A Versatile Synthetic Approach to Isoguanine Derivatives

Abstract

5-Amino-4-(N-ethoxycarbonyl)formamidino imidazoles were prepared from 5-amino-4-(N-ethoxycarbonyl)cyanoformimidoyl imidazoles and primary alkyl amines, under mild experimental conditions. The product imidazoles were selectively cyclized to N 6 -substituted isoguanines by reflux in acetonitrile with one equivalent of sulfuric acid, followed by neutralization. The same imidazoles led to N 1 -alkylisoguanines as the major product upon reflux in ethanol.

A concise synthesis of isoguanine 2ʹ-deoxyriboside and its adenine-like triplex formation when incorporated into DNA

“…The resulting gel was added to a column of silica gel and the unreacted benzyl alcohol was eluted firstly using CH2Cl2 and then CH2Cl2-MeOH (95:5). Further elution with 10% MeOH-CH2Cl2 afforded the title compound 7 (400 mg, 71%) as a yellow solid; mp 206-209 °C; TLC [MeOH-CH2Cl2 (1:4)]: Rf 0.52; IR (cm -1 ) 3396, 3132, 2937, 1653, 1592; 1…”

“…After stirring (1 h) a white precipitate had formed and the product mixture was concentrated and the residue purified by flash chromatography eluting with EtOAc-CH2Cl2-Et3N (50:50:1) affording an oil which was precipitated from CH2Cl2 (3 mL) into cold hexane (300 mL). The product was dissolved in CH2Cl2 (3 mL) and dried under high vacuum at 30 °C giving the phosphoramidite 15 (0.18 g, 64%) as a colourless viscous oil; mp 59-62 °C; TLC [CH2Cl2-EtOAc-Et3N (50:50:1)]: Rf 0.13; IR (cm -1 ): 3411, 3056, 2968, 1606, 1568; 1…”

“…Although not a DNA base, isoguanine (isoG) occurs naturally and various methods have been reported for the preparation of derivatives [1][2][3][4] including its riboside, 5 2'-deoxyriboside [6][7][8][9] and other analogues. 10,11 Isoguanine has been widely studied and when incorporated into nucleic acids, [12][13][14][15][16][17][18][19][20][21][22][23] has been shown to form stable base pair 7,[24][25][26][27][28] (Figure 1 left) and triplex motifs 29 (Figure 1 middle) as its N1-H tautomer.…”