Process for preparing oligonucleotides using silyl-containing diamino phosphorous reagents

A synthetic process comprising contacting a compound having formula II with a compound having formula III:

• ##STR12## for a time and under reaction conditions effective to form a compound having formula IV:
• ##STR13## wherein:
• each Q is O;
• each B.sub.X is, independently, a nucleosidic base;
• each X is, independently, H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF.sub.3, OCF.sub.3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SOCH.sub.3, SO.sub.2 CH.sub.3, ONO.sub.2, NO.sub.2, N.sub.3, NH.sub.2, heterocycloalkyl, or substituted silyl;
• R.sub.HP is a hydroxyl protecting group;
• each R.sub.N is, independently, alkyl having 1 to about 10 carbon atoms;
• each R.sub.S is, independently, alkyl having 1 to about 10 carbon atoms or aryl having 6 to about 10 carbon atoms;
• (P) is H, a hydroxyl protecting group or a solid support;
• and
• x is 1 to about 7.

A synthetic process comprising the steps of:

• contacting a compound having formula I with a silylalkyl coupling reagent having formula .sub.2 PO(CH.sub.2).sub.X Si(R.sub.S).sub.3 for a time and under reaction conditions effective to form a compound having formula II:
• ##STR16## wherein:
• each Q is O;
• each B.sub.X is, independently, a nucleosidic base;
• each X is, independently, H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF.sub.3, OCF.sub.3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SOCH.sub.3, SO.sub.2 CH.sub.3, ONO.sub.2, NO.sub.2, N.sub.3, NH.sub.2, or substituted silyl;
• R.sub.HP is a hydroxyl protecting group;
• each R.sub.N is , independently, alkyl having 1 to about 10 carbon atoms;
• each R.sub.S is, independently, alkyl having 1 to about 10 carbon atoms or aryl having 6 to about 10 carbon atoms;
• and
• x is 1 to about 7;
• contacting said compound having formula II with a compound having formula III for a time and under reaction conditions effective to form a compound having formula IV:
• ##STR17## wherein (P) is H, a hydroxyl protecting group or a solid support;
• contacting said compound having formula IV with an oxidizing agent for a time and under reaction conditions effective to form a compound having formula V:
• ##STR18## wherein Z is O or S;
• exposing said compound having formula V to conditions effective to remove said R.sub.HP group;
• contacting said compound having said R.sub.HP group removed therefrom with a compound having formula II to form a compound having formula Va:
• ##STR19## where n=1 ;
• contacting said compound having formula Va with an oxidizing agent for a time and under reaction conditions effective to form an oxidized compound having formula Va1:
• ##STR20## and contacting said oxidized compound having formula Va1 with aqueous base or fluoride ion to remove said silylalkyl phosphate protecting groups.

A synthetic process comprising contacting a compound having formula:

• ##STR21## with aqueous base or fluoride ion to remove a silylalkyl phosphate protecting group therefrom, wherein:
• each Q is O;
• each B.sub.X is, independently, a nucleosidic base;
• each X is, independently, H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF.sub.3, OCF.sub.3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SOCH.sub.3, SO.sub.2 CH.sub.3, ONO.sub.2, NO.sub.2, N.sub.3, NH.sub.2, or substituted silyl;
• R.sub.HP is a hydroxyl protecting group;
• each R.sub.N is, independently, alkyl having 1 to about 10 carbon atoms;
• each R.sub.S is, independently, alkyl having 1 to about 10 carbon atoms or aryl having 6 to about 10 carbon atoms;
• and
• x is 1 to about 7;
• Z is O or S;
• and
• (P) is H, a hydroxyl protecting group or a solid support.

A synthetic process comprising contacting a compound having formula:

• ##STR22## with aqueous base or fluoride ion to remove silylalkyl phosphate protecting groups therefrom, wherein:
• each Q is O
• each B.sub.X is, independently, a nucleosidic base;
• each X is, independently, H, OH, alkyl, substituted alkyl, alkaryl or aralkyl, F, Cl, Br, CN, CF.sub.3, OCF.sub.3, OCN, O-alkyl, S-alkyl, N-alkyl, O-alkenyl, S-alkenyl, N-alkenyl, SOCH.sub.3, SO.sub.2 CH.sub.3, ONO.sub.3, NO.sub.3, N.sub.3, NH.sub.2, or substituted silyl;
• R.sub.HP is a hydroxyl protecting group;
• each R.sub.N is, independently, alkyl having 1 to about 10 carbon atoms;
• each R.sub.5 is, independently, alkyl having 1 to about 10 carbon atoms or aryl having 6 to about 10 carbon atoms;
• and
• x is 1 to about 7;
• Z is O or S;
• (P) is H, a hydroxyl protecting group or a solid support;
• and
• n is 2-200.