Asymmetric synthesis of the allocolchicinoid natural product N-acetylcolchinol methyl ether (suhailamine), solid state and solution phase conformational analysis

Journal article

An asymmetric synthesis of the allocolchicinoid N-acetylcolchinol methyl ether (NCME) from 3-methoxybenzaldehyde is reported. Comparison of 1H and 13C NMR spectroscopic data obtained for this sample of NCME provide further evidence for the assertion that this compound is congruous with the natural product that has been dubbed suhailamine, establishing NCME as a naturally-occurring allocolchicinoid. The single crystal X-ray diffraction structure of NCME is also reported for the first time, revealing a preference for adoption of the (7S,Ra,Z) form—i.e., describing the orientation of the biaryl axis and the amide N–CO bond as well as the configuration of the stereocenic centre—in the solid state. A preference for the same form in DMSO-d6 solution is revealed upon analysis by a range of NMR spectroscopic techniques, whilst an interconverting 69:24:7 mixture of the (7S,Ra,Z), (7S,Sa,Z) and (7S,Ra,E) forms is observed in CDCl3.

Authors: Davies, S; Fletcher, A; Roberts, P; Thomson, J; Yeung, A

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Tetrahedron
• Volume: 75
• Issue: 49
• Article number: 130694
• Publication date: 2019-10-18
• Acceptance date: 2019-10-14
• DOI: 10.1016/j.tet.2019.130694
• EISSN: 1464-5416
• ISSN: 0040-4020
• Language: English
• Keywords: FFR