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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
Author(s) -
Lang Holger,
Gottlieb Margarete,
Schwarz Michael,
Farkas Silke,
Schulz Bernd S.,
Himmelsbach Frank,
Charubala Ramamurthy,
Pfleiderer Wolfgang
Publication year - 1999
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/(sici)1522-2675(19991215)82:12<2172::aid-hlca2172>3.0.co;2-r
Subject(s) - chemistry , oligonucleotide , moiety , acylation , deoxyribonucleosides , hydrolysis , alkyl , alcohol , combinatorial chemistry , stereochemistry , medicinal chemistry , organic chemistry , enzyme , catalysis , dna , biochemistry
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 O 6 ‐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]‐ O 6 ‐[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 O 4 ‐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 ).