Phosphoramidites phosphorylation

The cyclohexyl phosphate, used in the protection of phosphorylated serine derivatives, is introduced by the phosphoramidite method and cleaved with TFMSA/MTB/m-cresol/l,2-ethanedithiol/TFA, 4 h, 0° to rt. " ... 

The phosphate ester, prepared either through phosphoramidite or phosphoryl chloride protocols, is cleavable by photolysis (350 nm, benzene, 83-87% yield)." ... 

It was later found that dialkyl(dialkylamino) phosphites (phosphoramidites, (RO)2PNR2 [114]), which are stable towards air and water and can be stored for longer, can readily be converted into the phosphinic chlorides (RO)2PCl by treatment with dimethylaniline hydrochloride, or into the corresponding tetrazolides by treatment with tetrazole. Tetrazolides (RO)2P-(l-tetrazolyl) had proven excellent reagents for the phosphorylation of nucleosides [113], and the treatment of phosphoramidites with alcohols in the presence of tetrazole was found to be a satisfactory method for the rapid preparation of trialkyl phosphites [115,116]. 

Glycosyl phosphates are important building blocks in carbohydrate synthesis. Hindsgaul and co-workers18 applied a capture-phosphorylation method with a polystyrene-supported phosphoramidite to simplify their synthesis (entry 14). Unreacted alcohols are removed by washing the resin and the desired glcyophosphates are released in high purity by a standard... 

Key Words Global phosphorylation phosphopeptide phosphoramidite phosphoserine phosphothreonine phosphotyrosine. 

The key [4+2] glycosylation followed by desilylation of the two phosphorylation sites resulted in a moderate 39% yield over two steps (Scheme 13.23). Phosphoramidite 153 was used to phosphorylate both of the resulting free hydroxy groups. A three-step protocol was applied for final deprotection, starting with azide reduction with Zn and acetic acid, then removal of cyanoethoxy phosphate protection with DBU, and finally... 

The Synthesis of Specific Ribonucleotides and Unrelated Phosphorylated Biomolecules by the Phosphoramidite Method, Beaucage, S. L. Iyer, R. P Tetrahedron 1993, 49, 10441-10488. 

Givens58 and Pirrung59 used photolabile 3 3 -dimethoxybenzoin esters for the protection of phosphotriesters. A complication attending the use of racemic 3 5 dimethoxybenzoin is the generation of four diastereoisomers if the phosphate is chiral. An asymmetric synthesis of 3, 5 -dimethoxybenzoin 303 [Scheme 7.30] via the 0-trimethylsilyl-3,5-dimethoxybenzaldehyde cyanohydrin 303 minimises the number of diastereoisomers created in the phosphorylation of chiral alcohols. Thus reaction of 303 with 2 - cyanoethoxy)(NPNf-diisopropy amino)-chlorophosphine afforded the phosphoramidite 30.4 which then reacted with Boc-Ser-OMe to give the two diastereoisomeric phosphotriesters 303, Photode-... 

Figure 6.7. Solid-Phase Synthesis of a DNA Chain by the Phosphite Triester Method. The activated monomer added to the growing chain is a deoxyribonucleoside 3 -phosphoramidite containing a DMT protecting group on its 5 oxygen atom, a p -cyanoethyl ( p CE) protecting group on its 3 phosphoryl oxygen, and a protecting group on the base.

The synthesis and incorporation into oligonucleotides of the A-phosphory-lated deoxycytidine 3 -phosphoramidites (144) and (145) obtained either from the O-protected 2 -deoxycytidine and bis(2-cyanoethyl) A,A-diisopropyl phosphoramidite or diethylphosphorochloridite, respectively, was described by Sekine. Sekine also reported that the A-phosphorylated derivatives of 2 -deoxy adenosine decomposed readily and were unsuitable for incorporation into oligodeoxynucleotides. 

The single reported synthesis of D-(l-IPj ) started from L-quebrachitol. The main problems were the stereospecific inversion of one OH group and the demethylation from oxygen. Phosphorylation of a benzylated intermediate was achieved using the cyclic phosphoramidite (7) as phosphitylating agent with subsequent... 

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