249287-96-5Relevant articles and documents
Use of the dithiasuccinoyl (Dts) amino protecting group for solid-phase synthesis of protected peptide nucleic acid (PNA) oligomers
Planas, Marta,Bardaji, Eduard,Jensen, Knud J.,Barany, George
, p. 7281 - 7289 (2007/10/03)
'Peptide nucleic acid' (PNA) oligomers replace the oligonucleotide backbone of DNA with an achiral and neutral poly[N-(2-aminoethyl)glycine] backbone, and the four natural nucleobases are attached through methylene carbonyl linkages to the glycine nitrogens. The present work describes the efficient conversion of N(ω)-Boc/side-chain Z-protected PNA monomers to the corresponding derivatives protected by the thiolyzable N(ω)-dithiasuccinoyl (Dts) function. After acidolytic removal of Boc, treatment with bis(ethoxythiocarbonyl) sulfide gave the N(ω)-ethoxythiocarbonyl (Etc) derivatives, which were silylated at the α-carboxyl and converted to the heterocycle by reaction with (chlorocarbonyl)sulfenyl chloride. Net yields of homogeneous monomers were 71-78%. Conditions in the solid-phase mode for thiolytic removal of the Dts group, and for coupling of protected monomers, have been studied extensively and optimized. A protocol featuring (i) Dts removal with dithiothreitol (DTT) (0.5 M) in acetic acid (HOAc) (0.5 M)- CH2Cl2 (2 + 8 min); (ii) short neutralization with N,N- diisopropylethylamine (DIEA)-CH2Cl2 (1:19, 1 + 2 min); and (iii) coupling mediated by HBTU-DIEA (3:1) in N-methyl-2-pyrrolidinone (NMP) (3 h) was applied to the solid-phase synthesis of Dts-T4-Gly-NH2, Dts-G(Z)-G(Z)-T- A(Z)-Gly-NH2, Dts-A(Z)-T-C(Z)-G(Z)-Gly-NH2, and Dts-G(Z)-C(Z)-A(Z)-T-Gly- NH2. The indicated protected PNA derivatives were released from the support, and their structures were verified by mass spectrometry.
