Applications aspidosperma alkaloids

The intramolecular cycloaddition reaction of enamides has been exploited in alkaloid synthesis (81JOC3763). One successful application is provided by the total synthesis of the fused indolizidine 5 from 4 as a 1 1 mixture of epimers in 43% total yield 5 is a key intermediate in aspidosperma alkaloid synthesis (79JA3294). 

In more recent work, Chiu and co-workers [167, 168] have reported an intramolecular 1,3-dipolar cycloaddition approach toward the pseudolaric acids 85, in which the di-polarophile is an unactivated 1,1-disubstituted alkene. Hence, treatment of the diazo ketone 86 with catalytic Rh2(OAc)4 furnished a mixture of tricyclic products 87 and 88 in nearly equal proportions (Scheme 19.13). The synthesis of 2-pyridones [169] and their application to the ipalbidine core [170] has been described. The pentacyclic skeleton of the aspidosperma alkaloids was prepared via the cycloaddition of a push-pull carbonyl ylide [171]. The dehydrovindorosine alkaloids 89 have also been investigated, in which the a-diazo-/ -ketoester 90 undergoes a facile cycloaddition to furnish 91 in... 

The A2-piperideines are capable of behaving as dehydrosecodine analogs in alkaloid synthesis. One of the first successful applications of this approach is provided by the total synthesis of the aspidosperma alkaloid minovine (234 Scheme 41) (73JA7146). 

Magnus and his group have discovered a new method of cyclization via quinodimethane intermediates, which avoids the problems associated with the well known methods involving benzocyclobutenes, dihydrothiophen dioxides, etc. The discovery was made after the observation that when the trimethylsilyl derivative (173) was treated with fluoride ion cyclization did not occur, only (174) was isolated. The cyclization to (175) is affected in good yield by heating (174) with acetic anhydride, and although the method is being developed for synthesis of Aspidosperma alkaloids, it promises to have much wider application. 

Scheme 3.44 Application of the piperidine synthesis developed by Ghosez to the preparation of a precursor to Aspidosperma alkaloids.

CP-MAS has allowed the study of conformations and cross-linkages in natural and synthetic polymers, and of structures of proteins, nucleic acids, phospholipid membranes, etc. The field is still in its infancy and its applications will undoubtedly grow. The CP-MAS solid state C-NMR spectrum of 19S-vindolinine, has been studied by Atta-ur-Rahman and coworkers at H.E.J. Research Institute of Chemistry, and it is shown in Figure 4.16. It represents the first example of a CP-MAS spectrum of a solid Aspidosperma alkaloid ever recorded. 

Padwa extensively studied a collection of innovative applications of [l,3]-di-polar cycloadditions involving carbonyl ylides [58]. The sequence in which 38 is converted into the aspidosperma alkaloid 40 serves as a striking example (Scheme 18.10) [60]. Treatment of the diazoketone 38 with Rh2(OAc)4 leads to the formation of a putative ylide 39, which captures the electron-rich... 

The study of Fuji et al. shows that the addition of lithium enolate 75 to ni-troamine 74 is readily reversible quenching conditions are thus essential for getting a good yield of product 76. An equilibrium mixture of the adducts exists in the reaction mixture, and the elimination of either the prolinol or lactone moiety can take place depending on the workup condition (Scheme 2-34). A feature of this asymmetric synthesis is the direct one pot formation of the enantiomer with a high ee value. One application of this reaction is the asymmetric synthesis of a key intermediate for indole type Aspidosperma and Hun-teria alkaloids.68 Fuji69 has reviewed the asymmetric creation of quaternary carbon atoms. 

Schnoes H K, Burlingame A L, Biemann K 1962 Application of mass spectrometry to structure problems. The occurrence of eburnamenine and related alkaloids in Rhazya stricta and Aspidosperma quebracho bianco. Tetrahedron Lett 993 - 999... 

Biemann K, Spiteller-Friedmann M, Spiteller G. Application of mass spectrometry to stmcture problems. X. Alkaloids of the bark of Aspidosperma quebracho bianco. J. Am. Chem. Soc. 1963 85(5) 631-638. 

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