Nucleoside phosphites

Polynucleotides. These compounds are now generally prepared by use of a bifunctional phosphitylating agent such as o-chlorophenylphosphorodichloridite (6, 114-115) or methoxydichlorophosphine, CHjOPCl,. The intermediate nucleoside phosphites from these reagents tend to be unstable. This difficulty can be alleviated by use of I, which reacts with suitably protected nucleosides to form stable phosphoramidales 2 in good yield. These products can be activated for formation of a dinucleotide phosphite (4) by treatment with a weak acid such as N,N-dimethylaniline hydrochloride or l/Z-tetrazole (5). 

Bis(trimethylsilyl) peroxide, (CH3)3SiOOSi(CH3)3, is prepared from trimethylsilyl chloride, l,4-diaza[2,2,2]bicyclooctane, and Dabco s complex with 2 mol of hydrogen peroxide [127]. It is used alone [228] or in the presence of catalysts such as pyridinium dichromate [236] trimethylsilyl trifluoromethanesulfonate, CF3S03Si(CH3)3 [228, 237] or tris-(triphenylphosphine)ruthenium dichloride, [(C6H5)3P]3RuCl2 [236]. This reagent oxidizes primary alcohols to aldehydes (in preference to the oxidation of secondary alcohols to ketones [236]), ketones to esters or lactones Baeyer-Villiger reaction) [238], and nucleoside phosphites to phosphates [228]. All these oxidations require anhydrous conditions. 

The oxidation of phosphites to phosphates is very important in the chemistry of nucleoside phosphites, which must be handled under anhydrous conditions. For this purpose, anhydrous hydrogen peroxide bis(trimethylsilyl) peroxide, cumene hydroperoxide, and iV-methylmor ... 

Nucleoside phosphites. Reaction of a nucleoside with phosphorous acid and di-p-tolylcarbodiimide in pyridine affords the nucleoside phosphite in good yield." Thus... 

Polynucleoside Phosphate Derivatives. A convenient method for the oxidation of nucleoside phosphite triesters into phosphate triesters under non-basic and non-aqueous conditions using commercially available ethyl(methyl)diox-irane has been reported (Scheme 5). ° This oxidation method could be used with both N-protected and iV-unprotected nucleosides (80a-m), and was efficiently applied to nucleotide synthesis both in solution phase and on solid support. 

In these systems, the nucleoside phosphite formed is then oxidized (reagent, in italics) to nucleoside phosphates. 

Tris(hexafluoroisopropyl) phosphite (105) has been used to prepare ribonucleoside H-phosphonates (106), and deoxyribo-nucleoside phosphites (107) ° both were used as monomers to prepare oligonucleoside H-phosphonates on a solid support, with W-methylimidazole as catalyst for the coupling of (107). Several new alkyl phosphorodiamidites (108) and (109) have been used... 

A series of 3 -phosphoreonidite derivatives of 2 -deoxyribo-nucleosides protected at 0-5 have been synthesized in connection with oligonucleotide synthesis,and the non-aqueous oxidation of nucleoside phosphites to phosphates has been studied, with bis-... 

G>mplexes such as 193, between nucleoside phosphites and tungstm t cacaibonyl have been characterized. ... 

Hayakawa, Y, Uchiyama, M, and Noyori, R. (1986) Nonaqueous oxidation of nucleoside phosphites to the phosphates. Tetrahedron Lett, 27,4191-4194... 

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