Melodinus alkaloids

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

Full details " have been published of the structural work on the Melodinus alkaloids. 

The formation of the tricyclic 9a-arylhydrolilolidine ring system is exemplified in the conversion of (154) to (155). Wolff ring contraction of the ketonic ring of (155) and further functional group modifications provided the Melodinus alkaloid ( )-meIoscine. (Scheme 55). 

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. 

In a further attempt to produce the Melodinus alkaloid skeleton, 320 was treated with 2 N sulfuric acid at 90-100° for 30 min (183). The product, obtained in 92% yield, was a quinolone, not of the Melodinus type but rather a 3-quinolone having the structure 337. Instead of the... 

Meloseine (3j8-H), I, g 1, 26 Epimeloscine (3a-H), CXXXIII, g 26 Meloscandine (3-formyl ), CXL, g 1, 26 Melodinus alkaloid 4 (3-carbomethoxy), CXXXIX, g26 Part 3. Meloseine Ci9H20N2O C19H20N2O C20H20N2O2 C21H22N2O3 group 188-190 Amorph. 1, 26 26 1, 26 26... 

The synthetic utility of the Overman pyrrolidine synthesis has been demonstrated in various approaches to a range of alkaloids the Amaryllidaceae alkaloids, Aspidosperma alkaloids, Strychnos alkaloids, and Melodinus alkaloids are several types. 

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],... 

Feldman et al. " and Oshima et al. have independently reported reactions of vinylcyclopropanes in the presence of olefins to obtain vinylcyclopentanes. Zhang and Curran used a divinylcyclopropane in a cascade radical annulation process, diastereoselectively generating three stereogenic centers (123 124) for the synthesis of Melodinus alkaloids epimeloscine and meloscine. This constitutes a new example of the synthetic value of radical chemistry in promoting a quick elaboration of complex polycyclic structures through cascade processes (Scheme 25.59). 

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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