Synthesis and Characterization of Thermodynamically Unstable Polycyclic Aromatic Hydrocarbon Episulfides and Episulfoxides

Synthesis of Conformationally Locked Carbocyclic Nucleosides Built on a Thiabicyclo[3.1.0]hexane System as a Pseudosugar Surrogate

“…Once these precursors for thiirane preparation were at hand, the appropriate method to transform the epoxy group into a thiirane ring was validated. Attempts to convert compound 17 into the thiirane 22 were made under a variety of conditions, for example, by treatment with dif-ferent sulfur-containing reagents such as potassium thiocyanate in water/methanol, [17,18] thiourea, [19] N,N-dimethylthioformamide, [20] ammonium thiocyanate with tert-butyl alcohol as a solvent in the presence of ceric ammonium nitrate [21] and ammonium thiocyanate in acetonitrile in the presence of ruthenium trichloride. [22] Another interesting method was the preparation of thiiranes via the corresponding 2-chloroalkyl 2Ј,4Ј-dinitrophenyl sulfides, which could be easily prepared from the corresponding alkene.…”

“…Owing to the incompatibility of an epoxy group adjacent to a pyrimidine base, it was thought that the isosteric replacement of the cyclopropyl moiety with a thiirane group would be more appropriate. The preparation of carbanucleosides, especially pyrimidine derivatives, built on a thiabicyclo[3.1.0]hexane system is not a trivial task for a number of reasons: 1) the existing methods for the introduction of an episulfide into a five-membered ring are associated with extremely low reaction yields making them impractical from a synthetic point of view; [17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] 2) when an epoxy group is present in the vicinity of a pyrimidine heterocyclic base, an intramolecular attack by the enol of the base takes place to produce epoxy ring-opening; 3) as epoxides and thiiranes exhibit similar chemical properties, there is also a risk of episulfide ring-opening.…”