21. Rohkamm R: Color Atlas of Neurology. George Thieme Verlag 2004.
Subsequently, the proposed transition-metal-catalyzed decarbonylation/electrocyclic ring-opening cascade reaction of 3 was attempted using several different catalysts (Rh, Ni, and Pd) in a variety of different solvents, as reported previously. However, these conditions failed to afford any of the desired product of 2. To our delight, the irradiation of a solution of β-lumicolchicine (3) in 10:1 (v/v) CH3CN/acetone (0.0024 mol/L) with a 125 W high-pressure mercury arc lamp surrounded by a Pyrex water jacket for 20 min gave 2 in 54% yield instead of α-lumicolchicine (4) and colchicine. The outcome of this transformation suggested that under the irradiation compound 3 had probably undergone a decarbonylation process to generate the intermediate B, followed by the anticipated retro-4π-electrocyclization reaction to give 2, which has been reported to exhibit greater inhibitory activity toward tubulin than colchicine. The 1H and 13C NMR spectra of synthetic 2 and 3, as well as their optical rotation, were identical to those of the natural products. We also have tried to extend the time of irradiation for one-pot synthesis of compound 2 from 1, but a trace of 2 was detected. Probably, other unidentified compounds made the reaction more complex, with the time extended and the temperature of the solution increased. So, after many attempts, we found that 25 min is the best time length for the first irradiation and the two-step sequence is more efficient than the one-pot procedure for the preparation of 2 from 1.
Georg Thieme Verlag; Stuttgart; 2012
Pharmaceutical Substances - Georg Thieme Verlag
Our synthesis began with the preparation of 6 (>99% ) from 5 in 5 steps in 21.8% overall yield, as reported previously (). The diastereoselective reduction of the ketone group in 6, followed by the chemoselective methylation of the resulting alcohol, afforded 8 in 75% yield (1.0 g scale). The structure of 8 was unambiguously confirmed using X-ray crystallography. After extensive experimentation, we found that the regioselective Wacker oxidation of the substituted olefin using air as a co-oxidant gave ketone 9 in good yield. We reasoned that the methoxy group at C10 in 8 was critical for this regioselective outcome. Finally, the double elimination of the oxa-bridge in 9 proceeded smoothly using a slightly modified version of Cha’s procedure in the presence of TMSOTf and Me2EtN in DCM to complete our total synthesis of (−)-1 in 81% yield in >99% . The 1H and 13C NMR spectra of synthetic 1, as well as its optical rotation, were identical to those of the natural product.
30/06/2017 · Georg Thieme Verlag KG ..
This three-stepsequence represents a useful tool for the efficient synthesisof diversely substituted
2-aminoimidazoles from readilyavailable starting materials.