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), thus 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. Yields are reduced as a result of purification. The end product, although with a lower yield, is much more pure and makes sure that the delivered product is close to 100 % modified.
