Diarylsulfide backbone containing photolabile protecting groups

Abstract

The present disclosure relates to photoactivable protecting groups containing a diarylsulfide chromophore, a method for the synthesis thereof and their use as photoactivable protecting groups using maskless photolithography based array synthesis.

1 . A compound of the formula 
       
         
           
           
               
               
           
         
         wherein Y is S or O, and 
         A is selected from the group consisting of —CH 2 —, —CH 2 —CH 2 —, —CH(CH 3 )—, —CH(CH 3 )—CH 2 —, and 
         R1 is an unsubstituted or substituted aryl- or heteroaryl-group, and R3 is H, a methyl group or an ethyl group, and 
         wherein R2 is H, forms a phosphoramidite, H-phosphonate or phosphate triester, or 
         wherein R2 is 
       
       
         
           
           
               
               
           
         
         or wherein R2 is 
       
       
         
           
           
               
               
           
         
         wherein R4 is H, forms a phosphoramidite, H-phosphonate or phosphate triester, and 
         wherein R5 is H, OH, a halogen or XR6, wherein X is O or S and R6 is H, an alkyl-group, aryl-group, or OR6 forms a phosphoramidite, phosphodiester, phosphotriester, H-phosphonate or an acetal or silicone moiety, and 
         wherein B is selected from the group consisting of adenine, cytosine, guanine, thymine, uracil, 2,6-diaminopurine-9-yl, hypoxanthin-9-yl, 5-methylcytosinyl-1-yl, 5-amino-4-imidazolecarboxylic acid-1-yl or 5-amino-4-imidazolecarboxylic acid amide-3-yl, wherein when B is adenine, cytosine or guanine the primary amino group optionally has a protecting group or when B is thymine or uracil at the O 4  position is optionally a protecting group, or 
         wherein R 2  is 
       
       
         
           
           
               
               
           
         
         wherein R7 is a natural amino acid, a non-natural amino acid or an amino acid derivative forming an urethan bond to formula Ib, or 
         wherein formula IV represents the carboxy function of a natural amino acid, a non-natural amino acid or an amino acid derivative, forming an ester bond to formula Ib. 
       
     
     
         2 . The compound according to  claim 1  wherein R1 is a phenyl-group, a tert-butyl-phenyl group, a 1- or 2-naphthyl-group, a 2-pyridyl-group an aminophenyl-group, an N-alkylaminophenyl-group, an N-Acylaminophenyl-group, a carboxyphenyl-group, a phenylcarboxylic ester or an amide. 
     
     
         3 . The compound according to  claim 1  wherein A is —CH(CH 3 )—CH 2 —. 
     
     
         4 . The compound according to  claim 1  wherein R2 is a phosphoramidite or —P(OCH 2 CH 2 CN)(N-iPr 2 ). 
     
     
         5 . The compound according to  claim 1  wherein R3 is H or an ethyl group. 
     
     
         6 . The compound according to  claim 1  wherein R4 is H and R5 is H. 
     
     
         7 . The compound according to  claim 1  wherein B is selected from the group consisting of adenine, cytosine, guanine, thymine or uracil. 
     
     
         8 . The compound according to  claim 1  wherein when B is adenine, cytosine or guanine the protecting group is phenoxyacetyl-, 4-tert-butyl-phenoxyacetyl-, 4-isopropyl-phenoxyacetyl- or dimethylformamidino-residues, when B is adenine the protecting group is benzoyl- or p-nitro-phenyl-ethoxy-carbonyl-(p-NPPOC)-residues, when B is guanine the protecting group is isobutyroyl-, p-nitrophenylethyl (p-NPE) or p-NPEOC-residues and when B is cytosine the protecting group is benzoyl-, isobutyryl- or p-NPEOC-residues. 
     
     
         9 . The compound according to  claim 1  wherein R7 is a natural amino acid. 
     
     
         10 . A method for preparing a diarylsulfide backbone containing one or more photolabile protecting group(s) according to  claim 1  comprising the steps of
 a) Provision of p-diethylbenzene as a starting material; 
 b) Bromination of the phenylring; 
 c) Nitration of the obtained compound in Nitric- and Sulfuric Acid in the position para- to the Bromine; 
 d) Purification and crystallization; 
 e) Hydroxymethylation of the compound at the benzylic position; 
 f) Conversion of the aromatic bromine group to the arylsulfide using thiophenol; 
 g) Purification; 
 h) Conversion of the alcohol to chlorocarbonate; and 
 i) Reaction of the chlorocarbonate with a nucleoside and reaction of the nucleoside with a phosphitylating agent, or
 Reaction of the chlorocarbonate with an amino acid derivative. 
 
 
     
     
         11 . The method according to  claim 10 , characterized in that R1 is a phenyl-group, a tert-butyl-phenyl group, a 1- or 2-naphthyl-group or a 2-pyridyl-group. 
     
     
         12 . The method according to  claim 10 , characterized in that A is —CH(CH 3 )—CH 2 —. 
     
     
         13 . The method according to  claim 10 , characterized in that R3 is H or an ethyl group. 
     
     
         14 . A method of forming an array through photolithography, said method comprising contacting a substrate having a site activated by exposure to light with a compound of  claim 1 . 
     
     
         15 . The method of  claim 14  wherein R 2  is 
       
         
           
           
               
               
           
         
         wherein R7 is a natural amino acid, a non-natural amino acid or an amino acid derivative forming an urethan bond to formula Ib, or 
         wherein formula IV represents the carboxy function of a natural amino acid, a non-natural amino acid or an amino acid derivative, forming an ester bond to formula Ib. 
       
     
     
         16 . The method of  claim 14  wherein the contacting of the substrate with a compound of  claim 1  produces a DNA microarray or a peptide microarray. 
     
     
         17 . The method of  claim 16  wherein the method produces a DNA microarray. 
     
     
         18 . The method of  claim 16  wherein the method produces a peptide microarray. 
     
     
         19 . The method of  claim 14  wherein the substrate and/or the compound is activated by exposure to light between the wavelengths of 374 to 405 nm.