Synthesis cleavage

Amide derivatives of benzothiazepinone 108 were prepared by solid-phase synthesis. Cleavage of 108 from the A-methylbenzhydryl (MBHA) resin was done with HF/anisole (Figure 13) <1999TL4939>. 

Automated synthesis of peptide and oligonucleotide libraries was initiated about 10 years ago [4], Within the last three years, there has been much attention focused on the generation of combinatorial libraries of small molecules. As with biopolymers, the use of solid resin support was central to the advance of this field. In solid-phase synthesis, one of the reactants is covalently bound to the solid support and an excess of the other reactants may be used in each step to drive reactions to completion. Purification of the intermediates and final product is easily achieved through extensive washing of the resin after each chemical step. For the purpose of high throughput synthesis, cleavage of the final... 

In the tert-butoxycarbonyl (Boc) strategy for solid-phase peptide synthesis, cleavage from the solid-phase and side-chain deprotection is performed with strong acids such as hydrogen fluoride. Treatment of a glycopeptide with strong acid results in partial or, in most cases, complete cleavage... 

The trityl linkers were introduced to permit anchoring of carboxylic acids and other nucleophiles to a solid support and to effect cleavage reactions under very mild acidic conditions [64-67]. Various trityl resins, such as Ib-le (Table 1), have been developed that differ in the substitution pattern of the aromatic ring substituents in order to modify the cleavage properties by their influence on the stability of the trityl cation. For carboxylic acids, amines, and phenols, the chlorotrityl resin Ic affords a more stable anchor [65-67] than does resin lb. Similarly, resin le, which contains both fluoro and carbonyl ring substituents, proved to be very stable toward nucleophiles and was fully compatible with piperidine / / -Fmoc (9-fluorenylmethoxycar-bonyl) deprotections used in a model peptide synthesis. Cleavage of acids from le could be effected using dilute TFA in dichloromethane [68]. 

Figure 1.28 Combination of solid-phase synthesis, cleavage, and microprinting to glass slides.

Phenyl esters are suggested for carboxyl protection in peptide synthesis cleavage is achieved under mild conditions without racemization by treatment with hydrogen peroxide. Such enhanced nucleophilicity of peroxy-anions is ascribed to the a-effect of the unshared pair of electrons on the atom adjacent to the nucleophilic atom, and this phenomenon has been studied further. ... 

Warnecke, A., Eichtner, I., Sass, G. and Kratz, E. (2007) Synthesis, cleavage profile, and antitumor efficacy of an albumin-binding prodrug of methotrexate that is cleaved by plasmin and cathepsin B.Archiv Der Pharmazie, 340, 389-395. 

In another example, the phosphoramidite 41 with a biotin moiety linked through a silyl diether linkage was coupled to the 5 -end of oligonucleotide on a solid support (eq 23). After synthesis, cleavage, and deprotection, the oligonucleotide 42 that contained... 

J. Schwarz - Organozirconium Compounds in Organic Synthesis Cleavage Reactions of Carbon-Zirconium Bonds, Pure Appl. Chem. 52,733,1980. 

At the end of the synthesis, cleavage from the support and complete deprotection of the oligonucleotide are effected by a three-step procedure, and are the same for a synthesis on controlled pore glass or the polyamide support. 

Fig. 6 Example of the synthesis, cleavage, and purification of a thioester containing peptide...

Giegrich, H., Eisele-Buhler, S., Hermann, C., Kvasyuk, E., Charubala, R., and Rfleiderer, W., New photolabile protecting groups in nucleoside and nucleotide chemistry synthesis, cleavage mechanisms and applications, Nucleosides Nucleotides, 17, 1987-1996, 1998. 

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