Benzoyl groups, solid-phase synthesis

Welz et al. developed a procedure for synthesis of oligoribonucleotides based on application of tetrazole for activation of RNA phosphoramidites in automated solid-phase synthesis <2000MB934>. Ar-Benzoyl tetrazole has been developed as a mild and selective reagent for monobenzoylation of the exocyclic amino group in nucleic acid bases <1997TL8811>. An improved procedure is described for the efficient and high yield (76-91%) synthesis of... 

A potential problem in the coupling of S-acyl or S-alkoxy-carbonyl-L-cysteine derivatives to other -blocked amino acids is S - iV-acyl migration which results from the presence of the free amino group on the S-acyl cysteine residue. The mechanism for S - -N-dicy m ation has been disj ussed by Barnett and Jenks [145]. Patchornik et al. [8] noted that S- iV-acyl miration occurred when the free base of (60) was prepared and the low yields of S-benzoyl-L-cysteine peptides such as (61) were traced to the formation of (62), produced by S- -N-benzoyl migration during the coupling step [89, 146]. Similar difficulties have been noted in solid-phase synthesis [120]. Problems of this type may have also been encountered in the... 

Oxazaphospholidines of type 140 have been advocated as alternatives to the more normal phosphoramidite units used in solid-phase synthesis. The unit 141, as an isomeric mixture, has been developed as an all-purpose adaptor for synthesis of oligonucleotides on any of the commercial supports. The unit 141 is attached to the support through 0-5. After removal of the Dmtr group, the first nucleoside is attached via a 2 (3 )-3 link using a phosphoramidite. The desired oligonucleotide is then conventionally assembled, and disconnected by removal of the 0-benzoyl group from the adaptor, which is followed by cyclic phospho-diester formation. ... 

Besides acetyl, benzoyl, and benzyl protecting groups for the carbohydrate hydroxyl groups, silyl, isopropylidene, and p-methoxybcnzyl groups have also been employed in solid-phase glycopeptide synthesis. The synthesis of a glycopeptide... 

Figure 2.5 Solid Phase DNA Synthesis Cycle (Contd.). Most frequently used base protecting groups are shown Bz Af-6 benzoyl (adenine), W-4 benzoyl (cytosine) N-2 isobutyroyl (guanine). All are base sensitive. DNA chain is built up from 3 to 5 on controlled-pore glass (CPG) bead solid support. Post global deprotection and resin removal, the desired product oligo-/polydeoxynucleotide is then separated initially by precipitation by means of an agent such as ethanol and purified finally by reversed phase liquid chromatography, or ion exchange chromatography as appropriate (see later in Chapter 2).

Hammerstrom et al. [120] studied the synthesis of the B]. 3 sequence of insulin using the solid-phase technique. In these experiments ten different S-protective groups for the cysteine residue at B7 were evaluated including benzyl, p-methoxy-benzyl, benzhydryl, trityl, tetrahydropyranyl, benzylthio-methyl, ethylcarbamoyl, carbobenzyloxy, acetyl, and benzoyl. The benzyl, p-methoxybenzyl, benzhydryl, benzylthiomethyl, and ethylcarbamoyl withstood all synthetic operations but each, with the exception of the benzyl, was cleaved to a small extent when the peptide was removed from the resin with hydrogen bromide in trifluoroacetic acid. The S-tetrahydro-pyranyl was, on the other hand, cleanly removed by treatment with hydrogen bromide in trifluoroacetic acid and better overall... 

A new protecting group for 0-5 of nucleosides has been developed, particularly for use in solid phase oligonucleotide synthesis. This is the 2-(2,4-dinitrobenzenesulphenyloxymethyl)benzoyl (DNBSB) group (65), which is put on using the benzoic acid and pivaloyl... 

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