Nucleosides precursor, carbocyclic

Maycock, C D. et al. An Application of Quinic Acid to the Synthesis of Cyclic Homochiral Molecules A Common Route to Some Interesting Carbocyclic Nucleoside Precursor. 2.4 1993 [151]... 

SCHEME 10.41 Preparation of a carbocyclic nucleoside precursor via a sugar-directed hetero Diels-Alder reaction. 

Katagiri, N., Yamamoto, M., and Kaneko, C., 3-Acetoxy-2-dimethylphosphonoacrylates. New dienophiles and their use for the synthesis of carbocyclic C-nucleoside precursors by the aid of RRA reaction, Chem. Lett., 1855, 1990. 

The Diels-Alder reaction of these chiral dioxinones with cyclopentadiene has provided a highly stereoselective route to carbocyclic C-nucleoside precursors (27) (Scheme 11) <89CPB2615>. The [2 + 2] cycloaddition of the same menthone-derived dioxinone with cyclopentene has also been observed <87CPB3539>. 

Carbocyclic nucleoside precursor 154 was synthesized in 36% overall yield from an iV-hydroxy-D-alanine derivative by a reaction pathway involving oxidation, hetero-Diels-Alder cycloadditon of the nitroso intermediate to cyclopen-tadiene to give a chiral 1,2-oxazine, syn-dihydroxylation, and reductive cleavage. 

The carbocyclic analogue of puromycin has been prepared from the racemic carbocyclic nucleoside precursor, resolving the diastereo-isomers formed after acylation by p-methoxyphenylalanine the D-form... 

The carbocyclic nucleoside precursors 86 have been prepared from a known hydroxycyclopentanedicarboxylic ester (see H.-J. Gais et. ai, J. Org. Chem., 1989,54, 5115). ... 

A short synthesis of the carbocyclic analogue of S-phosphoribosyl-1-pyrophosphate from the known (C.R. Johnson et al.. Tetrahedron, 1984, 40, 1225) chiral ketone 72 has been described. Syntheses of carba-a-D-arabinofuranose and of the carba-nucleosides (+)-cyclaradine and (+)- caH>a>P-D-arabinofuranosyluraciI from key intermediate nitro-compound 73 have been reported. A short synthesis of Ohno s lactone, 74 in 54% overall yield from (+)-(lR)-e/u/o-5-norbomene-2-carboxylic acid, as a useful carbocyclic nucleoside precursor, has been reported." See Chapter 20 for the synthesis of carbocyclic tiazofurin and other carbocyclic nucleosides. 

Further work on griseolic acid analogues has been reported (see Vol. 25, p. 232), giving guanosine analogues, e.g. 28, instead of adenine derivatives and its 3, 4 -stereoisomers together with carbocyclic analogues. Other carbocyclic nucleoside derivatives of aristeromycin and a synthesis of carbovir are mentioned in Chapter 20, and a synthesis of the carbocyclic nucleoside precursor, Ohno s lactone, is referred to in Cluster 18. 

Deoxy-5 -fluoroadenosine (911) and the analogs 910, 912, 913 were prepared by coupling of 5-deoxy-5-fluoro-D-ribofuranose and 6-chloro-purine. 2, 5 -Dideoxy-5 -fluoroadenosine (914) was prepared through a displacement reaction of the corresponding 5 -0-tosyl precursor with fluoride (BU4NF in DMF). The carbocyclic nucleosides 915 and 916 have been prepared and their antiviral activities evaluated. 

The carbocyclic 434, precursor of nucleoside analogues, was synthesized from the commercially available (—)-/3-pinene 433. The Beckmann rearrangement was used to cleave the carbocyclic ring and cis stereochemistry of the ring substituents is guaranteed (equation 183). 

Campbell, J.A. et al. Chirospecific Syntheses of Precursors of Cyclopentane and Cyclopentene Carbocyclic Nucleosides by [3+3]-Coupling and Transannular Alkylation. 2.4 1995(111]... 

Gallos, J.K. et al. Facile Synthesis of Enantiomerically Pure Carbafuranoses Precursors of Carbocyclic Nucleosides. 2.1 2001 [120]... 

Park, K.H. et al. Enantioselective Synthesis of (IR,4S)-I-Amino-4-(hydroxy-methyl)-2-cyclopentene, a Precursor for Carbocyclic Nucleoside Synthesis. 2.4 1994 [165]... 

R,4S)-(+)-4-Hydroxy-2-cyclopentenyl acetate [(+)-1] is an important synthetic precursor. It provides optically active starting material via the versatile intermediate 4-oxo-2-cyclopentenyl acetate,7 for important cyclopentanoids such as the prostaglandins8 and carbocyclic nucleosides.9 Because of the medicinal significance of these compounds more efficient routes, with better enantioselectivities have been devised to nonracemic 1. Enzymatic catalysis has become the dominant methodology for induction of this optical activity. 

