo-2-thiazolines

5-Arylmethylene-2-disubstituted amino-4-oxo-2-thiazolines 1a-d reacted with six and two moles of sodium methoxide to give the 2-mercaptocinnamic acid esters 6 and mixtures of 2,2 -dimethoxy-4-oxothiazolidines 4 and 2,4-dioxothiazolidines 5 , respectively. The intermediate mixture of the sodium salt of 5-aryImethylene-2,2-dimethoxy-4-oxothiazolidines 3 in the above mentioned transofrmations was established. The structures of 3, 4, 5 and 6 were based on analytical and spectral evidence. The route of conversion of 1 into 3, 4,5 and 6 was presented and discussed.     

Fortuneanosides G-L, dibenzofuran glycosides from the fruit of Pyracantha fortuneana

Six new dibenzofuran glycosides, fortuneanosides G (1), H (2), I (3), J (4), K (5), and L (6), were isolated from the fruit of Pyracantha fortuneana (MAXIM) LI. Their structures were determined to be 3,7-dihydroxy-2,4-dimethoxy-dibenzofuran 7-O-beta-D-glucopyranoside, 3,7-dihydroxy-2,4-dimethoxy-dibenzofuran 7-O-(alpha-L-rhamnopyranosyl)-(1-6)-beta-D-glucopyranoside, 3,6-dihydroxy-2,4-dimethoxy-dibenzofuran 6-O-beta-D-glucopyranoside, 2,4-dimethoxy-3,6,9-trihydroxy-dibenzofuran 6-O-beta-D-glucopyranoside, 3,9-dihydroxy-2,4-dimethoxy-dibenzofuran 3-O-beta-D-glucopyranoside, and 2-methoxy-3,4,9-trihydroxy-dibenzofuran 4-O-beta-D-glucopyranoside based on spectroscopic analysis. Fortuneanosides G-J showed more potent tyrosinase-inhibitory activity than arbutin.     

Synthetic transformations of isoquinoline alkaloids. Synthesis of 1-halo derivatives of <Emphasis Type="Italic">endo</Emphasis>-ethenotetrahydrothebaine and their behavior in the heck reaction

Bromination of endo-ethenotetrahydrothebaine derivatives having a pyrrolidine ring fused at the C⁷-C⁸ bond, namely 1′-substituted 4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinan-2′,5′-diones, 1′-aryl-4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinans, and 4,5α-epoxy-6α,14-etheno-2′α-hydroxy-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morpphinan-5′-one, with molecular bromine in formic acid smoothly afforded the corresponding 1-bromo derivatives. Iodination of 4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]-4,5α-epoxy-6α,14-etheno-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]-morphinan-2′,5′-dione with iodine(I) chloride gave 4,5α-epoxy-6α,14-etheno-1-iodo-3,6-dimethoxy-17-methyl-1′-phenyl-2′,5′,7β,8β-tetrahydro-1′H-14α-pyrrolo[3′,4′:7,8]morphinan-2′,5′-dione. The resulting 1-halo derivatives were brought into the Heck reaction with acrylic acid esters to obtain 1-[(E)-2-(alkoxycarbonyl)ethenyl]-substituted compounds. Demethylation of the 6-methoxy group in 1-bromo-endo-ethenotetrahydrothebaines was accomplished using boron(III) bromide in chloroform.     

s-Triazine derivatives. 3. Investigation of the reaction of chloromethoxy-s-triazines with CH acids

The condensation of 2-chloro-4,6-dimethoxy- and 2,4-dichloro-6-methoxy-s-triazines with sodium derivatives of ethyl esters of acetoacetic and cyanoacetic acids and malonodinitrile was investigated. 2-Dicyanomethylene-4,6-dimethoxy-1,2-dihydro-, 2-carbethoxycyanomethylene-4,6-dimethoxy-1,2-dihydro-, and 2,4-bis(carbethoxy-methylene)-6-methoxy-1,2,3,4-tetrahydro-s-triazines were obtained in high yields.See [1] for Communication 2.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 264–267, February, 1981.     

