Patent ID: 6762298
Filing Date: 2004-07-13
Classification: C07H,Y02P

Abstract:
A method of deprotecting an oligonucleotide, which method comprises heating an oligonucleotide of the formula: in a fluid medium, at a substantially neutral pH, at a temperature up to about 100Â° C. to produce an oligonucleotide of the formula: wherein:R is a thermolabile protecting group of the formula: R1 is H, R1a, OR1a, SR1a or NR1aR1aâ€², wherein R1a and R1aâ€² are the same or different and each is H, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl, or an aralkyl; or, when R1 is NR1aR1aâ€², R1a and R1aâ€², together with the nitrogen atom to which they are bonded, comprise a heterocycle containing from 3 to about 7 atoms in the ring skeleton thereof; X1 is O, S or Se; X is O or S; Z is O, S, NR2a, CR2aR2aâ€² or CR2aR2aCR2bR2bâ€², wherein R2a, R2aâ€², R2b and R2bâ€² are the same or different and each is H, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl, or an aralkyl; or R1a or R1aâ€², in combination with any of R2a, R2aâ€², R2b or R2bâ€², together with C&boxH;X of the protecting group to which they are bonded, comprise a ring containing from 3 to about 7 atoms in the skeleton thereof; provided that R1 is not R1a when Z is S, Z is not CR2aR2aâ€² or CR2aR2aâ€²CR2bR2bâ€² when R1 is SR1a, and Z is not O or S when R1 is H; R2, R2â€², R3 and are the same or different and each is H, an alkyl, an alkenyl, an alkynyl, a cycloalkyl, an aryl, or an aralkyl, or R2 or R2â€², in combination wit R3 or R3â€², together with the carbon atoms to which they are bonded, comprise a cyclic substituent of the formula: wherein p is an integer from 0-6 and a-d are the same or different and each is selected from the group consisting of H, an alkyl, a nitro, a dialkylamino, an alkoxy, an alkylthio, a cyano and a halogen, provided that the aromatic ring, which bears substituents a-d, is one carbon removed from the phosphate oxygen of formula (IIIa), wherein R1, R2a, R2aâ€², R2b, R2bâ€², R2, R2â€², R3 or R3â€² is unsubstituted or substituted with one or more substituents, which are the same or different, selected from the group consisting of OR8, CN, NO2, N3, and a halogen, wherein R8 is H or an alkyl; R4 and R15 are the same or different and each is H, a hydroxyl protecting group, or a solid support; Q1 is a nucleoside, an oligonucleotide or an oligomer comprising an oligonucleotide; n is an integer from 1 to about 300; and Q is a nucleoside, an oligonucleotide or an oligomer comprising an oligonucleotide and, when n is greater than 1, each Q is independently selected, provided that the deprotection is not by an enzyme.