Synthesis of cyclopentenyl carbanucleosides via palladium(0) catalysed reactions

Kapeller, H.; Marschner, Christoph; Weissenbacher, M.; Grieng, H.

doi:10.1016/s0040-4020(97)10380-5

Cited by 13 publications

(4 citation statements)

References 36 publications

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“…The direct introduction of cytosine and guanine failed. However, the N 4 ‐benzoyl derivative of cytosine44 afforded 10 e in up to 84 % yield. For the introduction of guanine, the N 2 ‐acetyl‐ O ‐diphenylcarbamoyl derivative was employed according to the method of Robins and co‐workers45 to give 10 f as a single regioisomer in 76 % yield.…”

Section: Resultsmentioning

confidence: 99%

“…However, the formation of Ph 3 PO (as a result of Ph 3 P oxidation during workup) caused severe separation problems and isolated products 10 were often contaminated with significant amounts of Ph 3 PO 47. Therefore, a different catalyst system consisting of [Pd(dba) 2 ] (2 mol %) and ( i PrO) 3 P (14 mol %) was applied (Method B) 44. While the yields were comparable to those obtained with [Pd(PPh 3 ) 4 ], chromatographic product purification was generally easier.…”

Section: Resultsmentioning

confidence: 99%

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Transition‐Metal‐Mediated Synthesis of Novel Carbocyclic Nucleoside Analogues with Antitumoral Activity

Velcicky

Lanver

Lex

et al. 2004

Chemistry A European J

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A diversity-oriented, enantioselective synthesis of new (monoprotected) carbocyclic nucleoside analogues (CNAs) with the nucleobase attached to a 3-hydroxymethyl-4-trialkylsilyloxymethylcyclopent-2-en-1-yl scaffold was developed. As a key intermediate, racemic (5SR,8RS)-8-allyloxy-2-trimethylsilyl-7-oxa-bicyclo[3.3.0]-oct-1-en-3-one was prepared from 1,1-diallyloxy-3-trimethylsilyl-2-propyne in a cobalt-mediated Pauson-Khand reaction. The enantiomerically pure material was obtained through efficient kinetic resolution (selectivity factor s >/= 40 at -78 degrees C) by means of an oxazaborolidine-catalyzed borane reduction (CBS reduction) with catecholborane. The absolute configuration of the resolved products was determined by CD spectroscopy, Mosher ester analysis, and chemical correlation. Subsequent steps involve diastereoselective ketone reduction and fully regio- and diastereoselective introduction of the nucleobase through Pd(0)-catalyzed allylic substitution. The generality of the method was demonstrated by preparation of CNAs in both enantiomeric series with all five natural nucleobases, as well as 5-bromouracil, 5-fluorouracil, and 6-chloropurine. Screening of the various compounds in a cytotoxicity assay with BJAB and ALL tumor cell lines revealed that some of the compounds possess pronounced antitumoral properties (LD50 values down to 9 microM, as determined by lactate dehydrogenase release after 48 h). By measuring DNA fragmentation, it could be shown that the activity results from induction of apoptosis.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Transition‐Metal‐Mediated Synthesis of Novel Carbocyclic Nucleoside Analogues with Antitumoral Activity

Velcicky

Lanver

Lex

et al. 2004

Chemistry A European J

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show abstract

“…Acetate and carbonate derivatives were found to be most useful for the palladium-catalyzed substitution at the allylic position with nucleoside bases. A basic catalyst, such as NaH, LiH and n -BuLi, Cs 2 CO 3 , or even Et 3 Al, was necessary when the acetate derivatives were used . Long reaction times in polar and high-boiling solvents are usually necessary because of the poor solubility of the salts of the heterocycles in the reaction media.…”

Section: Palladium-mediated Allylic Alkylation To Nucleoside Analoguesmentioning

confidence: 99%

“…A basic catalyst, such as NaH, LiH and n-BuLi, Cs 2 CO 3 , or even Et 3 Al, was necessary when the acetate derivatives were used. 166 Long reaction times in polar and high-boiling solvents are usually necessary because of the poor solubility of the salts of the heterocycles in the reaction media. However, methyl carbonate derivatives can be condensed under Pd(0) catalysis with nucleobases under neutral reaction conditions.…”

Section: Palladium-mediated Allylic Alkylation To Nucleoside Analoguesmentioning

confidence: 99%