Synthesis of 6-alkenyl- and 6-alkynylpurines with cytokinin activity

Bråthe, Anders; Gundersen, Lise‐Lotte; Rise, Frode; Eriksen, Aud Berglen; Vollsnes, Ane V.; Wang, Linea

doi:10.1016/s0040-4020(98)01027-8

Cited by 62 publications

(24 citation statements)

References 47 publications

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“…To improve the yield, the reaction was further optimized. Similar result was obtained when Pd(dba) 2 was used instead of Pd(OAc) 2 4 as a base led to further improvement and the reaction under phosphane-free conditions gave 5a in 89 % yield. The combination of Na 3 PO 4 with diPheCy 2 P lowered the yield to 50 % (Table 1, Entries 6 and 7), but a high yield of the Heck product was obtained when Pd(OAc) 2 was used in combination with biPheCy 2 P and iPr 2 NEt (Table 1, Entry 8).…”

Section: Resultssupporting

confidence: 76%

“…Repetition of the reaction between 9-benzyl-6-iodopurine (1) and butyl acrylate under the previously described conditions [21] confirmed that in the presence of Pd(PPh 3 ) 2 -Cl 2 or Pd(PPh 3 ) 4 only decomposition of starting compounds takes place. However, when the reaction was performed under phosphane-free conditions the dimer 2 became the main product of the reaction, but accompanied by a small amount of the desired Heck reaction product 3 (Scheme 1).…”

Section: Resultssupporting

confidence: 69%

“…[1] 6-Alkenylpurines, for example, are associated with antimycobacterial, [2] cytotoxic [3] and cytokinin [4] activity and with inhibition of 15-lipoxygenase.…”

Section: Introductionmentioning

confidence: 99%

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Heck Reactions of 6‐ and 2‐Halopurines

Tobrman

Dvořák

2008

Eur J Org Chem

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Under the conditions of the Heck reaction, 9-benzyl-6-iodopurine affords mainly the corresponding 6,6Ј-dimer, the Heck product being formed only in low yield (Յ12 %). With 7-benzyl-6-iodopurine the dimerization is suppressed and the Heck product is obtained in 32-91 % yield. 9-Substituted 6-chloro-2-iodopurines react smoothly, giving 2-alkenyl-6- IntroductionAmong a vast number of biologically active purine derivatives, alkenylpurines play an important role.[1] 6-Alkenylpurines, for example, are associated with antimycobacterial, [2] cytotoxic [3] and cytokinin [4] activity and with inhibition of 15-lipoxygenase.[5] Some 6-alkenylpurines have been designed as covalent analogues of DNA base pairs [6] or novel cross-linking agents, [7] and have also been used for the synthesis of fluorescent nucleoside analogues.[8] Moreover, 2-alkenyladenosine derivatives have been reported to function as inhibitors of adenosine receptors. [9] Several methodologies have been used for the preparation of alkenylpurines. 6-Styrylpurine was first prepared by condensation of 6-methylpurine with benzaldehyde in the presence of HCl.[10] Another, more general, synthetic approach to 6-alkenylpurines, is based on Wittig reactions between 9-protected (purin-6-yl)methylene-triphenyl-λ 5 -phosphanes (Wittig reagents) and aldehydes or ketones.[11]Cyclic 6-alkenyloxypurines have been prepared by intramolecular cyclization of 6-(hydroxyalkyn-1-yl)purines, [12] while 6-enaminopurines are accessible by addition of amines to 6-alkynylpurines.[13] Partial hydrogenation of 2-alkynyl- [14] and 8-alkynylpurines [15] to give the corresponding alkenes has also been reported. Hydrogenation of 6-alkynylpurines to 6-alkenylpurines was reported to proceed satisfactorily only with 9-unprotected bases, with overhydrogenation taking place otherwise.[4a] However, the most versatile methodology for the preparation of alkenylpurines -nowadays used almost without exception -is based on transitionmetal-catalyzed cross-coupling reactions.[16] Alkenylpurines [a]

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Section: Resultssupporting

confidence: 76%

Section: Resultssupporting

confidence: 69%

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Heck Reactions of 6‐ and 2‐Halopurines

Tobrman

Dvořák

2008

Eur J Org Chem

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“…All measurements of 15-lipoxygenase activities were carried out in a Shimadzu UV-160A spectrophotometer (Shimadzu, Kyoto, Japan) at 20Ϫ22°C. Compounds available by literature methods: 1a and 1b [15], 1c, 7c and 8c [16], 2 and 7n [17], 4a and 4b [3], 7a, 7b, 8a and 8b [1], 7h [4], 7k [18], 7l, 7m and 9a [19].…”

Section: Acknowledgmentsmentioning

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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“…In this context, Heck arylation and reductive Heck alkylation at the C-6 position of purines have been accomplished. [5,6] However, reactions of purine nucleosides in general, and specifically those at the C-8 position, are unknown. Modification at C-8 could have important biological consequences.…”

Section: Introductionmentioning

confidence: 99%