Phosphoramidites —

Oligonucleotide Synthesis (phosphoramidite method - Lessinger) Review Tetrahedron 1992, 48,2223... 

In step 1 of each oligonucleotide-synthesis cycle the 5 -terminal 4,4 -dimethoxytrityl protecting group is removed with trichloroacetic acid, and the support is washed with acetonitrile to prevent dctritylation of the next incoming phosphoramidite. The 4,4 -dimethoxy-... 

The protected nucleoside-3-phosphoramidite monomer units such as 671 are used in the solid-phase oligonucleotide synthesis. In the 60mer synthesis, 104 allylic protective groups are removed in almost 100% overall yield by the single Pd-catalyze reaction with formic acid and BuNH2[432], N,(9-protection of uridine derivatives was carried out under pha.se-transfer conditions[433]. 

Suitable methods for linking a phosphoms—nitrogen bond to the ayiridine ring are the aminolysis of halogenated phosphoms compounds (2,280—282), the transamination of phosphoramines with excess a iridine (283), the reaction with phosphites (284) and phosphoramidites (285) which have a free OH group, or the reaction of phosphines with a iridines and carbon tetrachloride (286). 

Chirahty at the phosphoms is an unavoidable problem in all phosphorothioate syntheses. The phosphoramidite method produces a mixture of both the and the diastereomers having a small excess of the isomer (53). Although some progress has been made in the chiral synthesis of dinucleoside phosphorothioates, low yields have limited the utility of these approaches. The chiral center may be eliminated by replacing the other, nonbridging oxygen with sulfur. Avoidance of the chirahty problem is one reason for the interest in phosphorodithioates. 

Phosphate triesters (18) are iatermediates ia both the phosphotriester and phosphoramidite methods, and under appropriate conditions for deprotection of the bases and cleavage of the support, can be obtained directiy by usiag these approaches. The ethyl and isopropyl esters have been obtained directiy by usiag the phosphoramidite method because these are stable duting the normal deprotection procedure (62). By changing the oxidizing agent to Sg, both amidate and triester thiolates can be obtained. 

The a-anomeric form of a 2 -deoxyribose, which has the base inverted with respect to the natural P-anomeric form, can be synthesized by using the phosphoramidite method sugar modification renders the derivatives nuclease-resistant. These analogues form parallel duplexes with complementary RNA... 

The disadvantage of this method is that the dichloridites and monochloridites are sensitive to water and thus could not be used readily in automated oligonucleotide synthesis. This problem was overcome by Beaucage and Caruthers, who developed the phosphoramidite approach. In this method, derivatives of the form R 0P(NR2)2 react with one equivalent of an alcohol (catalyzed by species such as l//-tetrazole) to form diesters, R OP(OR")NR2, which usually are stable, easily handled solids. These phosphoroamidites are easily converted to phosphite triesters by reaction with a second alcohol (catalyzed by l//-tetrazole). Here, again, oxidation of the phosphite triester with aqueous iodine affords the phosphate triester. Over the years, numerous protective groups and amines have been examined for use in this approach. Much of the work has been reviewed. ... 

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. " ... 

These groups, along with a number of other trialkylsilylethyl derivatives, were examined for protection of phosphorothioates. Only the phenyl-substituted silyl derivative was useful, because simple trialkylsilyl derivatives were prone to acid-catalyzed thiono-thiolo rearrangement. Other trialkylsilylethyl derivatives also suffer from inherent instability upon storage,but the trimethylsilylethyl group has been used successfully in the synthesis of the very sensitive agrocin 84 and for intemucleotide phosphate protection with the phosphoramidite approach. 

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

Phosphine(s), chirality of, 314 Phosphite, DNA synthesis and, 1115 oxidation of, 1116 Phospholipid, 1066-1067 classification of, 1066 Phosphopantetheine, coenzyme A from. 817 structure of, 1127 Phosphoramidite, DNA synthesis and, 1115 Phosphoranc, 720 Phosphoric acid, pKa of, 51 Phosphoric acid anhydride, 1127 Phosphorus, hybridization of, 20 Phosphorus oxychloride, alcohol dehydration with. 620-622 Phosphorus tribromide, reaction with alcohols. 344. 618 Photochemical reaction, 1181 Photolithography, 505-506 resists for, 505-506 Photon, 419 energy- of. 420 Photosynthesis, 973-974 Phthalic acid, structure of, 753 Phthalimide, Gabriel amine synthesis and, 929... 

Pineschi and Feringa reported that chiral copper phosphoramidite catalysts mediate a regiodivergent kinetic resolution (RKR) of cyclic unsaturated epoxides with dialkylzinc reagents, in which epoxide enantiomers are selectively transformed into different regioisomers (allylic and homoallylic alcohols) [90]. The method was also applied to both s-cis and s-trans cyclic allylic epoxides (Schemes 7.45 and 7.46,... 

Phi = NTs ([N-(p-toluenesulfonyl)iminio]phe-nyliodinane) 79 phomactin A 307 (+)-phonomactin 277 ( )-phoracantholide 299 phosphazene base 3 f. phosphazine base 31 phospholene epoxide 243 phosphoramidite 261 phosphoramidite ligand 247 piperidinephosphonate 103 pipermethystine 302 P K 177... 

Dialkyl dimethyl phosphoramidites (16) react with j8-propiolactone to give the phosphoramidate (17) and the phosphonate (18), A kinetic study suggests a mechanism involving initial attack of phosphorus at saturated carbon to give (17), while a four-centred transition state (19) is invoked to explain the formation of (18). 

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