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Papers by Werner Bussmann
ABSTRACT Paderborn, Univ., Diss., 1984.
Tetrahedron, 1985
ABSTRACT 2'-Deoxy-1-deazawyosine (3a), an isostere of the rare tRNA constituent wyosine (... more ABSTRACT 2'-Deoxy-1-deazawyosine (3a), an isostere of the rare tRNA constituent wyosine (la) and its α-anomer have been synthesized via glycosylation of the nucleobase 5a with the halogenose 6. In contrast to the labile parent 1a, the isostere is highly stabile against hydrolysis even as 2'-deoxynuclcoside. The stability of 3a is due to the low susceptibility of the pyrrol ring to protonation. The rapid hydrolysis of wyosine (la) compared to guanosine is explained by a favoured solvatization of the molecule being freezed in the anti-conformation.
Journal of Medicinal Chemistry
The N-methyl isomers of 2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (2a) have been synth... more The N-methyl isomers of 2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (2a) have been synthesized regiospecifically and their structures assigned. The 3-methyl compound 3 was obtained by alkylation of the parent chromophore 2a with dimethyl sulfate, and the 1-methyl isomer 5b was obtained by condensation of ethyl 2-cyano-4,4-diethoxybutyrate with N-methylguanidine and subsequent cyclization. Methylation of 2-amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (7b), however, with methyl iodide in the presence of 50% NaOH, by phase-transfer techniques, followed by the replacement of halide by hydroxyl, yielded the 7-methyl compound 2b. The N-methyl isomers of 2a were all found to be inhibitors of xanthine oxidase from cow's milk. While the 3-methyl isomer 3 exhibits a Ki of 40 microM, the 7- and 1-isomers show Ki values of 4.5 and 3 microM, respectively.
![Research paper thumbnail of Die isomeren 4-Amino-N-methylpyrrolo[2,3-d]pyrimidine](https://attachments.academia-assets.com/48372435/thumbnails/1.jpg)
](European Journal of Inorganic Chemistry, 1981
Die Methylierung von 4-Amino-7H-pyrrolo[2,3,-d]pyrimidin (2a) führt im Neutralen zu einer 1: 1-Mi... more Die Methylierung von 4-Amino-7H-pyrrolo[2,3,-d]pyrimidin (2a) führt im Neutralen zu einer 1: 1-Mischung der N-1-(6a) und N-3-Isomeren 5a). Die Konstitutionszuordnung erfolgte durch Dimroth-Umlagerung von 5a zu 2e. Das Isomer 6a kann auch durch Entschwefelung des Thioderivates 4a erhalten werden; letzteres überwiegt (3:1) bei der Cyclisierung des Pyrimidin-Derivates 3. Die selektive N-7-Methylierung von 2a bzw. 2b erfolgte durch Phasentransfermethylierung im alkalischen Medium.The Isomeric 4-Amino-N-methylpyrrolo[2,3-d]pyrimidinesMethylation of 4-amino-7H-pyrrolo[2,3-d]pyrimidine (2a) (neutral conditions) leads to a 1:1 mixture of N-1 (6a) and N-3 isomers (5a). The structural assignment was accomplished by Dimroth rearrangement of 5a yielding 2e. The isomer 6a is also obtained by desulfurisation of the thio derivative 4a; the latter predominates (3:1) in cyclisation of the pyrimidine derivative 3. Selective N-7 methylation of 2a or 2b was achieved by phase transfer methylation under alkaline conditions.