Synthesis of 5′-azido- and 5′-amino-2′,5′-dideoxynucleosides from quinazoline-2,4(1H,3H)-diones

Quinazoline-2,4(1H,3H)-diones 4 were silylated and condensed with methyl 5-azido-2,5-dideoxy-3-O-(4-methylbenzoyl)-α,β-D-erythro-pentofuranoside (3) using trimethylsilyl trifluoromethanesulfonate (TMS triflate) as the catalyst to afford the corresponding 5′-azidonucleosides 5 . 1-(5-Azido-2,5-dideoxy-α-D-erythro-pentofuranosyl)quinazoline-2,4(1H,3H)-diones 6 and the corresponding β anomers were obtained by treating 5 with sodium methoxide in methanol at room temperature. 6-Methyl-1-(5-amino-2,5-dideoxy-β-D-erythro-pentofuranosyl)quinazoline-2,4(1H,3H)-dione (8) was obtained by treatment of the corresponding azido derivative 7 with triphenylphosphine in pyridine, followed by hydrolysis with ammonium hydroxide.     

A novel approach to the synthesis of 6-substituted uracils in three-step, one-pot reactions

From the commercial 6-chloro-2,4-dimethoxypyrimidine (1) and by a photostimulated reaction with Me(3)Sn(-) ions, 2,4-dimethoxy-6-(trimethylstannyl)pyrimidine (2) was obtained in 95% yield. By the cross-coupling reaction of 2 with 1-iodonaphthalene as electrophile catalyzed by Pd (Stille reaction), 2,4-dimethoxy-6-(naphthalen-1-yl)pyrimidine (9) was obtained in 76% yield. By hydrolysis of 9, 6-(1-naphthyl)uracil was obtained in 98% of isolated yield. When the three steps (S(RN)1 reaction-cross coupling reaction-hydrolysis) were performed in a one-pot reaction, 6-substituted uracils (1-naphthyl, 4-chlorophenyl, 3-chlorophenyl, 2,3,4,5,6-pentafluorophenyl) were obtained (43-57%) of isolated pure products. When the electrophile was a benzoyl chloride, 6-benzoyl uracil (54%) and 6-(2-chlorobenzoyl) uracil (49%) were obtained in isolated pure products.     

两种新木脂素(±)-Eusiderin E和(±)-Eusiderin F的全合成研究

以焦性没食子酸为原料 ,以克来森重排为关键步骤 ,首次合成了天然产物 (± ) -Eusiderin E和 (± ) -Eusiderin F     

A reinvestigation of the structures for 5-diazouracil, 5-diazouridine, 5-diazo-2′-deoxyuridine and certain related derivatives by proton magnetic resonance spectroscopy

The structure of 5-diazouracil and several closely related derivatives have been revised on the basis of pmr spectroscopy. 5-Diazouracil, 5-diazouracil hydrate, 5-diazouracil methanol adduct, 5-diazouridine and 5-diazo-2′-deoxyuridine have been reassigned the structures 5-diazopyrimidin-2,4(3H)dione (XI), 5-diazo-6-hydroxy-1,6-dihydropyrimidin-2,4(1H,3H,6H)dione (XIII), 5-diazo-6-methoxy-1,6-dihydropyrimidin-2,4(1H,3H,6H)dione (XII), 1 -(β-D-ribofuranosyl)-O^5′ -6(S)cyclo-5-diazo-1,6-dihydropyrimidin-2,4(3H,6H)dione (XVII) and 1-(2-deoxy-β-D-ribofuranosyl)-O^5′ -6(S)cyclo-5-diazo-1,6-dihydropyrimidin-2,4(3H,6H)dione (XIX), respectively. Treatment of XII with dimethylamine resulted in a coupling of the 5-diazo group with dimethylamine and a concomitant rearomatization of the heterocyclic ring by expulsion of the 6-methoxy group to furnish 5-(3,3-dimethyl-1-triazeno)uracil (XIV). A similar reaction of XIX and XVII with dimethylamine furnished the corresponding 5-(3,3-dimethyl-1-triazeno)derivatives. The effect which certain resonance hybrids of the diazo moiety may exert in reactions of the above hetero-cycles and the assignment of S configuration at C-6 for the nucleoside derivatives is also discussed.     

