Solid-phase synthesis of polynucleotides

Synthetic resins or natural rubbers -- part of the class 520 ser – Synthetic resins – Mixing of two or more solid polymers; mixing of solid...

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525340, 536 28, 536 29, 536 23, 536 24, C08F 840

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active

043730710

ABSTRACT:
A commercially available resin such as polystyrene is converted into a phthalimidomethyl-resin by treatment with potassium phthalimide. The phthalimidomethyl-resin is converted into an amino resin with hydrazine in ethanol. The amino resin is then combined with an activated ester of a nucleoside to obtain an amide-bonded dimethoxytrityl resin. The activated ester of the nucleoside is obtained by reacting a nucleoside with succinic anhydride in the presence of 4-(dimethylamino) pyridine in pyridine to provide a monosuccinate derivative, which is in turn treated with pentachlorophenol and dicyclohexylcarbodimide in dimethylformamide. Any unreacted amino groups in the amide-bonded dimethoxytrityl resin may be masked and the dimethoxytrityl group may be removed by treatment of the amide-bonded resin with a solution of benzenesulfonic acid to obtain a hydroxylated resin support. Additional mononucleotides, dinucleotides and trinucleotides may be added to the resin support in the presence of a coupling reagent such as 2,4,6-triisopropylbenzenesulfonyl tetrazolide. Any unreacted 5'-hydroxyl group may be masked with acetic anhydride. The steps described in the previous two sentences may be repeated to form polynucleotides of any desired sequence. The resin may also be a polyacrylmorpholide. This resin may be converted into an amino resin with ethylene diamine in ethylene glycol. The resin may also be a silica gel. The silica gel may be treated by any of the above methods, to provide a solid-phase resin support for the nucleotides.

REFERENCES:
patent: 3985690 (1976-10-01), Dean
patent: 4037037 (1977-07-01), Patchovnik et al.
patent: 4043948 (1977-08-01), Rayskys et al.
patent: 4066827 (1978-01-01), Seita
patent: 4217421 (1980-08-01), Beasley
patent: 4276395 (1981-06-01), Vollhardt et al.
Itakura et al., Tetrahedron Letters No. 38, pp. 3635-3638, 1979.

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