Phosphoramidite I (1, R = iPr) useful as phosphorylation reagent in oligonucleotide syntheses, were prepd. by monomethoxytrityl protection of 4-hydroxybenzaldehyde with subsequent borohydride redn. and phosphorylation with 2-cyanomethyl N,N-diisopropylphosphoroamidochloridite. In an example, reaction of 5.08 g of 4-hydroxybenzaldehyde with 1.0 g of 4-methoxytriphenylmethyl chloride in 10 mL of dichloromethane in the presence of 2.2 mL of EtNiPr2 at 20° for 6 h gave the protected benzaldehyde, which was reduced with 0.25 g of NaBH4 in 10 mL of THF for 6 h at 20°, giving the protected benzyl alc., 4-MMTO-C6H4CH2OH with 85% yield. The obtained product (0.23 g) was reacted with 0.2 mL of phosphoramidochloridite NCCH2CH2OP(Cl)NiPr2in the presence of 0.4 mL of EtNiPr2 in 5 mL of CH2Cl2, giving the product 1 with 87% yield.
New phosphoramidite reagent for phosphorylation of synthetic oligonucleotides in terminal position / Di Fabio, Giovanni; Zarrelli, Armando. - (2016).
New phosphoramidite reagent for phosphorylation of synthetic oligonucleotides in terminal position
Di Fabio, Giovanni
;Zarrelli, Armando
2016
Abstract
Phosphoramidite I (1, R = iPr) useful as phosphorylation reagent in oligonucleotide syntheses, were prepd. by monomethoxytrityl protection of 4-hydroxybenzaldehyde with subsequent borohydride redn. and phosphorylation with 2-cyanomethyl N,N-diisopropylphosphoroamidochloridite. In an example, reaction of 5.08 g of 4-hydroxybenzaldehyde with 1.0 g of 4-methoxytriphenylmethyl chloride in 10 mL of dichloromethane in the presence of 2.2 mL of EtNiPr2 at 20° for 6 h gave the protected benzaldehyde, which was reduced with 0.25 g of NaBH4 in 10 mL of THF for 6 h at 20°, giving the protected benzyl alc., 4-MMTO-C6H4CH2OH with 85% yield. The obtained product (0.23 g) was reacted with 0.2 mL of phosphoramidochloridite NCCH2CH2OP(Cl)NiPr2in the presence of 0.4 mL of EtNiPr2 in 5 mL of CH2Cl2, giving the product 1 with 87% yield.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.