Phosphate protecting groups

DBU, CH3CN, 140 s. The 2-(4-nitrophenyl)ethyl (Npe) phosphate protective group and the 2-(4-nitrophenyl)ethoxycarbonyl (Npeoc) group are stable to these conditions, but the cyanoethyl group is not. 

The following sections primarily describe many of the methods used for the cleavage of some of the more common phosphate protective groups. Since most of these groups are introduced by either the phosphate or phosphite method, little information is included here about their formation. The cited references generally describe the means that were used to introduce the protective group. In some cases, methods of formation are described, but this is done only when alternative methods to the phosphate or phosphite procedure were used. 

This easily prepared lipophilic 5 -phosphate protective group is cleaved by NCS oxidation (dioxane, triethylammonium hydrogen carbonate, 2 h, rt) followed by ammonia-induced j3-elimination. ... 

The lipophilicity of this phosphate protective group helps in the chromatographic purification of oligonucleotides. It is removed by the oximate method. ... 

This highly lipophilic group is cleaved with isoamyl nitrite in Pyr/AcOH. The use of a lipophilic 5 -phosphate protective group aids in reverse-phase HPLC purification of oligonucleotides. 

Example 40 mononucleoside phosphotriester derivatives with 5-acyl-2-thioethyl bioreversible phosphate-protecting groups have been synthesized by Imbach and his associates [74a,b] in their research on intracellular delivery of 3 -azido-3 -dideoxythymidine-5 -mono-phosphate. 

The enzymes used to generate reactive quinone methides often undergo inactivation by addition of this electrophile to essential nucleophilic amino acid side chains of the protein catalyst. This is a type of suicide enzyme inhibition.80 This was observed for the acid phosphatase and ribonuclease catalysts used to generate 43.76 79 Alkaline phosphatase has been used to remove the phosphate protecting group from a derivative of an o-difluoromethyl phenyl phosphate that was covalently attached to a solid support. Breakdown of the immobilized 4-hydroxybenzyl difluoride gives an immobilized quinone methide that, in principle, will react irreversibly with proteins and lead to their attachment to the solid support.81... 

Rubinstein, M., Amit, B. and Patchornik, A. (1975) Use of a light-sensitive phosphate protecting group for mononucleotide syntheses. Tetrahedron Letters, 16, 1445-1448. 

Introduction of a phosphate monoester and removal of its protecting groups was a serious impediment in a synthesis of the serine-threonine phosphatase inhibitor Calyculin A by Evans and co-workers [Scheme 7,22].38 The four phosphate protecting groups evaluated were 2-cyanoethyl and 2-(trimethylsi]y])ethyl (see below), benzyl and p-methoxybenzyl. Of these, the p-methoxybenzyl phosphate ester offered the best compromise between base stability (it survived a Wittig reaction in the presence of a metal amide base) and acid lability required for the final deprotection step in which three secondary terf-butyldimethylsiiyl... 

The 2-(methylsulfonyl)ethyl group 5 together with its fert-butyl-,86 phenyl-87 and benzyl-substituted88 relatives, comprise a small group of phosphate protecting groups that cleave with mild bases such as triethylamine. The van Boom... 

---