Photocleavable Protecting Groups and Methods for Their Use

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(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 compound of the formula Ar—C(R 1 )(R 2 )—O—C(O)—X, wherein:
 Ar is an optionally substituted fused polycyclic aryl or a vinylogous derivative thereof;   R 1  and R 2  are H, optionally substituted alkyl, alkenyl or alkynyl, 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. 
     
     
         2 - 65 . (canceled)