Removal of Protective Groups from Phosphorus

All the approaches for deblocking of protective groups described earlier in this book have found application in the removal of protective groups from phosphorus derivatives. Because phosphate protection and deprotection is commonly associated with compounds that contain acid-sensitive sites (e.g., glycosidic linkages and DMTr—O 

Groups removed by base (in one step, or the second of two steps). 

Photolysis P —O-R — 3,5-dinitrophenyl, 2-nitrobenzyl, 3,5-dimethoxybenzyl, pyrenylmethyl, desyl, 4-methoxybenzoylmethyl 

The following section primarily describes 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, hut this is done only when alternative methods to the phosphate or phosphite procedure were used. 

Ohtsuka, H. Tsuji, T. Miyake, and M. Ikehara, Chem. Pharm. Bull., 25, 2844 (1977). 

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SOME GENERAL METHODS FOR PHOSPHATE ESTER FORMATION REMOVAL OF PROTECTIVE GROUPS FROM PHOSPHORUS... 

O-isopropylidene derivative (10) was then phosphorylated with phosphorous oxychloride to form the phosphate ester (11) from which the protecting groups were removed by mild acid hydrolysis. The 3-phos-phate (15) was obtained by phosphorylating the 4,6-benzylidene derivative (13) of the same glycoside with phosphorus oxychloride, followed by hydrolytic removal of the protecting groups, from the ester (14) thus obtained. 

The combination of triphenylphosphine with esters of trihaloacetic acids provides a reagent system for the stereo- and regio-selective conversion of alcohols into alkyl halides.The bromine-triphenylphosphine adduct has been used at low temperatures (-50 C in dichloromethane) for the removal of the tetrahydropyranyl protecting group from tetrahydropyranyl ethers derived from secondary and tertiary alcohols.The reactions of tertiary phosphines (and other trivalent phosphorus compounds) with iodine in aprotic solvents have received further study, a range of species being identified.The first reported study of the reactions of trivalent phosphorus compounds with monopositive astatine has led to the identification of stable complexes with triphenylphosphine, trioctylphosphine, and triethylphosphite. 

A new method for the preparation of 5 -amino-5 -deox)mucleotides has been described, based on the reaction between phosphorus triesters and phenyl azide. Treatment of protected 5 -azido-5 -deoxynucleosides with trimethyl or triphenyl phosphite leads, after removal of the nucleoside protecting groups and one of the esterifying groups from the phosphoryl residue, to the phosphoramidates (9). Snake venom phosphodiesterase hydrolyses (9) to 5 -aminonucleosides. 

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