Protecting groups acid labile

In peptide synthesis functional groups in the amino acid side chains are often protected with acid-labile protecting groups (Section 4.5.3). The tripeptide in Figure 4.35 contains, for example, a serine ferf-butyl ether and an L-lysine e-protected as an O-tert-butyl carbamate. In the standard strategy of synthesizing oligopeptides from the C- to the N-terminus (cf. Section 6.4.3) the C-terminus is either connected to the acid-labile... 

The side chains of the amino acids in this approach are also protected with acid-labile groups (f-butyl esters and BOC, for example), so that they too are revealed only in the final deprotection step. 

This is the most widely used class of SP linkers. Historically, the SPS of peptides (see Section 2.1) was developed using building blocks protected with acid-labile groups, thus allowing a convenient simultaneous cleavage and deprotection in the final step of the synthesis. Four commercially available acid-labile linkers are depicted in Fig. 1.7 in resin- and compound-bound forms. The preferred cleavage conditions for each linker are also provided. 

Since the Fmoc procedure uses a base for protection of the N-amino group, acid-labile compounds are used to protect the side chains. Side chain protecting compounds generally use a t-butyl moiety such as t-butyl ethers for Ser, Thr, and Tyr t-butyl esters for Asp and Glu and the t-BOC group for His and Lys, respectively. Also, the trityl group is used to protect Cys, Asn, and Gin the 4-methoxy 2,3,6,-trimethylbenzenesulphonyl or the 2,2,5,7,8,-pentamethylChroman-6-sulfonyl... 

O-trimethylsilyl-N-isopropylacrylamide (46a) (Figure 41), and anionically polymerized it with tcrt-BuLi in the presence of trialkylaluminum in toluene. Although the highly isotactic poly(46) (m = 97%) was obtained (Figure 42), the polymerization could not be controlled well in terms of molecular weight and molecular weight distribution. The TMS protective group was labile and was easily removed under mild acidic conditions to afford the objective poly(46) quantitatively. 

Pos twe-Tone Photoresists. The ester, carbonate, and ketal acidolysis reactions which form the basis of most positive tone CA resists are thought to proceed under specific acid catalysis (62). In this mechanism, illustrated in Figure 22 for the hydrolysis of tert-huty acetate (type A l) (63), the first step involves a rapid equihbrium where the proton is transferred between the photogenerated acid and the acid-labile protecting group ... 

The rate of the reaction in such case is R = k [PH ], where P is the reactant (ie, a repeat unit bearing the acid-labile protecting group). 

Fig. 23. Representative protecting groups for phenolic and carboxylic acid-based systems, (a) The polymer-based protecting groups are fisted in order of increasing activation energy for acid-catalyzed deprotection, (b) Acid-labile monomeric dissolution inhibitors, a bifunctional system based on protected bisphenol A. (c) Another system that combines the function of dissolution inhibitor and PAG in a single unit.

In some instances, the resist polymer can be prepared in a single step by direct polymerization of the protected monomer(s) (37,88), entirely avoiding the intermediate PHOST. HOST-containing resist polymers have also been prepared by free-radical copolymerization of a latent HOST and a stable, acid-labile monomer, eg, the copolymerization of acetoxystyrene with tert-huty acrylate, followed by selective removal of the acetoxy group (89) (Fig. 30). 

These were originally prepared by Khorana as selective protective groups for the 5 -OH of nucleosides and nucleotides. They were designed to be more acid-labile than the trityl group because depurination is often a problem in the acid-catalyzed removal of the trityl group. Introduction of p-methoxy groups increases the rate of hydrolysis by about one order of magnitude for each p-methoxy substituent. For 5 -protected uridine derivatives in 80% AcOH, 20°, the time for hydrolysis was... 

This substantial group was developed as a fluorescent, acid-labile protective group for oligonucleotide synthesis. It has properties very similar to those of the DMTr group except that it can be detected down to 10 M on TLC plates with 360-nm ultraviolet light. 

This ester was designed as a base-labile protective group. Monoprotection of aspartic acid was achieved using the DCC/DMAP protocol. Cleavage is... 

Relative Lability of Aspartic Acid )8-Carboxyl Protective Groups ... 

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