Details

Autor(en) / Beteiligte

• Kholod, Inga
• Vallat, Olivier
• Buciumas, Ana-Maria
• Neels, Antonia
• Neier, Reinhard

Titel

Synthetic Strategies for the Synthesis and Transformation of Substituted Pyrrolinones as Advanced Intermediates for Rhazinilam Analogues

Ist Teil von

• European journal of organic chemistry, 2014-12, Vol.2014 (35), p.7865-7877

Ort / Verlag

Weinheim: WILEY-VCH Verlag

Erscheinungsjahr

2014

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• The biaryl core structure of rhazinilam with its fixed dihedral angle is a pivotal element for its unique in vitro cytotoxic activity. Most of the related natural products are oxidized versions of rhazinilam. Replacing the sensitive pyrrole ring by a pyrrolinone ring is the basis of our initial strategy towards rhazinilam analogues. With this goal, variants of the sequence crossed Mukaiyama aldol reaction followed by the Staudinger reaction were studied. Reacting a suitably substituted acetophenone with O‐methyl O‐trimethylsilyl ketene acetal gave pyrrolinones 8a and 8b in good to excellent yields. These intermediates could be transformed in four high‐yielding steps into the pyrrolic precursors 7a–c containing all the atoms necessary for the construction of rings A, B, and C of rhazinilam. Our studies illustrate a lack of stability of these intermediates. Alternative synthetic approaches towards this central biaryl core structure are described. An efficient sequence that proceeds through the crossed Mukaiyama aldol reaction, Staudinger reaction, and hydroxy elimination has been developed for the syntheses of substituted 3‐pyrrolin‐2‐ones. This transformation has been used as a key step in the preparation of precursors containing all the atoms necessary for the construction of rings A, B, and C of rhazinilam analogues.