Pii: S0040-4039(99)01563-4

The 9-phenylthioxanthyl (S-pixyl or S-Px) group has been investigated as a photocleavable protecting group for primary alcohols, and specifically as a 5' hydroxy protecting group for deoxyribonucleosides. Several alcohols, including the four nucleosides with protected exocyclic amino functions, were protected in very good to excellent yield by treatment of 9-chloro-9-phenylthioxanthene 3 in dry pyridine to reveal the derivatized compounds. Irradiation of the protected substrates in neutral, aqueous solution regenerated the starting alcohols in excellent yield. © 1999 Elsevier Science Ltd. All rights reserved. Key. words: protecting groups; photochemistry; nucleosides; alcohols. The extensive utility of oligonucleotides in applications ranging from DNA sequencing to antisense drugs has led to progressive advances in techniques used in their manufacture. 1,2 The efficient production of oligonucleotides is now possible using synthetic protocols that are nearly as well established as those used in solid-phase peptide synthesis. This simplicity in handling combined with the undeniable utility of oligonucleotides has led to their very creative use in combinatorial chemistry. 3'4 Such advances have produced a high demand for new protective schemes for the 5' hydroxy function of nucleic acids, a key step in the synthesis of oligonucleotides via the phosphoramidite approach. 2 The regioselective protection of the primary hydroxyl function in the presence of other secondary hydroxyl groups in nucleosides is a high priority when choosing a protective scheme. 2 Further, a 5' protective scheme must be orthogonal with the current protocols of solid-phase oligonucleotide synthesis, 5 such as protection of the exocyclic amino function of the DNA bases. The use of low energy UV light as a reactive medium to selectively deprotect a 5' protecting group in the presence of other protective schemes is very advantageous in that one can avoid the acid-catalyzed depurination of a nucleic acid that has been observed with the use of several acid-labile 5' protecting groups. 6 In addition, one very exciting advantage from a synthetic perspective is the ability to use light to spatially control reactions within well-defined regions. * Corresponding author. Tel: 773-508-3174; fax: 773-508-3086; e-mail: [email protected] 0040-4039/99/$ see front mauer © 1999 Elsevier Science Ltd. All rights reserved. PII: S0040-4039(99)01563-4