A Facile Synthesis of Ethyl 2,4-Dimethoxy-6-perfluoroalkyl-benzoates via Acyclic Precursors

Introduction Polysubstituted arenes are important intermediates in synthetic medicines and dyestuffs, and the fluorinated analogues are more attractive as a result of their lipo-philicity and the increment of activity.1,2 Therefore, to study the convenient and efficient synthesis of polysub-stituted arenes is valuable in organic synthetic method-ology. We have designed a simple synthesis of fluori-nated polysubstituted arenes through the intramolecular Wittig reaction of a new phosphorous ylid…     

A convenient synthesis of 2′-deoxy-6-thioguanosine,ara-guanine,ara-6-thioguanine and certain related purine nucleosides by the stereospecific sodium salt glycosylation procedure

A simple and high-yield synthesis of biologically significant 2′-deoxy-6-thioguanosine ( 11 ), ara-6-thioguanine ( 16 ) and araG ( 17 ) has been accomplished employing the Stereospecific sodium salt glycosylation method. Glycosylation of the sodium salt of 6-chloro- and 2-amino-6-chloropurine ( 1 and 2 , respectively) with 1-chloro-2-deoxy-3,5-di-O-(p-toluoyl)-α-D-erythro-pentofuranose ( 3 ) gave the corresponding N-9 substituted nucleosides as major products with the β-anomeric configuration ( 4 and 5 , respectively) along with a minor amount of the N-7 positional isomers ( 6 and 7 ). Treatment of 4 with hydrogen sulfide in methanol containing sodium methoxide gave 2′-deoxy-6-thioinosine ( 10 ) in 93% yield. Similarly, 5 was transformed into 2′-deoxy-6-thioguanosine (β-TGdR, 11 ) in 71 % yield. Reaction of the sodium salt of 2 with 1-chloro-2,3,5-tri-O-benzyl-α-D-arabinofuranose ( 8 ) gave N-7 and N-9 glycosylated products 13 and 9 , respectively. Debenzylation of 9 with boron trichloride at ?78° gave the versatile intermediate 2-amino-6-chloro-9-β-D-arabinofuranosyl-purine ( 14 ) in 62% yield. Direct treatment of 14 with sodium hydrosulfide furnished ara-6-thioguanine ( 16 ). Alkaline hydrolysis of 14 readily gave 9-β-D-arabinofuranosylguanine (araG, 17 ), which on subsequent phosphorylation with phosphorus oxychloride in trimethyl phosphate afforded araG 5′-monophosphate ( 18 ).     

The synthesis of 3-deazapyrimidine nucleosides related to uridine and cytidine and their derivatives

Condensation of 2,4-bis(trimethylsilyloxy)pyridine ( 1 ) with 2,3,5-tri-O-benzoyl-D-ribofuranosyl bromide ( 2 ) gave 4-hydroxy-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2-pyridone ( 3 ). Deblocking of 3 gave 4-hydroxy-1-β-D-ribofuranosyl-2-pyridone (3′-deazauridine) ( 4 ). Treatment of 4 with acetone and acid gave 2′,3′-O-isopropylidene-3-deazauridine ( 6 ). Reaction of 4 with diphenylcarbonate gave 2-hydroxy-1-β-D-arabinofuranosyl-4-pyridone-O₂←2′-cyclonucleoside ( 7 ) which established the point of gylcosidation and configuration of 4 . Base-catalyzed hydrolysis of 7 gave 4-hydroxy-1-β-D-arabinofuranosyl-2-pyridone (3-deazauracil arabinoside) ( 12 ). Fusion of 1 with 3,5-di-O-p-toluyl-2-deoxy-D-erythro-pentofuranosyl chloride ( 5 ) gave the blocked anomeric deoxynucleosides 8 and 10 which were saponified to give 4-hydroxy-1-(2-deoxy-β-D-erythro-pentofuranosyl)-2-pyridone (2′-deoxy-3-deazauridine) ( 11 ) and its α anomer ( 9 ). Condensation of 4-acetamido-2-methoxypridine ( 13 ) with 2 gave 4-acetamido-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2-pyridone ( 14 ) which was treated with alcoholic ammonia to yield 4-acetamido-1-β-D-ribofuranosyl-2-pyridone ( 15 ) or with methanolic sodium methoxide to yield 4-amino-1-β-D-ribofuranosyl-2-pyridone (3-deazacytidine) ( 16 ). Condensation of 13 and 2,3,5-tri-O-benzyl-D-arabinofuranosyl chloride ( 17 ) gave the blocked nucleoside 22 which was treated with base and then hydrogenolyzed to give 4-amino-1-β-D-arabinofuranosyl-2-pyridone (3-deazacytosine arabinoside) ( 23 ). Fusion of 13 with 5 gave the blocked anomeric deoxynucleosides 18 and 20 which were deblocked with methanolic sodium methoxide to yield 4-amino-1-(2-deoxy-β-D-erythro-pentofuranosyl)-2-pyridone (2′-deoxy-3-deazacytidine) ( 21 ) and its a anomer 19 . The 2′-deoxy-erythro-pentofuranosides of both 3-deazauracil and 3-deazacytosine failed to obey Hudson's isorotation rule but did follow the “quartet”-“triplet” anomeric proton splitting pattern in the ¹H nmr spectra.     

