Studies on pyrazines. Part 37. Synthesis of 6-propionylpteridine-2,4(1H,3H)-dione and its 1- and/or 3-methyl derivatives from marine natural products

Sato, Nobuhiro; Fukuya, Shunsuke

doi:10.1039/a906572e

Cited by 11 publications

(7 citation statements)

References 18 publications

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“…The 6-chloro-(48) [19] and 7-chloro-1,3-dimethyllumazine (55) [19] are valuable starting materials which react Scheme 3 in the Pd-catalyzed reaction with phenylethyne and (trimethylsilyl)ethyne (¼ ethynyltrimethylsilane), respectively, in high yields to the corresponding 6-and 7substituted ethynyl derivatives 49 [17], 50 [20], 56, and 57 (Scheme 5), some of which have recently also been described by two other groups. Desilylation of 50 and 57 proceeded well by fluoride treatment to give 6-(51) and 7-ethynyl-1,3-dimethyllumazine (58).…”

Section: Methodsmentioning

confidence: 99%

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Pteridines. Part CXVII

Torigoe

Kariya

Soranaka

et al. 2007

Helvetica Chimica Acta

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A series of side chain reactions starting from the 6-and 7-styryl-substituted 1,3-dimethyllumazines 1 and 21 as well as from the 6-and 7-[2-(methoxycarbonyl)ethenyl]-substituted 1,3-dimethyllumazine 2 and 22 were performed first by addition of Br 2 to the C¼C bond forming the 1',2'-dibromo derivatives 3, 4, 24, and 26 in high yields (Schemes 1 and 3) (lumazine ¼ pteridine-2,4(1H,3H)-dione). Treatment of 3 with various nucleophiles gave rise to an unexpected tele-substitution in 7-position and elimination of the Br-atoms generating 7-alkoxy-(see 5 and 6), 7-hydroxy-(see 7) and 7-amino-6-styryl-1,3-dimethyllumazines (see 8 -11) (Scheme 1). On the other hand, 4 underwent, with dilute DBU (1,8-diazabicyclo[5.4.0]undec-2-ene), a normal HBr elimination in the side chain leading to 18, whereas treatment with MeONa afforded a more severe structural change to 19. Similarly, 24 and 26 reacted to 27, 32, and 33 under mild conditions, whereas in boiling NaOMe/MeOH, 24 gave 7-(2-dimethoxy-2-phenylethyl)-1,3dimethyllumazine (30) which was hydrolyzed to give 31 (Scheme 3). From the reactions of 4 and 24 with DBU resulted the dark violet substance 20 and 25, respectively, in which DBU was added to the side chain (Scheme 2). The styryl derivatives 1 and 21 could be converted, by a Sharpless dihydroxylation reaction, into the corresponding stereoisomeric 6-and 7-(1,2-dihydroxy-2-phenylethyl)-1,3-dimethyllumazines 34 -37 (Scheme 4). The dihydroxy compounds 34 and 35 were also acetylated to 38 and 39 which, on catalytic reduction followed by formylation, yielded the diastereoisomer mixtures 40 and 41. Deacetylation to 42 and 45 allowed the chromatographic separation of the diastereoisomers resulting in the isolation of 43 and 44 as well as 46 and 47, respectively. Introduction of a 6-or 7-ethynyl side chains proceeded well by a Sonogashira reaction with 6-(48) or 7-chloro-1,3-dimethyllumazine (55) yielding 49 -51 and 56 -58 (Scheme 5). The direction of H 2 O addition to the triple bond is depending on the substituents since the 6-(49) and 7-(phenylethynyl)-1,3-dimethyllumazine (56) showed attack at the 2'position yielding 53 and 60, in contrast to the 6-(51) and 7-ethynyl-1,3-dimethyllumazine (58) favoring attack at C(1') and formation of 6-(52) and 7-acetyl-1,3-dimethyllumazine (59).

