Nucleotides, Part LXIII, New 2-(4-Nitrophenyl)ethyl(Npe)- and 2-(4-Nitrophenyl)ethoxycarbonyl(Npeoc)-Protected 2′-Deoxyribonucleosides and Their 3′-Phosphoramidites - Versatile Building Blocks for Oligonucleotide Synthesis

• Published in: Helvetica chimica acta Vol. 82; no. 12; pp. 2172 - 2185
• Main Authors: Lang, Holger, Gottlieb, Margarete, Schwarz, Michael, Farkas, Silke, Schulz, Bernd S., Himmelsbach, Frank, Charubala, Ramamurthy, Pfleiderer, Wolfgang
• Format: Journal Article
• Language: English
• Published: Basel Verlag Helvetica Chimica Acta 15.12.1999
• ISSN: 0018-019X; 1522-2675
• DOI: 10.1002/(SICI)1522-2675(19991215)82:12<2172::AID-HLCA2172>3.0.CO;2-R

A series of new base‐protected and 5′‐O‐(4‐monomethoxytrityl)‐ or 5′‐O‐(4,4′‐dimethoxytrityl)‐substituted 3′‐(2‐cyanoethyl diisopropylphosphoramidites) and 3′‐[2‐(4‐nitrophenyl)ethyl diisopropylphosphoramidites] 52 – 66 and 67 – 82, respectively, are prepared as potential building blocks for oligonucleotide synthesis (see Scheme). Thus, 3′,5′‐di‐O‐acyl‐ and N 2,3′‐O,5′‐O‐triacyl‐2′‐deoxyguanosines can easily be converted into the corresponding O6‐alkyl derivatives 6, 8, 10, 12, 14, and 16 by a Mitsunobu reaction using the appropriate alcohol. Mild hydrolysis removes the acyl groups from the sugar moiety (→ 9, 11, 13, 15, and 19 (via 18), resp.) which can then be tritylated (→ 38 – 42) and phosphitylated (→ 57 – 61) in the usual manner. N 2‐[2‐(4‐nitrophenyl)ethoxycarbonyl]‐substituted and N 2‐[2‐(4‐nitrophenyl)ethoxycarbonyl]‐O6‐[2‐(4‐nitrophenyl)ethyl]‐substituted 2′‐deoxyguanosines 5 and 7, respectively, are synthesized as new starting materials for tritylation (→ 28, 35, and 37) and phosphitylation (→ 54, 56, 70, and 78). Various O4‐alkylthymidines (see 20 – 24) are also converted to their 5′‐O‐dimethoxytrityl derivatives (see 43 – 47) and the corresponding phosphoramidites (see 62 – 66 and 79 – 82).