European Journal of Organic Chemistry, 1984
Die anomeren 2-(Methylthio)tubercidine 1 und 2 wurden aus den Chlornucleosiden 3a und 4a dargeste... more Die anomeren 2-(Methylthio)tubercidine 1 und 2 wurden aus den Chlornucleosiden 3a und 4a dargestellt und zu Tubercidin (3c) und seinem α-Anomer 4c entschwefelt. Die Entschwefelung der (Δ2-Isopentenyl)verbindungen 3b und 4b führt zu 3d und 4d sowie teilweise unter Reduktion zu 3e und 4e. N4-(Δ2-Isopentenyl)tubercidin (3d) ist auch durch Isopentenylierung von Tubercidin nach Dimroth-Umlagerung zugänglich. Die 1J(C,H)-Kopplungen des glyconischen Restes führen zur Zuordnung der 13C-Signale beim α-Anomeren 2 und die 3J(C-6,1′-H)-Kopplung zum Torsionswinkel χ, der bei den Tubercidinen im anti-Bereich liegt.Anomers of Tubercidin Derivatives with 2-Methylthio and N4-(Δ2-Isopentenyl) ResiduesStarting with the chloronucleosides 3a and 4a the anomers 1 and 2 or 2-(methylthio)tubercidin were prepared. They are desulfurized to tubercidin (3c) and its α-anomer 4c. Desulfurization of the N4-(Δ2-isopentenyl) compounds 3b and 4b yields 3d and 4d; due to hydrogenation the by-products 3e and 4e are formed. Isopentenylation of tubercidin followed by Dimroth rearrangement also give N4-(Δ2-isopentenyl)tubericidin (3d). From the 1J(C,H) coupling constants of the glyconic moiety the sequence of the 13C signals of the α-anomer 2 was deduced. The 3J(C-6,1′-H) couplings of tubercidins gave the torsion angle χ which is found to be in the anti region.
European Journal of Organic Chemistry, 1982
Die Methylierung von 3,7-Dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-on (1a) oder seines 2-Methylthioder... more Die Methylierung von 3,7-Dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-on (1a) oder seines 2-Methylthioderivates mit Dimethylsulfat führt im alkalischen Medium bevorzugt zu den N-3-Methyl-Derivaten 2a bzw. 2b. Das N-Isomer 3 wird hingegen durch Kondensation von 2-Cyan-4,4-diethoxybuttersäure-ethylester mit N-(Methyl)thioharnstoff über das Pyrimidinderivat 4a durch Cyclisierung zu 5a und anschließende Desulfurierung erhalten. Phasentransfer-Methylierung von 4-Methoxy-2-methylthio-7H-pyrrolo[2,3-d]pyrimidin führt zu 8a, aus dem durch Etherspaltung und Entschwefelung das N-7-Methylisomer 8c entsteht.Regioselective Synthesis of the N-Monomethyl Derivatives of 7-DeazahypoxanthineMethylation of 3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (1a) or its 2-methylthio derivative with dimethyl sulfate in alkaline solution leads preferentially to the 3-methyl derivatives 2a or 2b, respectively. The N-1 isomer 3, however, is obtained by condensation of ethyl 2-cyano-4,4-diethoxybutyrate with N-(methyl)thiourea via the pyrimidine 4a which after cyclisation to 5a was desulfurised to 3. Phase-transfer methylation of 4-methoxy-2-methylthio-7H-pyrrolo[2,3-d] pyrimidine furnishes 8a which after ether cleavage and desulfurisation gave the N-7-methyl isomer 8c.
Nucleosides Nucleotides & Nucleic Acids, 1982
ABSTRACT Phase-transfer catalysis of pyrrolo[2,3-d]pyrimidine 4a with the halogenose 5 yields the... more ABSTRACT Phase-transfer catalysis of pyrrolo[2,3-d]pyrimidine 4a with the halogenose 5 yields the anomers 6a and 7a. Deprotection with boron trichloride gives the chloro nucleosides 6b and 7b, which are converted into the potential anticytokinin 2 and its α-anomer 3.
