TY - JOUR
T1 - Automated Synthesis of Oligodeoxyribonucleoside Methylphosphonates Having [N-(3-Aminoprop-1-yl) -N-(2-hydroxyethyl) -2-aminoethyl] Phosphate or Methylphosphonic Acid at the 3′ End Using a Modified Controlled Pore Glass Support
AU - Thaden, John
AU - Miller, Paul S.
PY - 1993/9/1
Y1 - 1993/9/1
N2 - To provide a solid support for automated synthesis of 3′-(aminoalkyl)-modified oligonucleoside methylphosphonates, controlled pore glass beads were functionalized with a protected N-(3-aminopropl-yl)-AT-(2-hydroxyethyl)-2-aminoethyl ester of succinic acid. This “Aha-CPG” was used for automated synthesis of oligo-2′-deoxyribonucleoside methylphosphonates having either of two distinct 3′ terminal modifications. If the first coupling to the beads was of a base-protected 5′-(dimethoxytrityl)-2′-deoxyribonucleoside 3′-(β-cyanoethyl M-N-diisopropylphosphoramidite) synthon, then, upon completion of methylphosphonate oligomer synthesis and deprotection, the 3′-[N-(3-aminoprop-l-yl)-N-(2-hydroxyethyl)-2-aminoethyl] phosphate] derivative of an oligonucleoside methylphosphonate was produced and was shown to be a stable structure which affords a primary alkylamine group suitable as a site for further conjugations. If the first coupling was of a 5′-(dimethoxytrityl)-2′-deoxyribonucleoside 3′-(N,N-diisopropylmethylphosphonamidite) synthon, the initial product of synthesis and deprotection underwent a spontaneous, regiospecific ester cleavage in aqueous solution to produce an oligonucleoside methylphosphonate 3′-(methylphosphonate). An application of the Aha-CPG to the synthesis of rhodamine-conjugated oligonucleoside methylphosphonates is described in a companion paper [Thaden, J. and Miller, P. S. (1993) Bioconjugate Chem, preceding paper in this issue].
AB - To provide a solid support for automated synthesis of 3′-(aminoalkyl)-modified oligonucleoside methylphosphonates, controlled pore glass beads were functionalized with a protected N-(3-aminopropl-yl)-AT-(2-hydroxyethyl)-2-aminoethyl ester of succinic acid. This “Aha-CPG” was used for automated synthesis of oligo-2′-deoxyribonucleoside methylphosphonates having either of two distinct 3′ terminal modifications. If the first coupling to the beads was of a base-protected 5′-(dimethoxytrityl)-2′-deoxyribonucleoside 3′-(β-cyanoethyl M-N-diisopropylphosphoramidite) synthon, then, upon completion of methylphosphonate oligomer synthesis and deprotection, the 3′-[N-(3-aminoprop-l-yl)-N-(2-hydroxyethyl)-2-aminoethyl] phosphate] derivative of an oligonucleoside methylphosphonate was produced and was shown to be a stable structure which affords a primary alkylamine group suitable as a site for further conjugations. If the first coupling was of a 5′-(dimethoxytrityl)-2′-deoxyribonucleoside 3′-(N,N-diisopropylmethylphosphonamidite) synthon, the initial product of synthesis and deprotection underwent a spontaneous, regiospecific ester cleavage in aqueous solution to produce an oligonucleoside methylphosphonate 3′-(methylphosphonate). An application of the Aha-CPG to the synthesis of rhodamine-conjugated oligonucleoside methylphosphonates is described in a companion paper [Thaden, J. and Miller, P. S. (1993) Bioconjugate Chem, preceding paper in this issue].
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U2 - 10.1021/bc00023a015
DO - 10.1021/bc00023a015
M3 - Article
C2 - 8274525
AN - SCOPUS:0027653154
SN - 1043-1802
VL - 4
SP - 395
EP - 401
JO - Bioconjugate Chemistry
JF - Bioconjugate Chemistry
IS - 5
ER -