Photocleavable protecting groups and methods for their use
First Claim
1. A compound of the formula Ar--C(R1)(R2)--O--C(O)--X, wherein:
- Ar is an optionally substituted fused polycyclic aryl or a vinylogous, derivative thereof;
R1 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(R1)(R2)--O--C(O) via a heteroatom, or a solid support;
provided that when Ar is 1-pyrenyl and R1 and R2 are H, X is not linked to Ar--C(R1)(R2)--O--C(O)-- via a nitrogen atom.
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Abstract
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(R1)(R2)--O--C(O)-- wherein:
Ar is an optionally substituted fused polycyclic aryl or heteroaromatic group or a vinylogous derivative thereof;
R1 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(R1)(R2)--O--C(O)-- via a heteroatom, or a solid support; provided that when Ar is 1-pyrenyl and R1 and R2 are H, X is not linked to Ar--C(R1)(R2)--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, R1 and R2 are electron donating groups. A particularly preferred protecting group is the "PYMOC" protecting group, pyrenylmethyloxycarbonyl, where Ar is pyrenyl and R1 and R2 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.
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Citations
30 Claims
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1. A compound of the formula Ar--C(R1)(R2)--O--C(O)--X, wherein:
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Ar is an optionally substituted fused polycyclic aryl or a vinylogous, derivative thereof; R1 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(R1)(R2)--O--C(O) via a heteroatom, or a solid support; provided that when Ar is 1-pyrenyl and R1 and R2 are H, X is not linked to Ar--C(R1)(R2)--O--C(O)-- via a nitrogen atom. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 15, 16, 17, 18, 19, 20, 23, 24, 25, 26, 27, 28, 29, 30)
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11. A method of making a compound of the formula Ar--C(R1)(R2)--O--C(O)--N, wherein Ar is 1-pyrenyl;
- R1 and R2 are H; and
N is a base-protected nucleoside, wherein the nucleoside has a base selected from the group consisting of adenine, cytosine, guanine, thymine, uracil or an analog thereof and the base is linked to a ribose, a 2'"'"'-O-alkylribose, a 2'"'"'-O-allylribose, a 2'"'"'-deoxyribose, a 2'"'"'-deoxy-2'"'"'-fluororibose, or a 2'"'"'-deoxy-2'"'"'-bromoribose;
the method comprising the steps of;(a) acylating the 5'"'"'-OH of the base-protected nucleoside with pentafluorophenoxy chloroformate to provide a 5'"'"'-O-C(O)--pentafluorophenoxy base-protected nucleoside; (b) reacting the 5'"'"'-O-C(O)-pentafluorophenoxy base-protected nucleoside with 1-pyrenyl methyl carbinol to provide a compound of the formula Ar--C(R1)(R2)--O--C(O)--N. - View Dependent Claims (13, 21)
- R1 and R2 are H; and
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12. A method of making a compound of the formula Ar--C(R1)(R2)--O--C(O)--N, wherein Ar is 9-anthracenyl;
- R1 and R2 are H; and
N is a base-protected nucleoside, wherein the nucleoside has a base selected from the group consisting of adenine, cytosine, guanine, thymine, uracil or an analog thereof and the base is linked to a ribose, a 2'"'"'-O-alkylribose, a 2'"'"'-O-allylribose, a 2'"'"'-deoxyribose, a 2'"'"'-deoxy-2'"'"'-fluororibose, or a 2'"'"'-deoxy-2'"'"'-bromoribose;
the method comprising the steps of;(a) acylating the 5'"'"'-OH of the base protected nucleoside with pentafluorophenoxy chloroformate to provide a 5'"'"'-O-C(O)-pentafluorophenoxy base-protected nucleoside; (b) reacting the 5'"'"'-O-C(O)-pentafluorophenoxy base-protected nucleoside with 9-anthracenyl methyl carbinol to provide a compound of the formula Ar--C(R1)(R2)--O--C(O)--N. - View Dependent Claims (14, 22)
- R1 and R2 are H; and
Specification