Nucleosides Nucleotides & Nucleic Acids, 1984
Isopentenylation of 7-deazaadenine results in the formation of 7-deazatriacanthine (2a) and its c... more Isopentenylation of 7-deazaadenine results in the formation of 7-deazatriacanthine (2a) and its corresponding isomer 5a. Chromatographic separation was difficult, but after Dimroth rearrangement of 5a into the exocyclic compound 3a, 7-deazatricanthine could be isolated. Similiar to its parent purine compound, 3a cyclizes in the presence of strong acid to give the tricyclic system 4. NMR data reveal that 7-deazatriacanthine exists as the amino tautomer 2a. Protonation of N-1 alkyl-ated 7-deazaadenine occurs at N-7 to give compound 6 which exhibits restricted rotation of the amino group. The rotational barrier was determined from temperature dependent proton NMR spectra and found to be about 70 kJmol−1.
Journal of Medicinal Chemistry, 1984
The N-methyl isomers of 2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (2a) have been synth... more The N-methyl isomers of 2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (2a) have been synthesized regiospecifically and their structures assigned. The 3-methyl compound 3 was obtained by alkylation of the parent chromophore 2a with dimethyl sulfate, and the 1-methyl isomer 5b was obtained by condensation of ethyl 2-cyano-4,4-diethoxybutyrate with N-methylguanidine and subsequent cyclization. Methylation of 2-amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (7b), however, with methyl iodide in the presence of 50% NaOH, by phase-transfer techniques, followed by the replacement of halide by hydroxyl, yielded the 7-methyl compound 2b. The N-methyl isomers of 2a were all found to be inhibitors of xanthine oxidase from cow's milk. While the 3-methyl isomer 3 exhibits a Ki of 40 microM, the 7- and 1-isomers show Ki values of 4.5 and 3 microM, respectively.
Nucleosides Nucleotides & Nucleic Acids, 1985
The J(CH) coupling constant of C-1 in nucleosides is increased compared to those of the other car... more The J(CH) coupling constant of C-1 in nucleosides is increased compared to those of the other carbons of the sugar moiety. Applying this to several D-ribonucleosides the signals C-4′/C-1′of these a-anomers are reversed to those of the 8-counterparts (C-1′/C-4′). This phenomenon and the broadening of the C-3′ signal compared to that of C-2′ establishes the seauence C-4′,1′,2′,3′,5′ (increasing field) for
ABSTRACT Paderborn, Univ., Diss., 1984.
Tetrahedron, 1985
ABSTRACT 2'-Deoxy-1-deazawyosine (3a), an isostere of the rare tRNA constituent wyosine (... more ABSTRACT 2'-Deoxy-1-deazawyosine (3a), an isostere of the rare tRNA constituent wyosine (la) and its α-anomer have been synthesized via glycosylation of the nucleobase 5a with the halogenose 6. In contrast to the labile parent 1a, the isostere is highly stabile against hydrolysis even as 2'-deoxynuclcoside. The stability of 3a is due to the low susceptibility of the pyrrol ring to protonation. The rapid hydrolysis of wyosine (la) compared to guanosine is explained by a favoured solvatization of the molecule being freezed in the anti-conformation.
Journal of Medicinal Chemistry
The N-methyl isomers of 2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (2a) have been synth... more The N-methyl isomers of 2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (2a) have been synthesized regiospecifically and their structures assigned. The 3-methyl compound 3 was obtained by alkylation of the parent chromophore 2a with dimethyl sulfate, and the 1-methyl isomer 5b was obtained by condensation of ethyl 2-cyano-4,4-diethoxybutyrate with N-methylguanidine and subsequent cyclization. Methylation of 2-amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (7b), however, with methyl iodide in the presence of 50% NaOH, by phase-transfer techniques, followed by the replacement of halide by hydroxyl, yielded the 7-methyl compound 2b. The N-methyl isomers of 2a were all found to be inhibitors of xanthine oxidase from cow's milk. While the 3-methyl isomer 3 exhibits a Ki of 40 microM, the 7- and 1-isomers show Ki values of 4.5 and 3 microM, respectively.
