The first examples of reactions of Fischer carbene complexes with triynes are reported. The regioselectivity of the reaction of the two different alkyne functions in the symmetrical triyne depends on the nature of the substituent of the triyne. Bis-silyl-substituted triynes react at the central alkyne unit, whereas bis-aryl- and bis-alkyl-substituted triynes react at the end alkyne unit. The reaction of a Fischer carbene complex with a phenyl substituent also reacts with a bis-silyl-substituted triyne at the central alkyne unit but gives a furan product rather than the normal phenol product. It was also demonstrated that all three of the alkyne units in conjugated triynes could react in turn with a Fischer carbene complex to give access to trisquinones.

[reaction: see text] Enzymatic resolution of Boc-protected 4-aminocyclopenten-1-ol 4c gave both enantiomers 5c and 6c in high ee. Boc removal and separate condensation with chloropyrazolopyrimidine 18 provided elaborated 1,4-aminocyclopentenol derivatives 20 and 26, respectively. Separate treatment of 20 and 26 with Pd(0) under basic conditions induced cyclization to unsaturated polycycles 22 and 27, which, upon catalytic hydrogenation, were transformed to new cyclopentane-containing pyrazolopyrimidines 24 and 28, analogues of recently described novel phosphodiesterase inhibitors.

Carbocyclic nucleosides are of considerable interest for the development of new therapeutic agents. A key reaction in the preparation of many such nucleoside analogs is dihydroxylation of appropriately substituted cyclopentenes. While often considered a routine reaction, in this paper we report the dramatic influence of substituents on the facial selectivity of dihydroxylations. The substituted cyclopentene substrates are derived from acylnitroso cycloaddition reactions of cyclopentadiene, followed by N-O reduction and efficient enzymatic resolution. The results are directly utilized in a very efficient asymmetric synthesis of an antiviral carbocyclic nucleoside, noraristeromycin 5. Extensions towards synthesis of carbocyclic sinefungin 7 document the importance of realizing the substituent dependence of the dihydroxylation reaction.Infectious diseases are posing increasingly severe health risks, as evidenced by the recent SARS flu epidemic and the rapid spread of AIDS in developing countries. Accordingly, extensive research has been directed at finding effective therapeutic agents for the treatment of viral (eq 1)The natural carbocyclic nucleosides, neplanocin A 3 and aristeromycin 4 have potent antiviral activities ( Figure 1). 3 Aristeromycin (-)-4 is a carbocyclic analog of adenosine that terminates viral growth by inhibiting S-adenosyl-L-homocysteine (AdoHcy) hydrolase. 4 However, the high cytotoxicity of aristeromycin, presumably caused by the metabolism of 4 to its 5'-phosphates, has greatly hindered its therapeutic application. 5 In the search for a less toxic analog of aristeromycin, Schneller and coworkers found that the 5'-nor compound (±)-5 had improved antiviral activity with no cytotoxicity. 6 Subsequently, the same workers found the (-)-enantiomer of 5 was more active than the (+)-enantiomer. 7 Sinefungin 6 is a natural nucleoside first isolated from Streptomyces griseolus in 1973 and S. incarnatus in 1976. 8 Since its isolation from natural sources, sinefungin has been synthesized by several groups. 9 Preliminary bioassays showed that it inhibited the growth of several fungi 8 and viruses 10 , and that it showed significant antiparasitic 11 activity in vitro. There are two key features of the biological activity profile of sinefungin that stand out, one of which is its antiviral activity due to inhibition of methyltransferase. 12 Chemotaxis, neurosecretions, membrane receptor interactions, DNA modification-restriction, gene expression and cellular differentiation are among the diverse processes that methylation of biomolecules affects. 13 Sinefungin and derivatives have been tested against both vaccinia-and Newcastle disease virus-(guanine-7) methyltransferases. 10 The elucidation of structure-activity-relationships for sinefungin and its derivatives was attempted with these studies. Several features were found to be necessary in order to retain methyltransferase inhibition: (1) the L configuration of the side chain (2) both terminal amino and carboxyl groups as well as a three-carbon lin...