N-protecting groups for 5'-amino-modifiers can be problematic in automated synthesis. DMT protection is frequently too labile for the amino group. MMT is usually preferred for its greater stability as an N-protecting group, however, it has two practical disadvantages: (1) It requires a custom deprotection protocol since NH-MMT is slightly more robust than O-DMT. (2) Automated synthesizers are designed to quantify DMT cleavage, not MMT cleavage. While the aforementioned Fmoc protected 5'-amino-modifiers offer one potential solution to these disadvantages, sometimes it is preferable to have acid-labile N-protection.
BA0324 has a novel N-protecting group that is based upon colorimetric-oxycarbonyl (Cmoc). In essence, the Cmoc group is an O-DMT that is tethered to an N-bis(4-chlorophenyl)-methoxycarbonyl protecting group. Both protecting groups are acid labile, but only the DMT cation generates a colorimetric signal because the tether quenches the bis(4-chlorophenyl)-methyl-carbocation in an intra-molecular fashion, affording a neutral tetrahydrofuran derivative.
The acid lability of the Cmoc group allows the choice between on-column deprotection, and off column deprotection. Being more lipophilic than a traditional DMT group, the Cmoc protecting group does an excellent job in facilitating SPE purification of full length oligos. Users who prefer the DMT-on purification strategy will similarly find utility in the Cmoc-on purification strategy.