European Journal of Inorganic Chemistry, 1981
Die Methylierung von 4-Amino-7H-pyrrolo[2,3,-d]pyrimidin (2a) führt im Neutralen zu einer 1: 1-Mi... more Die Methylierung von 4-Amino-7H-pyrrolo[2,3,-d]pyrimidin (2a) führt im Neutralen zu einer 1: 1-Mischung der N-1-(6a) und N-3-Isomeren 5a). Die Konstitutionszuordnung erfolgte durch Dimroth-Umlagerung von 5a zu 2e. Das Isomer 6a kann auch durch Entschwefelung des Thioderivates 4a erhalten werden; letzteres überwiegt (3:1) bei der Cyclisierung des Pyrimidin-Derivates 3. Die selektive N-7-Methylierung von 2a bzw. 2b erfolgte durch Phasentransfermethylierung im alkalischen Medium.The Isomeric 4-Amino-N-methylpyrrolo[2,3-d]pyrimidinesMethylation of 4-amino-7H-pyrrolo[2,3-d]pyrimidine (2a) (neutral conditions) leads to a 1:1 mixture of N-1 (6a) and N-3 isomers (5a). The structural assignment was accomplished by Dimroth rearrangement of 5a yielding 2e. The isomer 6a is also obtained by desulfurisation of the thio derivative 4a; the latter predominates (3:1) in cyclisation of the pyrimidine derivative 3. Selective N-7 methylation of 2a or 2b was achieved by phase transfer methylation under alkaline conditions.
European Journal of Organic Chemistry, 1984
Die anomeren 2-(Methylthio)tubercidine 1 und 2 wurden aus den Chlornucleosiden 3a und 4a dargeste... more Die anomeren 2-(Methylthio)tubercidine 1 und 2 wurden aus den Chlornucleosiden 3a und 4a dargestellt und zu Tubercidin (3c) und seinem α-Anomer 4c entschwefelt. Die Entschwefelung der (Δ2-Isopentenyl)verbindungen 3b und 4b führt zu 3d und 4d sowie teilweise unter Reduktion zu 3e und 4e. N4-(Δ2-Isopentenyl)tubercidin (3d) ist auch durch Isopentenylierung von Tubercidin nach Dimroth-Umlagerung zugänglich. Die 1J(C,H)-Kopplungen des glyconischen Restes führen zur Zuordnung der 13C-Signale beim α-Anomeren 2 und die 3J(C-6,1′-H)-Kopplung zum Torsionswinkel χ, der bei den Tubercidinen im anti-Bereich liegt.Anomers of Tubercidin Derivatives with 2-Methylthio and N4-(Δ2-Isopentenyl) ResiduesStarting with the chloronucleosides 3a and 4a the anomers 1 and 2 or 2-(methylthio)tubercidin were prepared. They are desulfurized to tubercidin (3c) and its α-anomer 4c. Desulfurization of the N4-(Δ2-isopentenyl) compounds 3b and 4b yields 3d and 4d; due to hydrogenation the by-products 3e and 4e are formed. Isopentenylation of tubercidin followed by Dimroth rearrangement also give N4-(Δ2-isopentenyl)tubericidin (3d). From the 1J(C,H) coupling constants of the glyconic moiety the sequence of the 13C signals of the α-anomer 2 was deduced. The 3J(C-6,1′-H) couplings of tubercidins gave the torsion angle χ which is found to be in the anti region.
