Nucleotide synthesis via methods without nucleoside-base protection.

Oligonucleotide synthesis via methods without nucleobase protection (N-unprotected methods) is briefly reviewed. The N-unprotected methods are advantageous in the following respects over conventional approaches that use protectors, generally, acyl protectors for the nucleobase (N-protected method). Two steps, introduction and removal of the protecting groups, are eliminated, and consequently use of undesirable reagents involved in these steps are avoided. In the synthesis of DNA oligomers, the risk of depurination of deoxyadenosine and deoxyguanosine derivatives, which is a serious problem in the N-protected methods, is considerably reduced. The range of synthesizable artificial analogues bearing base-labile functions is extended because harsh base treatment for the deprotection is eliminated.