Synthesis of 1-(3′-deoxy-β-D-glycero-pentofuran-2′-ulosyl)uracil by selective elimination reactions

For the synthesis of y 1-(3′-deoxy-β-D-glycero-pentofuran-2′-ulosyl)uracil (16), the precursor, 5′-O-benzoyl derivative (2),² was elaborated in a variety of ways. 1-(5′-O-Benzoyl-3′-O-tosyl-β-D- lyxofuranosyl)uracil (4)² was benzoylated to N³-benzoyl-1-(2′,5′-di-O-benzoyl-3′-O-tosyl-β-D- lyxofuranosyl)uracil (5), which directly yielded 2 on treatment with sodium benzoate. 1-(3′,5′-Di-O- benzoyl-2′-O-tosyl-β-D-lyxofuranosyl)uracil (8) and its 3′,5′-O-isopropylidene analog (10) resisted elimination reactions, thus proving absolute selectivity in the elimination of the derivatives of 1-β-D- lyxofuranosyl-uracil. Seeking a more economical path to 2, 1-(5′-O-benzoyl-β-D-lyxofuranosyl)uracil (11) was first benzoylated to give 2′,5′-di-O-benzoate (12), accompanied by 3′,5′-di- and 2′,3′,5′-tri-O- benzoate. Mesylation of the major product (12) gave 1-(2′,5′-di-O-benzoyl-3′-O-mesyl-β-D- lyxofuranosyl)uracil (15), which, on treatment with sodium benzoate, gave 2 in an highly improved yield. Basic hydrolysis on 2 gave compound 16.     

Novel and versatile reactions of trifluoroamine oxide: a new route to polyfluorinated ethers

A series of pyrimidine methyl and polyfluoroalkyl ethers were synthesized from the reactions of trifluoroamine oxide (1) with several 5-substituted uracils in the presence of tetrabutylammonium hydroxide and methanol, 2,2,2-trifluoroethanol (6), or 1H,1H-pentafluoropropanol (7). With 5-(trifluoromethyl)uracil (2), the new ethers formed were 5-fluoro-5-(trifluoromethyl)-6-methoxypyrimidine-2,4-dione (8), 5-fluoro-5-(trifluoromethyl)-6-(trifluoroethoxy)pyrimidine-2,4-dione (9), and 5-fluoro-5-(trifluoromethyl)-6-(1H,1H- pentafluoropropoxy)pyrimidine-2,4-dione (10). With 5-chlorouracil (3), the new ethers 5-chloro-5-fluoro-6-methoxypyrimidine-2,4-dione (11), 5-chloro-5-fluoro-6-(trifluoroethoxy)pyrimidine-2,4-dione (12), and 5-chloro-5-fluoro-6-(1H,1H-pentafluoropropoxy)pyrimidine-2,4-dione (13) were obtained. With 5-fluorouracil (4), the new ethers 5,5-difluoro-6-methoxypyrimidine-2,4-dione (14), 5,5-difluoro-6-(trifluoroethoxy)pyrimidine-2,4-dione (15) and 5,5 difluoro-6-(1H,1H-pentafluoropropoxy)pyrimidine-2,4-dione (16) were found. By reaction of 5-nitrouracil (5), the new ethers 5-nitro-5-fluoro-6 methoxypyrimidine-2,4-dione (17), 5-nitro-5-fluoro-6-(trifluoroethoxy)pyrimidine-2,4-dione (18), and 5-nitro-5-fluoro-6-(1H,1H-pentafluoropropoxy)pyrimidine-2,4-dione (19) were obtained. Each of the new compounds was characterized by using IR, 19F and 1H NMR, and mass spectroscopy, and elemental analysis. A single-crystal X-ray diffraction study of 8 was helpful in confirming compound structure.     