European Journal of Organic Chemistry, 1982
Die Methylierung von 3,7-Dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-on (1a) oder seines 2-Methylthioder... more Die Methylierung von 3,7-Dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-on (1a) oder seines 2-Methylthioderivates mit Dimethylsulfat führt im alkalischen Medium bevorzugt zu den N-3-Methyl-Derivaten 2a bzw. 2b. Das N-Isomer 3 wird hingegen durch Kondensation von 2-Cyan-4,4-diethoxybuttersäure-ethylester mit N-(Methyl)thioharnstoff über das Pyrimidinderivat 4a durch Cyclisierung zu 5a und anschließende Desulfurierung erhalten. Phasentransfer-Methylierung von 4-Methoxy-2-methylthio-7H-pyrrolo[2,3-d]pyrimidin führt zu 8a, aus dem durch Etherspaltung und Entschwefelung das N-7-Methylisomer 8c entsteht.Regioselective Synthesis of the N-Monomethyl Derivatives of 7-DeazahypoxanthineMethylation of 3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (1a) or its 2-methylthio derivative with dimethyl sulfate in alkaline solution leads preferentially to the 3-methyl derivatives 2a or 2b, respectively. The N-1 isomer 3, however, is obtained by condensation of ethyl 2-cyano-4,4-diethoxybutyrate with N-(methyl)thiourea via the pyrimidine 4a which after cyclisation to 5a was desulfurised to 3. Phase-transfer methylation of 4-methoxy-2-methylthio-7H-pyrrolo[2,3-d] pyrimidine furnishes 8a which after ether cleavage and desulfurisation gave the N-7-methyl isomer 8c.
Nucleosides Nucleotides & Nucleic Acids, 1982
ABSTRACT Phase-transfer catalysis of pyrrolo[2,3-d]pyrimidine 4a with the halogenose 5 yields the... more ABSTRACT Phase-transfer catalysis of pyrrolo[2,3-d]pyrimidine 4a with the halogenose 5 yields the anomers 6a and 7a. Deprotection with boron trichloride gives the chloro nucleosides 6b and 7b, which are converted into the potential anticytokinin 2 and its α-anomer 3.
Nucleosides Nucleotides & Nucleic Acids, 1984
Isopentenylation of 7-deazaadenine results in the formation of 7-deazatriacanthine (2a) and its c... more Isopentenylation of 7-deazaadenine results in the formation of 7-deazatriacanthine (2a) and its corresponding isomer 5a. Chromatographic separation was difficult, but after Dimroth rearrangement of 5a into the exocyclic compound 3a, 7-deazatricanthine could be isolated. Similiar to its parent purine compound, 3a cyclizes in the presence of strong acid to give the tricyclic system 4. NMR data reveal that 7-deazatriacanthine exists as the amino tautomer 2a. Protonation of N-1 alkyl-ated 7-deazaadenine occurs at N-7 to give compound 6 which exhibits restricted rotation of the amino group. The rotational barrier was determined from temperature dependent proton NMR spectra and found to be about 70 kJmol−1.
Journal of Medicinal Chemistry, 1984
The N-methyl isomers of 2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (2a) have been synth... more The N-methyl isomers of 2-amino-3,7-dihydro-4H-pyrrolo[2,3-d]pyrimidin-4-one (2a) have been synthesized regiospecifically and their structures assigned. The 3-methyl compound 3 was obtained by alkylation of the parent chromophore 2a with dimethyl sulfate, and the 1-methyl isomer 5b was obtained by condensation of ethyl 2-cyano-4,4-diethoxybutyrate with N-methylguanidine and subsequent cyclization. Methylation of 2-amino-4-chloro-7H-pyrrolo[2,3-d]pyrimidine (7b), however, with methyl iodide in the presence of 50% NaOH, by phase-transfer techniques, followed by the replacement of halide by hydroxyl, yielded the 7-methyl compound 2b. The N-methyl isomers of 2a were all found to be inhibitors of xanthine oxidase from cow's milk. While the 3-methyl isomer 3 exhibits a Ki of 40 microM, the 7- and 1-isomers show Ki values of 4.5 and 3 microM, respectively.
Nucleosides Nucleotides & Nucleic Acids, 1985
The J(CH) coupling constant of C-1 in nucleosides is increased compared to those of the other car... more The J(CH) coupling constant of C-1 in nucleosides is increased compared to those of the other carbons of the sugar moiety. Applying this to several D-ribonucleosides the signals C-4′/C-1′of these a-anomers are reversed to those of the 8-counterparts (C-1′/C-4′). This phenomenon and the broadening of the C-3′ signal compared to that of C-2′ establishes the seauence C-4′,1′,2′,3′,5′ (increasing field) for