Notes: Formation of Cyclopropane Derivatives from 4-Bromocrotonic Esters

Transient protection. 2. One-flask synthesis of 6-O-[(4-nitrophenyl)ethyl]-2'-deoxyguanosine nucleosides

“…The degradation of guanine nucleosides during oligonucleotide synthesis is a well known phenomenon.1 5The findings by Reese2,3 and by Hata4,5 that guanine residues are subject to both O6 sulfonylation with condensing reagents and to O6 phosphorylation with activated nucleotides implicated the O6 position as the source of this degradation. We then devised a sulfonylation/displacement route for specific O6 alkylation of deoxyguanosine and showed that O6 protection with any of several /3-substituted ethyl derivatives completely eliminated reaction of the base with condensing agents.6 Moreover, we reported use of three of these protecting groups, the (nitrophenyl)ethyl, cyanoethyl, and (phenylthio)ethyl groups, in the syntheses of several short oligonucleotides.7"9…”

“…The solid product was dissolved in water (100 mL) and extracted successively with 50 mL of toluene and 50 mL of ether to remove less polar impurities and then with 3 X 50 mL of CH2C12. The CH2C12 extract was purified by chromatography on silica using a gradient of methanol (0-5% (v/v)) in CHC13 as eluent to give 10, which was recrystallized from ether/methanol (0.42 g, 18%): mp 164-169 °C; MS (CH4, Cl), m/e (relative intensity) 581 (40, + 1), 536 (8, + 1 -Me2NH2), 508 (19, (M +1 -DMF) + 1) [typical fragments of tartar amide crown ethers], 5,8,15 (2 R ,3R,lljR,4,10,3,11,. The tetraamide 10 (130 mg, 0.22 mmol) was dissolved in 2 mL of D20, 200 ph of concentrated HC1 was added, and the mixture was heated at 80 °C for 18 h. NMR showed complete loss of methyl amide resonances.…”