Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• (DMTr) [26], tert-butyldimethylsilyl (TBDMS) [27][30], levulinoyl [26], or 2-azidomethylbenzoyl [27] (Figure 2), and applying either phosphotriester chemistry [28][29][31][32] or phosphite triester chemistry [25][26][27][30] in solution. In general, trinucleotides can be assembled through the reaction

• the applied conditions, can be efficiently cleaved, at the same time leaving all other protecting groups intact. Thus, a full set of all 20 trimers was synthesized by phosphotriester chemistry starting with the condensation of N-acyl-3'-O-(o-chlorophenylphosphate)nucleosides to 3'-O-(2

• proceed by either phosphite triester chemistry or phosphotriester chemistry with the latter being the more robust method. Also H-phosphonate chemistry has been used for assembling short oligomers in solution [34], although not with the aim of generating trinucleotide synthons for gene synthesis. 2

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• . While P(III)-based phosphoramidite and H-phosphonate chemistries are almost exclusively used on a solid support, the “outdated” P(V)-based phosphotriester chemistry still offers one major advantage for the synthesis on a soluble support; the omission of the oxidation step simplifies the coupling cycle

• phosphotriester chemistry The pioneering syntheses of ONs on a soluble support were carried out by the phosphotriester strategy. Although this coupling chemistry is seldom used on a solid support where small molecule reagents and wastes can be removed by simple washing, the avoidance of the oxidation step due to

• synthesis. Alternative coupling methods used in the synthesis of oligonucleotides. Synthesis of ODNs on a precipitative PEG-support by phosphotriester chemistry using MSNT/NMI activation [37]. Synthesis of ODNs on a precipitative tetrapodal support by phosphotriester chemistry using 1-hydroxybenzotriazole

Preparation of a disulfide-linked precipitative soluble support for solution-phase synthesis of trimeric oligodeoxyribonucleotide 3´-(2-chlorophenylphosphate) building blocks

• Amit M. Jabgunde,
• Alejandro Gimenez Molina,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2015, 11, 1553–1560, doi:10.3762/bjoc.11.171

• -protected oligodeoxyribonucleotide trimer 3’-pTpdCBzpdGibu-5’ as its 3’-(2-chlorophenyl phosphate) was achieved by reductive cleavage of the disulfide bond. Keywords: disulfide linker; oligodeoxyribonucleotides; phosphotriester chemistry; precipitation; soluble support; Introduction Synthetic nucleic

• -hydroxyethyldisulfanylmethyl)]-1H-1,2,3-triazol-1-ylmethyl]phenyl}pentaerythritol (3) has been synthesized and used as a tetrapodal soluble support for the synthesis of a fully protected trimeric oligodeoxyribonucleotide as a 3´-(2-chlorophenyl phosphate) by the 1-hydroxybenzotriazole promoted phosphotriester chemistry. The

Solution phase synthesis of short oligoribonucleotides on a precipitative tetrapodal support

• Alejandro Gimenez Molina,
• Amit M. Jabgunde,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2014, 10, 2279–2285, doi:10.3762/bjoc.10.237

• solution phase approach, allowing assembly of short RNAs in a hundreds of milligrams scale. While several such methods for the synthesis of DNA, based either the phosphoramidite [11][12][13][14][15][16], H-phosphonate [17][18][19] or phosphotriester chemistry [20][21][22], have been introduced, none of