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Section: Methodsmentioning

confidence: 99%

“…After neutralization with AcOH to pH 7 and evaporation, the residue was dissolved in H 2 O (20 ml) and extracted with CH 2 Cl 2 (2 Â 20 ml), and the org. phase dried (Na 2 SO 4 ) and concentrated: 0.26 g (77%) of 19 (20). To a soln.…”

Section: Experimental Partmentioning

confidence: 99%

Pteridines. Part CXVII

Torigoe

Kariya

Soranaka

et al. 2007

Helvetica Chimica Acta

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“…In cases where interfering chelation is not possible, yields of coupling reactions can approach quantitative. Thus stannyl enolethers provide an opening for a potentially wide range of pteridine 6‐ketones (34), (Scheme a) in the lumazine series. Related work in the naturally occurring 2‐amino‐4‐oxopteridine series, in which the pyrimidine is protected at both N3 and the 2‐amino group has been used in the syntheses of compounds related to the molybdenum cofactor (35).…”

Section: Diversity Through Metal‐mediated Coupling Reactionsmentioning

confidence: 99%

“…As several of these reactions illustrate, the potential of alkynes for further structural elaboration is high. As a further example, the hydration of pteridinyl alkynes has been described (34).…”

Section: Diversity Through Metal‐mediated Coupling Reactionsmentioning

confidence: 99%

The diversity‐oriented synthesis of pteridines—achievements and potential for development

Suckling¹

2013

IUBMB Life

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The importance of pteridines in the key cofactors, tetrahydrofolate and tetrahydrobiopterin, has encouraged the development of the chemistry and chemical biology of pteridines. In order to investigate the latter, versatile synthetic methods are required to prepare designed relatives of the natural cofactors for use as potential drugs or biological probes. Recently, diversity-oriented synthesis has become a particularly powerful and versatile approach to the synthesis of pteridines and related heterocyclic compounds. This article describes and discusses available methods using radical, electrophilic, nucleophilic, and organometal mediated substitution reactions.

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“…The systematic investigation of the marine world for the discovery of novel biologically active compounds emerged more recently, about thirty years ago [14]. In this context, bioluminescence is a fascinating phenomenon that flourishes predominantly in animals of deep ocean waters, and remains restricted to a few groups in terrestrial ecosystems [15][16]. Recently, we addressed the question of the origin and evolution of bioluminescence [17][18], i.e.…”

Section: Introductionmentioning

confidence: 99%

Discovery and Validation of a New Family of Antioxidants: The Aminopyrazine Derivatives

Dubuisson

Rees²,

Marchand‐Brynaert

2004

mrmc

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Coelenteramine (2-amino-1,4-pyrazine derivative), one of the metabolites of the oxidative degradation of coelenterazine (imidazolopyrazinone derivative), is endowed with excellent antioxidative properties towards ROS/RNS, like its mother-compound. This crucial discovery, made during the study of natural bioluminescent compounds (luciferins), has stimulated the development of synthetic aminopyrazine derivatives as new leads in medicinal chemistry in the field of antioxidant-based therapies. Synthetic approaches, theoretical evaluation, radical scavenging properties in acellular and cellular tests, and in vivo evaluation are described, and illustrated with representative aminopyrazines. Tested compounds were inhibitors of lipid peroxidation and good quenchers of peroxynitrite. They efficiently protect isolated LDL against radical-induced damages. They prevent cell constituents (membranes, DNA) against injuries by various oxidative stressors (UV irradiation, hydroperoxide treatment, oxidized LDL toxicity). Lastly, aminopyrazines are remarkably active in the "hamster cheek pouch" assay (in vivo protection against ischemia-reperfusion damages).

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Studies on pyrazines. Part 37. Synthesis of 6-propionylpteridine-2,4(1H,3H)-dione and its 1- and/or 3-methyl derivatives from marine natural products

Cited by 11 publications

References 18 publications

Pteridines. Part CXVII

Pteridines. Part CXVII

The diversity‐oriented synthesis of pteridines—achievements and potential for development

Discovery and Validation of a New Family of Antioxidants: The Aminopyrazine Derivatives

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