Four New DNA Building Blocks DNA Nucleotides

Home , DNA, RNA

S. HOSHIKA, N. A. LEAL, M.-J. KIM, M.-S. KIM, N. B. KARALKAR, H.-J. KIM, A. M. BATES, Category N. E. J. WATKINS, H. A. SANTALUCIA, A. J. MEYER, S. DASGUPTA, J. A. PICCIRILLI, A. Chemistry in D. ELLINGTON, J. J. SANTALUCIA, M. M. GEORGIADIS, S. A. BENNER* (FIREBIRD Medicine and BIOMOLECULAR SCIENCES LLC AND FOUNDATION FOR APPLIED MOLECULAR EVOLUTION, Biology ALACHUA, INDIANA UNIVERSITY SCHOOL OF MEDICINE, UNIVERSITY OF CHICAGO UNIVERSITY OF TEXAS, AUSTIN, AND DNA SOFTWARE INC., ANN ARBOR, USA) Hachimoji DNA and RNA: A Genetic System with Eight Building Blocks Key words Science 2019, 363, 884–887. RNA Four New DNA Building Blocks DNA nucleotides

Hachimoji DNA H H H N H O N O2N N H O N N N H N N H N N dR dR N N N O H N dR dR O H N H H dC dG dZ dP H H Me O H N Me O H N N N N N N H N N N H N dR dR N N N N H O dR O dR H dT dA dS dB

Representative synthesis of dS phosphoramidite: O O Me Me O NNH NNH 1. Pd(OAc)2, Ph3As HO O Me N NH Bu3N, DMF TBS-Cl + O O 93% yield OTBDPS O 2. TBAF, HOAc HO O TBSO O I 3. NaBH(OAc)3, HOAc

51% over three steps OH OTBS O O Me Me NN NN 1. BzCl, py 1. A, DMAP NH2 2. Et N⋅HF NHBz 3 TBSO 3. DMTr-Cl, py 2. aq NH3 O DMTrO O 75% over two steps 4. B, DIPEA 33% over three steps OTBS O O NC P i-Pr O A Cl O Cl N S NC P O N This document was downloaded for personal use only. Unauthorized distribution is strictly prohibited. i-Pr i-Pr B DMTr = 4,4'-dimethoxytrityl

Significance: An artificial genetic system, hachi- Comment: The synthesis of hachimoji DNA in- moji DNA (from Japanese ‘eight letters’) has been volves the novel purines P and B and the pyrimi- obtained using novel nucleotides P, B, Z, and S in dines Z and S analogues. The representative syn- combination with standard nucleotides. Hachimoji thesis of dS phosphoramidite was reported DNA builds structures with properties similar to previously by Benner and co-workers in Bioorg. those of natural DNA and can be transcribed into Med. Chem. 2009, 17, 3728. hachimoji RNA.

SYNFACTS Contributors: Dirk Trauner, Andrej Shemet Synfacts 02052019, 15(05), 0555 Published online: 15.04.20191861-19581861-194X