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Mechanistic studies on the phosphoramidite coupling reaction in oligonucleotide synthesis. I. Evidence for nudeophilic catalysis by tetrazole and rate variations with the phosphorus substituents

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Tetrazole catalyzed reactions of a series of phosphoramidites, 5′ -O- DMTdT-3′-O-P(OR 1)NRNR22 (1a-h), with 3′ O-SiBu tPh 2-6-N-benzoyl-dA (2a) in acetonitrite solution have been studied. It is found that the coupling rate depends very much on whether tetrazole is added before or after 2a, and that dialkylammonium tetrazolide salts are inhibitors. These and other facts are evidence that the reactions are subjected to nucleophilic catalysis by tetrazole, in addition to acid catalysis. The rate variations with phosphorus substituents of 1a-h are NEt 2 > NRr12 > N(CH 2CH 2)O > NMePh, and OMe > OCH 2CH 2CN > OCHMeCH 2CN > OCMe 2CH 2CN >> OC 6H 4Cl. The inhibitor properties of dialkylammonium tetrazolides have practical consequences for the efficiency of DNA syntheses, when in situ prepared phosphramidites are used; the same would apply for segmented simultaneous syntheses or syntheses where recycling is performed.

TidsskriftNucleic Acids Research
Udgave nummer4
Sider (fra-til)1729-1743
Antal sider15
StatusUdgivet - 25 feb. 1987

ID: 131115593