Synthesis of -aristeromycin

Kitagawa and coworkers have used this strategy for the preparation of pseudo-nucleosides exhibiting various biological activities. The synthesis of (-)-aristeromycin from D-glucose is demonstrated in Scheme 7.17.90... 

The rather low reactivity of the 3-p-tolylsulfinyl acrylates (they do not react with furan even under forcing conditions) prompted the search for more reactive dienophiles. In this context, pyridylsulfinyl derivatives proved to be more efficient than the arylsulfinyl ones. Thus, menthyl-3-(2-pyridylsulfinyl)propenoates 14a and 14b were prepared from (+)-menthyl propiolate in low yields [34]. Their reactions with cyclopentadiene proceed smoothly in the presence of Et2AlCl at -70°C to afford just one endo diastereoisomer 15a or 15b [35] (in the absence of the catalyst the 7r-facial selectivity for the endo approach was lower than that observed for the p-tolylsulfmyl derivatives [10c]). These compounds were transformed into 16a or 16b [36] respectively (Scheme 8), both allowing the synthesis of the bicyclic lactone 17 (known as Ohno s lactone), a key intermediate in Ohno s synthesis of (-)-aristeromycin and (-)-neplanocin A [37]. 

Boyer, S.J. et al. Carbocyclic Nucleoside Analogs. I. Concise Enantioselec-tive Synthesis of Functionalized Cyclopentanes and Formal Total Synthesis of Aristeromycin. 2.4 1997 [109]... 

Trost and his group have used both of these palladium-catalysed alkylations in a synthesis of aristeromycin from epoxycycl ope nta diene. The cis stereochemistry of this carbocyclic nucleotide analogue is of paramount importance and was completely controlled by retention of configuration in both substitutions. 

One of the best examples of an enzymatic dephosphorylation for a synthetic purpose is shown in the entry 5 ofTable 13-6. A 5 -ribonucleotide phosphohydrolase was used in the synthesis of (-)-aristeromycin, a carbocyclic analog of adenosine. The (-)-enantiomer of aristeromycin shows some cytostatic and antiviral activity, while the (+)-enantiomer is inactive. The racemate ( )-5 -phosphorylated aristeromycin was resolved by selective hydrolysis of the (-)-enantiomer with the hydrolase. The (-)-alcohol and the (+)-5 -phosphate derivative were separated easily on a silica gel column. Hydrolysis of the (-t-)-enantiomer with calf intestinal phosphatase yielded pure (+)-alcohol. 

A synthesis of aristeromycin" makes use of the displacement of a pyrimidine 4-chloride to allow introduction of the amine and the generation of the 4,5-diaminopyrimidine for subsequent closure of the five-membered ring. 

Koizumi and coworkers have developed a new enantiomerically pure a,p-unsaturated sulfoxide dienophile bearing the isoborneol group as a chiral auxiliary, dimethyl (f )-2-(10-isoborneolsulfinyl)maleate (214), which has been successfully employed as a chiral synthetic equivalent of dimethyl acetylenedicarboxylate [174], The dienophile (214) underwent cycloaddition with cyclopentadiene, in the presence of zinc chloride, with high stereo- and diastereoselectivity (92% single endo diastereoisomer, 6% single exo diastereoisomer) to yield the major cycloadduct (215), which was subsequently transformed into the half-ester (216), an intermediate in the syntheses of (-)-aristeromycin (199) and (-)-neplanocin A (200). Cycloadduct (215) has also recently been used for the synthesis of bicyclo[2.2.1]heptane lactone (217) [175,177], which itself is an intermediate in the synthesis of the iridoid (-)-boschnialactone [176] (218) (Scheme 5.69), and also in the formal synthesis of (-)-aristeromycin (199) and (-)-neplanocin (200) [177]. 

There has been a further report on the synthesis of aristeromycin... 

Exalt AM, Jones MF, Mo CL, Myers PL, Paternoster IL, Singh H, Storer R, Weingarten GG, Williamson C, Biodie AC, Cook ], Lake DE, Meerholz CA, Turnbull P, Highcock RM. Synthesis of (-)-aristeromycin and X-ray structure of (-)-carbovir. J Chem Soc Perkin Trans (I) 199h 2467-2477. 

Tanake et al. [253] demonstrated the enzymatic synthesis of the sugar moiety of carbocyclic nucleosides required for the total synthesis of (-)-aristeromycin 150. Using lipase from Rhizopus delamar the enantioselective hydrolysis of mei o-l.S-bis(acetoxymethyl)-2-traw5 -alkylcyclopentane (151,152) was carried out to prepare the chiral monoacetate (153,154) in more than 96% e.e. (Fig. 53). The chiral monoacetate was also used in the synthesis of optically active 11-deoxyprostaglandins [254]. 

---