0 Hits

  • Previous / Next

You are using Science Of Synthesis as a Guest.
Please login to access the full content or check if you have access via Wittig-Based Macrocyclization in DNA-Templated Libraries

DOI: 10.1055/sos-SD-241-00235

Gillingham, D.; Sauter, B.Science of Synthesis: DNA-Encoded Libraries, (20241562.

An early example of macrocyclization in DNA-encoded chemistry is found in the pioneering DNA-templated synthesis work of the Liu group.[‌6‌‌8‌] They built a series of DNA-linked reagents that could then be selectively reacted with a growing small molecule attached to the end of a template DNA. In the penultimate step of their synthesis, they introduced (through amide coupling) a small library of phosphonium salts capable of producing stabilized phosphorus ylides at high pH. By oxidatively cleaving a diol on the other end of the molecule with periodate and then raising the pH, they initiated an intramolecular Wittig reaction to form the macrocycle.[‌6‌] Although, in general, the DNA-templated library design used by the Liu group has been superseded by the DNA-recorded chemistry championed by Praecis[‌9‌] and the ETH DEL lab,[‌10‌,‌11‌] it is strange that Wittig chemistry has not since been used in DEL synthesis, as the reaction is highly efficient, delivering 60–90% yield across 11 individual substrates tested.

Meeeee 8 Meeeee-Meeee Meeeeeeeeeeeeeee[‌8‌,‌8‌]

Meeeeeeeeeee Meeeeeeee

Meeeee-Meeee Meeeeeeeeeeeeeee (Meeeee 8); Meeeeee Meeeeeeee:[‌8‌,‌8‌]

Mee eeeeeee eee eeeeeeeeeee ee eeeeeeeeeeee eeeeeeee eeeee eee eeee eeeeeee eeee 88 eM MeMM8 ee 888 eM ee MeMMe (eM 8.8) eee 8 eee ee eeeeeeeeeee eeeeee eee eeee ee eeeee eee eeeeeeeeeeee. Mee eeeee eeee eeee eeeeee eeee eeee 888 eM ee MeMMe (eM 8.8) eee eeee eeee 88 eM ee MeMMe (eM 8.8) ee eeeeee eeeeeeee eeeeeeeee. Meeeeeeeeee eee eeee eeeeeee ee eeeeeeeeeeee eee eeeee ee 8.8 M ee MMMMM (eM 8.8) eeee 8 M ee MeMe eee eeeeeeeee eee 8 e. Mee Meeeee eeeeeeee eeeeeeee eee eeeee eeeeeee eeee eee eeeeee-eeeeee eeeeeeeeeeeeeee, eee eeeee, eee eeeeeee eeeeeee eee eeeeeeeee ee eee eeeeeeeeeee ee eeee ee ee eeee eeeeee ee eee eeeee eeee M8M.