Protective Groups Cleavable by Acids

Benzyl ethers bearing electron-donating groups can be cleaved by treatment with acids or oxidants. The rate of solvolysis increases with the number of electron-donating groups, and in the series benzyl benzhydryl trityl. For the solid-phase synthesis of oligonucleotides, the 5 -hydroxyl group is usually protected as 4,4/-dimethoxytrityl 

As an alternative to protection as ethers, alcohols can also be protected as acetals, the most common being tetrahydropyranyl ethers (THP-OR) and 1-ethoxyethyl ethers (EE-OR) (Table 7.7). Support-bound secondary aliphatic alcohols have been 

TsOH (2% in DCM), 5x5 min (TsOH was dissolved in MeOH and diluted with DCM) 

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The combination of very mild coupling and deprotection protocols provides the flexibility needed in order to incorporate a variety of side-chain-protecting groups, cleavable by acid (Boc), base (Fmoc), Pd(II) (Aloc)J43 or nucleophiles (Dde)J441 Linear precursors of such templates with four orthogonally protected lysine residues are generally obtained in yields around 80% and cyclization proceeds quickly at high dilution almost quantitatively. 

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