Why are the yields lower for modified oligos?
Many of the modified amidites are less stable and do not couple as efficiently as the unmodified bases (even though longer coupling procedures may be used). Therefore, failure sequences are more abundant than in normal synthesis. Consequently, most of the modified oligos should be purified by HPLC to remove the more abundant failure sequences. Final yields are reduced as a result of the purification step, which results in a much purer final product, nearly 100% modified.