Synthesis of Optically Active 6‐Alkynyl‐ and 6‐Alkylpurines as Cytokinin Analogs and Inhibitors of 15‐Lipoxygenase; Studies of Intramolecular Cyclization of 6‐(Hydroxyalkyn‐1‐yl)purines

Abstract

Optically active 6‐alkynyl‐ and 6‐alkylpurines have been synthesized. These compounds can be regarded as analogs of cytokinin plant growth hormones. The analogs were examined as growth stimulators and as inhibitors of 15‐lipoxygenase (15‐LO). The (S)‐enantiomer of 6‐(5‐hydroxy‐4‐methylpent‐1‐yl)purine exhibited profound growth stimulation activity, especially at low concentrations. 6‐(Hydroxyalkyn‐1‐yl)purines were found to cyclize by nucleophilic exo attack from the hydroxy group at the triple bond. (Z)‐Isomers were formed under acidic conditions. Plant growth stimulators and 15‐LO inhibitors were identified among the cyclization products. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

Intramolecular Hydroalkoxylation and Hydroamination of Alkynes Catalyzed by Cu(I) Complexes Supported by N-Heterocyclic Carbene Ligands

“…87 Similarly, Gundersen's group observed Z-to-E isomerization with a bulkier purine group with a ΔG ‡ of 28 kcal/mol. 88 These data suggest that a Z-to-E isomerization with the Cu-based catalyst may be feasible under the reaction conditions and must be considered as a mechanistic pathway. However, in the present case, calculations indicate that isomerization of the trans insertion product to the cis must overcome a barrier of 32.1 kcal/mol.…”

Transition metals in organic synthesis: Highlights for the year 2005

“…(14) Heterocyclic ring systems were shown to readily participate in Sonogashira-type couplings [175,306]. Some more complex examples include reaction of 5-iodoarabinosyluridine [307], 3-iodofuran [308], 6-chloro-9H-purine [309], 8-bromoadenosine [310], 2,6-bis(4-iodopyrazol-1-yl)pyridine [311], 6-chloro-3H-pyrimidin-4-one [312], bromo-oxabicyclo[3.2.1]octadienes [28], a triazolopyrazinyl bromide [172], 5-trifloxyindoles [29], 5-bromobenzofuran [183], 3-iodo-5-bromoindole and 3-iodo-5-bromo-3-indazole [182], 7-bromo-pyrido [2,3-b]pyrazine [185], 5-iodo-1,2,3-triazoles [186,313], 4,5-diiodoimidazole [314] and 4-iodo-2-bromoquinoline [315] derivatives. Sonogashira coupling of 2-iodophenols followed by cyclization to give benzofurans was reported [183].…”

Synthesis and anticancer activity of multisubstituted purines and xanthines with one or two propynylthio and aminobutynylthio groups

“…6-Alkynylpurines also show profound inhibitory activity against human 15-lipoxygenase. The inhibitors of these enzymes have been implicated in the oxidation of low density lipoproteins, and could have potential as drugs against artherosclerosis and other major diseases, such as for instance cancer, Parkinson’s, Altzheimer’s disease, heart infraction, and rheumatoid arthritis, which are also linked to free radicals (Brathe et al 2002 ; Berg et al 2005 ). 6-Alkynylpurines as cytokine analogs also possess a profound plant growth stimulation effect (Brathe et al 2003 ).…”