| Abstract
| - We describe a novel and efficient synthesis (62−84% yields) of the eight possible, diastereomericallypure, cis and trans, R and SO6-allyl-protected N2-dGuo phosphoramidite building blocks derivedthrough cis and trans opening of (±)-3α,4β-dihydroxy-1β,2β-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene [BcPh DE-1 (1)] and (±)-3α,4β-dihydroxy-1α,2α-epoxy-1,2,3,4-tetrahydrobenzo[c]phenanthrene [BcPh DE-2 (2)] by hexafluoropropan-2-ol (HFP)-mediated addition of O6-allyl-3‘,5‘-di-O-(tert-butyldimethylsilyl)-2‘-deoxyguanosine (3) at C-1 of the epoxides. Simply changing therelative amount of HFP used in the reaction mixture can achieve a wide ratio of cis/trans additionproducts. Thus, the observed cis/trans adduct ratio for the reaction of DE-1 (1) in the presence of5 equiv of 3 varied from 17/83 to 91/9 over the range of 5−532 equiv of HFP. The correspondingratios for DE-2 (2) varied from 2/98 to 61/39 under the same set of conditions. When 1 or 2 wasfused with a 20-fold excess of 3 at 140 °C in the absence of solvent HFP, almost exclusive transaddition (>95%) was observed for the both DEs. Through the use of varying amounts of HFP inthe reaction mixture as described above, each of the eight possible phosphoramidite oligonucleotidebuilding blocks (DE-1/DE-2, cis/trans, R/S) of the BcPh DE N2-dGuo adducts can be prepared in anefficient fashion. To rationalize the varying cis-to-trans ratio, we propose that the addition of 3 to1 or 2 in the absence of solvent or in the presence of small amounts of HFP proceeds primarily viaan SN2 mechanism to produce mainly trans-opened adducts. In contrast, increasing amounts ofHFP promote increased participation of an SN1 mechanism involving a relatively stable carbocationwith two possible conformations. One of these conformations reacts with 3 to give mostly transadduct, while the other conformation reacts with 3 to give mostly cis adduct.
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