Mesembrine total synthesis

An effident total synthesis of the Scektium alkaloid (—)-mesembrine 112 has been accomplished in seven steps and 19% overall yield from the functionally substituted... 

Scheme 11.29. Total synthesis of the Sceletium alkaloid (—)-mesembrine 112 [75],...

Sceletium Alkaloids.—Another synthesis of ( )-mesembrine has been described,9 and also the first total synthesis of (—)-mesembranone (ll),10 summarized in Scheme 1. 

Chiral imidazolines such as 4, obtained by condensation of iminoether hydrochlorides with (15,25)-1,2-diaminocyclohexane, may be metalated and alkylated with high stereoselectivity. This process is highly efficient for the stereoselective synthesis of quaternary benzylic stereogenic centers, and has been applied to a total synthesis of mesembrine (eq 6). (15,25)-1,2-Diaminocyclohexane here again gives higher diastereomeric excesses than 1,2-diphenyl ethylenediamine in this reaction. 

The stereoselective total synthesis of ( )-elwesine (dihydrocrinine) (22 R = H, R = OH) has been previously reviewed details of this synthesis have now appeared. This report also presents i.r. and n.m.r. spectral evidence similar to that adduced by other workers which supports a rigid half-chair conformation with the bulky aryl group in an axial configuration for several synthetic mesembrine-like intermediates (23). Irradiation of the readily available )S-phenethylamine derivatives (24 R = OMe, R + R = OCH2O) and (24 R = H, R = OMe, R = OH) gave 2-methoxy-3-oxocrinine (25 R = OMe,... 

Rigby s studies on the synthesis of alkenylisocyanates fostered the preparation of a suitable substituted aryl enamide, which on photocyclization yielded the polysubstituted pentacyclic system. Key to the success of this process is the hydrogen bond between the phenolic OH and the carbonyl group, which restricts the rotation around the aryl-amide bond and directs the cyclization. Further functionalization allowed the total synthesis of pancratistatin (272) and narciclasine (68) (275) (Scheme 11). The [4-1-1] cycloaddition of bis(alkylthio)carbenes with vinyl isocyanates was the key process in a recent synthesis of (+)-mesembrine (92) 274). 

Utilizing a chiral, non-racemic amide, the reaction has been performed with high levels of diastereoselectivity, as demonstrated in the total synthesis of (+)-mesembrine." Birch reduction and alkylation produces 70 in > 99 1 dr. Hydrolysis and thermolysis results in the rearranged product 71 in good yield. The diminished yield in this example, as compared to above, is likely due to the competitive conjugation with aromatic ring in... 

J. B. P. A. Wijnberg and W. N. Speckamp. Total synthesis of d/-mesembrine, d/-dihydro-maritidine and d/-epidihydromaritidine via regioselective NaBH4/H+ reduction of imides. Tetrahedron, 1978,34,2579. 

Stevens, R. V. Lesko, P. M. Lapalme, R. General Methods of Alkaloid Synthesis. XI. Total Synthesis of the Sceletium Alkaloid A-4 and an Improved Synthesis of ( )-Mesembrine J. Orjf. Chem. 1975, 40, 3495-3498. 

Another example of the use of thiourea catalysts in total synthesis was reported by You and coworkers, who obtained (-)-mesembrine by means of an organocata-lyzed aza-Michael addition process (Scheme 44.8) [86]. The crucial step in this route is based on a previous study of the desymmetrization of cydohexadienones performed by the same research group [87]. On this occasion, the difficult task of controlling the sterically congested chiral arylated quaternary carbon center was... 

---