Synthesis of 6-substituted purin-2-ones with potential cytokinin activity

Andresen, Geir; Eriksen, Aud Berglen; Dalhus, Bjørn; Gundersen, Lise‐Lotte; Rise, Frode

doi:10.1039/b101327k

Cited by 18 publications

(11 citation statements)

References 29 publications

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“…The exception to this generalization is the unusually potent Complex I inhibition by 58, 73, and 75 where the piericidin A1 side chain (but not farnesyl) appears to compensate for their removal (Figure 4). Significantly, the series of analogues bearing the farnesyl side chain exhibit trends consistent with expectations of a simple coenzyme Q mimic where both the C4' hydroxyl group and the C5' methyl group each increase either the Complex I inhibition or L1210 cytotoxicity approximately 30-100 fold with the former target-based assay (Complex I) assay exhibiting IC 50 's approximately 10-fold lower than the cell-based (L1210) assay. In marked contrast, the series bearing the piericidin A1 side chain exhibited much smaller 1-2.5 fold losses in Complex I activity with removal of either the C4' hydroxyl or C5' methyl group, while experiencing even greater 200-500 losses in cytotoxic activity in the cellular assay.…”

Section: Compound Assessmentssupporting

confidence: 61%

Total Synthesis of Piericidin A1 and B1 and Key Analogues

et al. 2006

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Full details of the total synthesis of piericidin A1 and B1 and its extension to the preparation of a series of key analogues are described including ent-piericidin A1 (ent-1), 4'-deshydroxypiericidin A1 (58), 5'-desmethylpiericidin A1 (73), 4'-deshydroxy-5'-desmethylpiericidin A1 (75), and the corresponding analogues 51, 59, 76, and 77 bearing a simplified farnesyl side chain. The evaluation of these key analogues, along with those derived from their further functionalizations, permitted a scan of the key structural features providing new insights into the role of the substituents found in both the pyridyl core as well as the side chain. A strategic late stage heterobenzylic Stille crosscoupling reaction of the pyridyl core with the fully elaborated side chain permitted ready access to the analogues in which each half of the molecule could be systematically and divergently modified. The pyridyl cores were assembled enlisting inverse electron demand Diels-Alder reactions of Nsulfonyl-1-azabutadienes while key elements of side chain syntheses include an anti selective asymmetric aldol to install the C9 and C10 relative and absolute stereochemistry (for natural and ent-1) and a modified Julia olefination for formation of the C5-C6 trans double bond with convergent assemblage of the side chains.

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Section: Compound Assessmentssupporting

confidence: 61%

Total Synthesis of Piericidin A1 and B1 and Key Analogues

et al. 2006

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“…Product 86 was obtained in 48% yield by exposing the monomer as an oil to daylight irradiation. 190 Dimerization of styryl-substituted 2,3-dicyanopyrazines led to products like 87 , which are of interest in the context of new fluorescent materials. 191 In all cases shown in Figure 5 , the photodimerization occurred vertically (i.e., with a preference for the HT dimer in the trans-syn-trans configuration).…”

Section: Direct Excitation and Sensitizationmentioning

confidence: 99%

Recent Advances in the Synthesis of Cyclobutanes by Olefin [2 + 2] Photocycloaddition Reactions

et al. 2016

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The [2 + 2] photocycloaddition is undisputedly the most important and most frequently used photochemical reaction. In this review, it is attempted to cover all recent aspects of [2 + 2] photocycloaddition chemistry with an emphasis on synthetically relevant, regio-, and stereoselective reactions. The review aims to comprehensively discuss relevant work, which was done in the field in the last 20 years (i.e., from 1995 to 2015). Organization of the data follows a subdivision according to mechanism and substrate classes. Cu(I) and PET (photoinduced electron transfer) catalysis are treated separately in sections 2 and 4, whereas the vast majority of photocycloaddition reactions which occur by direct excitation or sensitization are divided within section 3 into individual subsections according to the photochemically excited olefin.

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“…The aqueous phase was extracted with EtOAc (2 ϫ 40 mL). The combined EtOAc extracts were dried (MgSO 4 ) and evaporated under reduced pressure, and the crude product was purified by flash chromatography on silica gel eluting with hexane-EtOAc (95:5) followed by hexaneEtOAc-CH 2 …”

Section: -Phenylmethyl-9-(tetrahydro-2h-pyran-2-yl)-9h-purine 3amentioning

confidence: 99%

6‐Substituted Purines as Inhibitors of 15‐Lipoxygenase; a Structure‐Activity Study

Bråthe

Gundersen

Malterud

et al. 2005

Archiv der Pharmazie

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15-lipoxygenase (15-LO) has been implicated in oxidation of low-density lipoproteins (LDL), a process believed to be important for the development of atherosclerosis, as well as other pathogenic conditions. Potent and selective inhibitors of 15-LO may have a drug potential. In this study, purines with a variety of substituents have been examined as inhibitors of 15-lipoxygenase (15-LO) from soybeans. Several 6-substitued purines where the purine ring and a phenyl ring in the substituent were separated by a "spacer" were synthesized and their ability to inhibit the enzyme was explored. Sepa ration of the purine and the phenyl rings with none, one or two sp3-carbons resulted in essentially inactive compounds, trans-styrylpurines and phenylethynylpurines, on the other hand, they exhibited activity close to the well-known 15-LO inhibitor quercetin. High activity was also found when the "spacer" was a trans-cyclopropyl ring. The shape of the spacer was important; a corresponding cis-cyclopropylpurine exhibited much less affinity for the enzyme. Only minor differences in inhibitory activity against 15-LO were found regardless of whether an N-substituent was situated on N-9 or N-7, even when the N-substituent was relatively large. Also, a variety of substituents in the purine 2- and 8-position were well tolerated.

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Synthesis of 6-substituted purin-2-ones with potential cytokinin activity

Cited by 18 publications

References 29 publications

Total Synthesis of Piericidin A1 and B1 and Key Analogues

Total Synthesis of Piericidin A1 and B1 and Key Analogues

Recent Advances in the Synthesis of Cyclobutanes by Olefin [2 + 2] Photocycloaddition Reactions

6‐Substituted Purines as Inhibitors of 15‐Lipoxygenase; a Structure‐Activity Study

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Synthesis of 6-substituted purin-2-ones with potential cytokinin activity

Cited by 18 publications

References 29 publications

Total Synthesis of Piericidin A1 and B1 and Key Analogues

Total Synthesis of Piericidin A1 and B1 and Key Analogues

Recent Advances in the Synthesis of Cyclobutanes by Olefin [2 + 2] Photocycloaddition Reactions

6‐Substituted Purines as Inhibitors of 15‐Lipoxygenase; a Structure‐Activity Study

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Recent Advances in the Synthesis of Cyclobutanes by Olefin [2 + 2] Photocycloaddition Reactions