Compared with the reaction with cyclohexadiene, the diastereoselectivity of the Diels-Alder reaction of 122 with cyclopentadiene was found to be lower under a variety of reaction conditions. In the latter case, the cycloaddition afforded the [2.2.1] bicyclic salt 129, which was further converted to 130 — the precursor of a carbocyclic L-nucleoside [95] (Scheme 10.41). 

Some carbocyclic nucleoside phosphonates have been described. There has been a further report on compounds of type 208 (see Vol. 28, p. 291), with both purine and pyrimidine bases. Although initially made as racemates, a precursor diol could be resolved by enantioselective acetylation using a lipase and vinyl acetate.The triphosphate analogues 209 (B=Gua, Ade) have been made from the previously-described monophosphonates (Vol. 29, p. 285), and the cyclopropyl-fused diphosphate analogues 210 (X=CH2 and O) were also reported, along with their enantiomers. Trani-compounds of type 211 (n=l-3) have been made as racemates,and so have the related cw-isomers (n=l or 2). ... 

The enantiomer of 154 can be made by using the corresponding L-alanine derivative as the chiral auxiliary. Compound 154 is also a precursor to the antiviral carbocyclic nucleoside, neplanodn A, and the antitumour agent, 5 -noraristeromycin. ... 

A review has discussed selective biocatalytic modifications of conventional nucleosides, carbocyclic nucleosides and C-nucleosides, including such topics as selective acylation of nucleosides, regioselective deacylation, and enzymic resolution of precursors of carbocyclic and C-nucleosides. The enzymatic synthesis of antiviral nucleosides has also been reviewed, in Chinese. A survey has been given of synthetic approaches to nucleosides in the unnatural L-series, and their potential use as antiviral and anticancer agents. ... 

Carvone was used as a precursor for the synthesis of the cyclohexene 159, and this was used to make the cyclohexenyl nucleoside analogue 160. The same chiral precursor was also manipulated to give the enantiomers of 159 and 160. Both enantiomers of 160 showed potent antiherpetic activity. Molecular modelling of the binding of both compounds to the active site of HSV-1 thymidine kinase was carried out, and a model for the binding of both enantiomers was proposed.An analogue of carbocyclic 2 -deoxyuridine, conforma-tionally-restricted due to a 6,6 -oxido-link (Vol. 32, p. 278), has now been reported in optically-active form, in the L-series. ... 

Treatment of the epoxide 98 with TMSCN led unexpectedly to compound 99. Epoxidation of cyclopentadiene yields a di-epoxide which on treatment with sodium azide gives a mixture of products from which cyclitol 100 can be obtained as a useful precursor to carbocyclic nucleosides and amino cyclitols. 

The preparation of the carbanucleoside aristeromycin and carbacyclic precursors of neplanocin A are mentioned in Chapter 19. The preparation of intermediates for the synthesis of unsaturated carbocyclic nucleosides is covered in Chapter 20. 

A review on natural product synthesis using asymmetric Diels-Alder reactions includes references relevant to the synthesis of carbocyclic nucleosides in an enantiomerically pure state.i52 The phosphonate (103), made via Diels-Alder reaction, gives rise to (104), claimed as a potential precursor for carbocyclic C-nucleosides, on treatment with K2C03-NaBH4-i53... 

Work on the synthesis of 2, 3 -didehydro-2, 3 -dideoxy carbocyclic nucleosides has led to the emergence of the guanosine analogue carbovir (105, B=Gua) as a potent and selective anti-HIV agent. 154 The precursor (106) of the bioactive (-)-isomer of carbovir can be resolved by the enantioselective hydrolysis of the unwanted isomer by a Pseudomonas... 

The reaction of 2,5-anhydro-3,4-0-isopropyIidene-DL-allose (450) (see Vol. 9, p. 22) with ethyl triphenylphosphoranylidene pyruvate at 90 °C gave the internal Michael-addition product (451) via the a)S-unsaturated ketoester formed in the Wittig reaction. Homo-C-nucleosides (452) containing 6-azauracil or 4-hydroxy-5-carboxamidopyrazole were elaborated from (451). Details of an earlier synthesis of the racemic hemiacetal (454), a precursor of carbocyclic C-nucleosides, have been published, together with an improved synthesis of (454) via the lactone (453) part of this route is outlined in Scheme 87. Condensation of the lactone... 

The previously described 7-deazapurine carbocyclic nucleoside synthesis (see Scheme 1) indicated that the most efficient route to 22 would be via reaction of the protected chiral amine 23 with the dimethylacetal of 2-(2-amino-4,6-dichloropyrimidin-S yl)acetaldehyde followed by ring closure, hydrolysis and dqirotection. A review of the literature revealed two enantioselective routes to cyclobutyl derivatives that had been used in the chiral synthesis of carbocyclic oxetanocins and could be employed for preparing a precursor to 23. In one case, however, the initial step involved a [2-i-2]-cycloaddition reaction of not easily obtainable reagents in the presence of a chiral titanium compound as... 

The preparation, as a precursor for carbocyclic nucleosides, of dte simple aminopmitane derivative 61 from S-aspartic acid and the isolation from a sponge of six cyclopentane glycolipids such as 62 which display insect antifeedent activity on a fisb species have been described. 

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