Eine neue Synthese von 8-Hydroxy-2-methyl-1,2,3,4-tetrahydroisochinolin

A new Synthesis of 8-Hydroxy-2-methyl-1,2,3,4-tetrahydroisoquinoline Vilsmeier formylation of N-[2-(3,5-dimethoxyphenyl)ethyl]-trifluoroacetamide ( 5 ) yielded the aldehyde 6 , which under mild basic conditions was hydrolyzed to 7 and cyclized to 6,8-dimethoxy-3,4-dihydroisoquinoline ( 3 ). Methylation of 3 and reduction of the double bond in 10 afforded 6,8-dimethoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline ( 11 ). The methoxyl group at C(6) was selectively demethylated and the free hydroxyl group in 12 was phosphorylated to give 13 . Reduction of the latter with potassium in liquid ammonia yielded 8-methoxy-2-methyl-1,2,3,4-tetrahydroisoquinoline ( 2 ), which was demethylated to the title compound 1 .     

MEH-PPV型单体[2,5-双(4′-溴-2′,5′-二甲氧基苯基乙烯基)-1-甲氧基-4-(2′-乙基己基氧基)苯]的合成及其发光性能

以对苯二甲醚为原料,经甲酰化和溴代反应合成2,5-二甲氧基-4-溴苯甲醛(2)。以对甲氧基苯酚为原料,经烷基化、氯甲基化和Michaelis-Arbuzov反应合成亚膦酸酯(5);2和5经Horner-Wittig-Emmons反应合成了2,5-双(4′-溴-2′,5′-二甲氧基苯基乙烯基)-1-甲氧基-4-(2′-乙基己基氧基)苯(6),总收率44.7%,其结构经1HNMR,13C NMR和元素分析表征。UV-Vis和荧光光谱(FL)研究表明,6的UV-Vis和FL的λmax分别位于410 nm和479 nm,497 nm,是一种绿光的MEH-PPV型单体。     

Synthesen von enantiomerenreinen Apoviolaxanthin-säuren, -olen und -alen (Persicaxanthin,Sinensiaxanthin und β-Citraurin-epoxid) und ihrer furanoiden Umlagerungsprodukte

Synthesis of Enantiomerically Pure Apoviolaxanthinoic Acids, Apoviolaxanthinols, and Apoviolaxanthinals (Including Persicaxanthin, Sinensiaxanthin, and β-Citraurin Epoxide) and of their Furanoid Rearrangement Products Starting from (1′S,2′R,4′S,2E,4E)-5-(1′,2′-epoxy-4′-hydroxy-2′,6′,6′-trimethylcyclohexy1)-3-methy1-2,4-pentadienal ( 3 ), a recently described synthon [6], a full range of C₂₀-, C₂₅-, C₂₇-, and C₃₀-polyenic acids, alcohols, and aldehydes and their (8R)- and (8S)-diastereoisomeric furanoid rearrangement products was prepared. The synthetic C₂₅-alcohols proved to be identical with persicaxanthin (= 12′-apoviolaxanthin-12′-ol) and perisicachromes (= 12′-apoauroxanthin-12′-ols) and the C₂₇-alcohols analogously with sinensiaxanthin and sinensiachromes. A correlation between the sign of the Cotton effects in the CD spectra of 5,6-and 5,8-epoxides and their configuration at C(6) and C(8), respectively, was established.     

Synthesis of 7-alkyl-2,4-dimethoxy-5-oxo-5H-pyrano[4,3-d]pyrimidines

A convenient synthesis of 7-alkyl-2,4-dimethoxy-5-oxo-5H-pyrano[4,3-d]pyrimidines from methyl 2,4-dimethoxy-6-phenylselenylmethyl (or 6-phenylthiomethyl)-5-pyrimidinecarboxylate with alkylaldehydes is described.