Protecting groups base labile

In the Fmoc protection approach, the acid-labile ferf-butyl groups are often used for side-chain protection. The base-labile Fmoc groups can be easily removed during a synthesis using piperidine (Fig. 4). The final global deprotection together with cleavage from the polymeric support is achieved with TFA. 

In the final product there is scrambling of label between the 17 and 15 positions. The strongly basic conditions required in the Wittig reaction necessitate the protection of base-labile groups. Thus the 3- and 13-hydroxy groups can be converted to trimethylsilyl ethers (38) or tetrahydropyranyl ethers which are then easily removed by mild acid treatment. 

Sulfides are oxidized to sulfoxides. One application of this reaction is the removal of a benzylthioethyl group from protected oligosaccharides. The oxidation makes the group base-labile. When the sulfide is coordinated to a metal that also bears chiral ligands, the oxidation becomes enantioselective. ... 

The N-Fmoc protecting group is labile to organic bases and is removed by base-catalyzed elimination (Scheme 20.2). Deprotection is most efficient with unhindered secondary amines, but is also susceptible to primary and tertiary amines. Typically, a 20% piperidine in DMF solution is used to form a dibenzofulvene (DBF) intermediate that is immediately trapped by the secondary amine to form an inert adduct. 

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.

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

The Bnpeoc group was developed as a base-labile protective group for solid-phase peptide synthesis. The carbamate is formed from the O-succinimide (DMF, 10% Na2C03 or 5% NaHC03) and is cleaved using DBN, DBU, DBU/AcOH, or piperidine. ... 

The Dnseoc group was developed as a base-labile protective group for the 5 -hydroxyl in oligonucleotide synthesis. It is cleaved with DBU in aprotic solvents. The condensation of oligonucleotide synthesis can be monitored by UV detection at 350 nm or by fluorescence at 530 nm of the liberated vinylsulfone. ... 

A variety of cleavage conditions have been reported for the release of amines from a solid support. Triazene linker 52 prepared from Merrifield resin in three steps was used for the solid-phase synthesis of aliphatic amines (Scheme 22) [61]. The triazenes were stable to basic conditions and the amino products were released in high yields upon treatment with mild acids. Alternatively, base labile linker 53 synthesized from a-bromo-p-toluic acid in two steps was used to anchor amino functions (Scheme 23) [62]. Cleavage was accomplished by oxidation of the thioether to the sulfone with m-chloroperbenzoic acid followed by 13-elimination with a 10% solution of NH4OH in 2,2,2-trifluoroethanol. A linker based on l-(4,4 -dimethyl-2,6-dioxocyclohexylidene)ethyl (Dde) primary amine protecting group was developed for attaching amino functions (Scheme 24) [65]. Linker 54 was stable to both acidic and basic conditions and the final products were cleaved from the resin by treatment with hydrazine or transamination with ra-propylamine. 

Aliphatic and aromatic carboxamides, with the exception of p-nitrobenzamide, are dehydrated in this way in high yield. Acid-labile protective groups such as tetra-hydropyranyl and tert-butyldimethylsilyl ether and base-sensitive compounds are not attacked. A,A -Sulfinyldi-1,2,4-triazole, easily prepared from thionylchloride and triazole [THF, (C2H5)3N, 0 °C, 1 h] in 85-95% yield, was used without further purification. 

De Visser PC, van Helden M, Filippov DV, van der Marel GA, Drijfhout JW, van Boom JH, Noort D, Overkleeft HS (2003) A novel, Base-Labile Fluorous Amine Protecting Group Synthesis and Use as a Tag in the Purification of Synthetic Peptides. Tetrahedron Lett 44 9013-9016... 

The synthesis of lipidated peptides is implicated by the base-lability of the thioester and the acid sensitivity of the prenyl group double bonds. Thus, new protecting groups are required which can be removed under extremely mild, preferably neutral, conditions. 

The base lability of succinoyl diester hnker severely limits the selection of protecting groups available for an oligosaccharide synthesis, so a more versatile tether was required. Diether bonds of benzylphenol or dibenzyl of 1,4-di(hydroxymethyl)-benzene satisfy this requirement because they are stable to both bases and to acids. A sufficient acid stability is important since the formation of a glycosidic bond is an acid-catalyzed reaction, not surprisingly, as it is an acetal functionality. For instance, DOX,34 the dibenzyl hnker a,a -DiOxyXylyl diether, -0CH2C6H4CH20-, is not limited by restriction of the succinoyl hnker (1) when bound via a hydroxyl or as an... 

CGJ Verhardt, GI Tesser. New base-labile amino-protecting groups for peptide synthesis. Rec Trav Chim Pays-Bas 107, 621, 1988. 

VV Samukov, AN Sabirov, PI Pozdnyakov. 2-(4-Nitrophenyl)sulfonylethoxycarbonyl (Nsc) group as a base-labile a-amino protection for solid phase peptide synthesis. Tetrahedron Lett 35, 7821, 1994. 

T lohnson, RC Sheppard. A new t-butyl-based acid-labile protecting group for the guanidine function of Na-11 uorcnyI mcthyoxycarbonyl -argi n i nc. (Btb) J Chem Soc Chem Commun 1605, 1990. 

The group of allyl-based linkers was developed by Kunz et al. [49] Linkers of the general allyl type are particularly valuable, because they are removable under almost neutral conditions using palladium catalysis and are orthogonally stable towards the commonly used acid and base-labile protecting groups (Tab. 3.2). 

Initially, the Boc group was used for reversible a-amine protection and most side-chain functional groups were protected as benzyl derivatives, which are stable to Boc removal in HC1 or TFA. This Boc/Bzl strategy is still frequently used and is the method of choice in several laboratories. It has, however, been replaced in many laboratories by the base-labile Fmoc group, which allows weak acid deprotection of tert-butyl groups from the side chains. For short- and moderate-sized peptides both systems are effective. For protein synthesis, the relative merits have not yet been fully established. 

An interesting approach based entirely on the solid-phase route has been reported for the synthesis of a-conotoxin SI (Scheme 14) where a combination of acid-labile and acid-stable thiol protecting groups are employed for the required orthogonality.[107]... 

Alternatively, both peptide chains could be protected at one cysteine residue as a 5-Acm derivative and at the second cysteine residue by an acid-labile [Trt, Mob, Xan, or Bzl(4-Me)], base-labile (Fm), or reduction-labile (5-tBu) group. Both peptide chains may then be separately converted into the free thiol/Acm-protected form for selective activation of one chain as S-SPy or. S -Npys derivatives by reaction with di(2-pyridyl)disulfide or di[5-nitro(2-pyridyl)]disulfide, or as a sulfenohydrazide derivative by reaction with azodicarbocylic acid derivatives for formation of the first interchain disulfide bridge. 

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