Alkaloids, continued rearrangement

In fact, it isn t necessary to make 57 as, when R=Me, it is the natural alkaloid arecoline. However, when the synthesis was continued by attempted conjugate addition of the enolate of methyl acetoacetate to 57 only very low yields (12-18%) of products could be found. The problem turned out to be the base-catalysed rearrangement of 57 into the aromatic pyridone 71. 

The cyclopropylimine ynoline rearrangement (equation 68) has been exploited by Stevens in alkaloid syntheses. - Wenkert s cyclopropylcarbinyl rearrangement (equation 69) served extremely well in the design of 1,4-dicarbonyl synthons or 3,-y-unsaturated carbonyl compounds which then were expressed in numerous syntheses of terpenoid and alkaloid natural products. Donor-acceptor concepts continue to be express in the applicability of these rearrangements to organic synthesis. 

The Claisen rearrangement has been widely used in the synthesis of natural heterocyclic products. Although much of this work has been in the coumarin series, there are now several alkaloid syntheses in which the Claisen rearrangement features as a key step. Indications are that the Claisen rearrangement will continue to hold an important role in organic chemistry. 

A new application of the g.l.c. quantitative analysis method for tetramethylsilyl ethers of alkaloids has been reported. Mass spectrometric investigations of galanthamine and related compounds continue to interest Russian workers. The important technique of chemical ionization (C.I.) mass spectrometry has been applied to the Amaryllidaceae as well as many other alkaloid types. This method offers several advantages over the conventional electron impact (E.I.) mass spectrometric determination a quasi-molecular ion QM ) formed by protonation or hydride abstraction in ion-molecule collisions is always present aliphatic hydroxy- and methoxy-functions can always be determined and skeletal rearrangement is always absent. 

The continuing importance of mass spectrometric investigations in structural elucidation of alkaloids is evidenced by recent publications concerning biochemical applications, the study of stilbene-type methines of benzylisoquinoline alkaloids,the McLafferty rearrangement as exemplified by alkaloids, and an investigation of the mass spectral Hofmann elimination. ... 

Baldwin s rules on favoured and disfavoured ring closure reactions continue to generate interest. Pelletier and Mody provide an apparent example of a disfavoured 5trigonal ring closure (4) during rearrangement of the alkaloid... 

Alkaloids with polycyclic skdetal frameworks are, when it comes to their synthesis, excellent candidates for RCM. Illustrative are the indolizidines rhynchophylline (43) and its C(7)-epimer ixo-rhynchophylhne (44), both isolated from the plant Uncaria rhynchophytta (Rubiaceae) [26]. Deiters total synthesis of 43 and 44 started with the efficient construction of diallylamine 39 via amide formation between indole-3-acetic acid (38) and diallylamine (Scheme 2.10). One-pot RCM-carbomagnesation of 39 was smoothly achieved with only 1 mol% of [Ruj-I catalyst and 4 equiv. of EtMgCl to afford the 2-ethyl-3-butene-amine derivative in 71% yield. It appeared that the electron-withdrawing carbonyl moiety was critical to the success of the RCM-carbomagnesation steps. Amide reduction and subsequent treatment with acryloyl chloride dehvered the second metathesis precursor 40. Cyclization with [Ruj-I (5 mol%) then furnished the a,j8-unsaturated lactam 41 in a high yield of 91%. Continuation of the total synthesis of alkaloids 43 and 44 included a Bischler-Napieralski cychzation (42) and subsequent rearrangement into the oxindole framework. 

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