Meloscine total synthesis

Selig, P. and Bach, T. (2008) Enantioselective total synthesis of the melodinus alkaloid (+ )-meloscine. Angewandte Chemie, International Edition, 47, 5082-5084. 

The stereocontrolled total synthesis of the structurally unusual pentacyclic Melodinus alkaloid ( )-meloscine (29a) and ( )-epimeloscine (29b) was achieved starting from the aza-Cope precursor 231139. 

As in the case of all variations of the Clasien rearrangement, the [3,3]-sigmatropic process is routinely applied for the construction of stereogenicity at quaternary carbon centers. During studies toward the total synthesis of meloscine, orthoester Johnson-Claisen rearrangement was utilized as the key bond formation event when many other attempts to construct the C5 quaternary stereocenter in this sterically-demanding environment failed. Treatment of 351 with trimethyl orthoacetate at elevated temperature readily afforded the ester 352 with moderate diastereoselection." ... 

Mukai and coworkers reported the concise total synthesis of Melodinus alkaloid ( )-meloscine (40) [Route (a), Fig. 13], in which the final key transformation involved an alkene RCM of the triene precursor (42) in the presence of Hoveyda-Grubbs II catalyst [55], The RCM between the A(-allyl group and the top-oriented vinyl moiety exclusively occurred to generate the desired diastereomer (40) in almost quantitative yield. The extremely high diastereoselectivity could be rationalized on the basis of ring strain to favor one conformer. Shortly after this work, Curran et al. disclosed another approach to the total syntheses of ( )-epimeloscine (41) and ( )-meloscine (40) applying the same RCM protocol for the final ring formation [Route (b), Fig. 13] [56],... 

Zhang H, Curran DP. A short total synthesis of ( )-epimeloscine and ( )-meloscine enabled by a cascade radical annulation of a divinylcyclopropane. J. Am. Chem. Soc. 2011 133(27) 10376-10378. 

Total Synthesis of Meloscine Meloscine 189, a member of the Melodinus alkaloids group, is noted for containing a six-membered quinolone ring within a mono-terpenoid Aspidosperma carbon skeleton. 

Although the Melodinus alkaloids do not possess useful biological activity for humans, synthetic organic chemists are attracted to their unique structural features. Bach and co-workers reported on a total synthesis of meloscine by employing a three-step reductive amination domino sequence among the total 15 steps to synthesize the racemic target molecule in 9% overall yield (Scheme 39.54). 

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