Studies on the Synthesis of S^5′,6-Methano-5′-Thiourldines

REFERENCES

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• In an alternative mechanism, kindly suggested by a reviewer, the enolate anion derived from the 5-acetoxy group could facilitate the displacement reaction via intermediates of the following type
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• Benzoylation was accomplished with benzoic anhydride because use of benzoyl chloride leads to a mixture of 9 and the bis-benzoylated-5′-chloro nucleoside formed by cleavage of the 2,5′-anhydro linkage. Other examples that illustrate the marked susceptibility of the anhydro linkage to ring opening include the unexpected formation of the 5′-Otosyl nucleoside when 5-hydroxy-6-hydroxymethyl-2′,3′-O-isopropylidene-2,5′-anhydrouridine (8, but R = H) is treated with ptoluenesulfonic acid and acetone in order to form the 5,743 isopropylidene compound. Similarly, 8 (R = OAc) undergoes cleavage on treatment with silver trifluoroacetate in pyridine at room temperature to afford an intermediate ester that hydrolyzes during aqueous work-up to give the 5′-unsubstituted product. This latter reaction represents a new method for converting 2,5′-anhydro nucleosides into the parent alcohols under very mild conditions
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• Molecular modeling studies using the Hyperchem™ . implementation of the MM2 force field were conducted along the lines described earlier.2 The three low energy structures found have the following conformational parameters: 3a (2′-exo form), 20.8 Kcal, γ (S5′, C5′, C4′, C3′) = 62°, χ (O4′-C1′-N1-C2) = −173° 3a (3′-exo form), 19.2 Kcal, γ = 72°, χ = −156° 3b (4′-endo form), 19.1 Kcal, γ = 165° χ = 179°
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