Cyclopentylamine derivative

Various 2 -C -alkylated derivatives of carbocyclic 5-methyluridine have been prepared, as have 6 -alkoxy and -acyloxy-derivatives of carbocyclic thymidine (119), in order to test the effect of the structural alterations on DNA/RNA duplex stability. A short and high-yielding synthesis of carbocyclic bromo-vinyl-deoxyuridine (BVDU) has been described, involving a cyclopentylamine derivative as an intermediate. Carbocyclic BVDU and carbocyclic 2 -deoxy-guanosine have been made by a modification of an earlier route to carbocyclic 2 -deoxynucleosides, involving a microbiological reduction. Racemic difluoro-carbocyclic nucleosides of type 120 have been made via the fluorination of ( )-JV-Boc-2-azabicyclo[2.2.1]hept-5-en-3-one (see Vol.28, p.284), and the (+)-enan-tiomer of 2-azabicyclo[2.2.1]hept-5-en-3-one has been converted into the (—)-enomtiomer, which is of considerable use in the synthesis of carbocyclic nucleosides in the o-series. ... 

Insertion of isocyanides into zirconacyclopentanes and zirconacyclopentenes affords the corresponding zirconocene q -imine complexes. Cyclopentylamine derivatives could be prepared by trapping of the insertion intermediates using alkenes, alkynes, and carbonyl compounds [50]. For example, insertion of phenylisocyanide into bicyclic zirconacyclopentenes affords iminoacyl complexes that rearrange to give a, )0-unsaturated zirconocene q -imine complexes. These complexes react with alkenes or alkynes to give cyclopententylamines (Eq.48) [51]. 

This chemistry was extended to a number of bicyclic alkenes and dienes utilizing various chelating axially chiral bisphosphine iridium catalysts (Scheme 11.5) [29]. Further synthetic transformations of the chiral hydroamination product 13 provide access to functionally substituted chiral cyclopentylamines with multiple stereocenters, such as 14 and IS. It should be noted that alkylamines, such as octylamine or N methyl aniline, and sterically encumbered aniline derivatives, such as 0 toluidine or o anisidine did not undergo hydroamination reactions under these conditions. 

The syntheses of carbocyclic analogs of phosphononucleosides (29) and (30a-c) have been reported. Phosphonic acid (29) was obtained by introduction of the benzoylated thymine on the 2(4-hydroxycyclopent-2-enyl)ethyl phosphonic acid diisopropyl ester under Mitsunobu conditions while (30a-c) were prepared by building-up the base around a phosphono-cyclopentylamine moi-ety. The vinylphosphonate derivatives of uridine, cytidine and cytosine ara-binoside (31a-c) have been prepared by Wittig condensation of [(diethoxyphos-phinyl)methylidene]triphenylphosphorane with the appropriately protected 5-aldehydic nucleoside derivatives. Dihydroxylation of the novel vinyl phosphon-ates offered the dihydroxylated phosphonate derivatives (32a-c). Each of these novel compounds was evaluated as substrates for the enzyme nucleotide monophosphate kinase, and their toxicity to K562 cells. All analogues were found to be poorly phosphorylated by the kinase and exhibited poor in vivo toxicity. ... 

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