Photocleavable protecting groups and methods for their use
View Patent ↗Novel compounds are provided which are useful as linking groups in chemical synthesis, preferably in the solid phase synthesis of oligonucleotides and polypeptides. These compounds are generally photolabile and comprise protecting groups which can be removed by photolysis to unmask a reactive group. The protecting group has the general formula Ar—C(R 1 )(R 2 )—O—C(O)— wherein: Ar is an optionally substituted fused polycyclic aryl or heteroaromatic group or a vinylogous derivative thereof; R 1 and R2 are independently H, optionally substituted alkyl, alkenyl or alkynyl, optionally substituted aryl or optionally substituted heteroaromatic, or a vinylogous derivative of the foregoing; and X is a leaving group, a chemical fragment linked to Ar—C(R 1 )(R 2 )—O—C(O)— via a heteroatom, or a solid support; provided that when Ar is 1-pyrenyl and R 1 and R 2 are H, X is not linked to Ar—C(R 1 )(R 2 )—O—C(O)— via a nitrogen atom. Preferred embodiments are those in which Ar is a fused polycyclic aromatic hydrocarbon and in which the substituents on Ar, R 1 and R 2 are electron donating groups. A particularly preferred protecting group is the “PYMOC” protecting group, pyrenylmethyloxycarbonyl, where Ar is pyrenyl and R 1 and R 2 are H. Also provided is a method of forming, from component molecules, a plurality of compounds on a support, each compound occupying a separate predefined region of the support, using the protected compounds described above.
1. A method of protecting and deprotecting a reactive group in a compound, comprising:
coupling the reactive group with a second compound of the formula Ar—C(R 1 )(R 2 )—O—C(O)—X, wherein:
Ar is an optionally substituted fused polycyclic aryl or heteroaromatic group or a vinylogously substituted species of the foregoing;
R 1 and R 2 are independently H, optionally substituted alkyl, alkenyl or alkynyl, or optionally substituted aryl or heteroaromatic group or a vinylogously substituted derivative of the foregoing; and
X is a leaving group;
provided that when Ar is 1-pyrenyl and R 1 and R 2 are H, the reactive group being protected is not an amine, to provide a protected compound with its reactive group protected by linkage to Ar—C(R 1 )(R 2 )—O—C(O)—; and
irradiating the protected compound to provide a deprotected compound.
2. The method of claim 1 , wherein Ar is independently 1-pyrenyl or 9-anthracenyl, R 1 is hydrogen and R 2 is independently hydrogen, methyl, substituted phenyl, 9-anthracenyl or 1-pyrenyl.
3. A method of protecting and deprotecting a reactive group in a compound, comprising:
coupling the reactive group with a second compound of the formula Ar—C(R 1 )(R 2 )—X, wherein:
Ar is an optionally substituted fused polycyclic aryl or heteroaromatic group or a vinylogously substituted species of the foregoing;
R 1 and R 2 are independently H, optionally substituted alkyl, alkenyl or alkynyl, or optionally substituted aryl or heteroaromatic group or a vinylogously substituted derivative of the foregoing; and
X is a leaving group, to provide a protected compound with its reactive group protected by linkage to Ar—C(R 1 )(R 2 )—O—C(O)—; and
irradiating the protected compound to provide a deprotected compound.
4. The method of claim 3 , wherein Ar is independently 1-pyrenyl or 9-anthracenyl, R 1 is hydrogen and R 2 is independently hydrogen, methyl, substituted phenyl, 9-anthracenyl or 1-pyrenyl.
5. The method of claim 4 , wherein Ar is 1-pyrenyl and R 1 and R 2 are hydrogen.
6. The method of claim 4 , wherein Ar is 9-anthracenyl, R 1 is hydrogen and R 2 is hydrogen.
7. The method of claim 3 , wherein the compound is a ribonucleoside, deoxyribonucleoside or 2′-O-methylribonucleoside.
8. The method of claim 7 , wherein the deoxyribonucleoside is linked to the Ar—C(R 1 )(R 2 )—O—C(O)— group via a 3′ or 5′-OH.
9. The method of claim 3 , wherein the Ar—C(R 1 )(R 2 )—O—C(O)— group is removed by irradiation with light.
10. The method of claim 9 , wherein the wavelength is greater than 340 nm.
11. The method of claim 10 , wherein the wavelength is about 365 nm.