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. 2013 Jan 9;135(1):519-28.
doi: 10.1021/ja3111626. Epub 2012 Dec 26.

Access to the akuammiline family of alkaloids: total synthesis of (+)-scholarisine A

Gregory L Adams  1 , Patrick J Carroll, Amos B Smith 3rd
Affiliations

Access to the akuammiline family of alkaloids: total synthesis of (+)-scholarisine A

Gregory L Adams et al. J Am Chem Soc. .

Abstract

The planning and implementation of an enantioselective total synthesis of (+)-scholarisine A is presented. Key tactics employed include a novel cyclization, consisting of a nitrile reduction coupled with concomitant addition of the resultant amine to an epoxide; a modified Fischer indolization; an oxidative lactonization of a diol in the presence of an indole ring; and a late-stage cyclization to complete the caged ring scaffold. The development of a possible "retro-biosynthetic" approach to other members of the akuammiline alkaloid family is also described.

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Figures

Figure 1
Figure 1
Representative Akuammiline Alkaloids.
Figure 2
Figure 2
Open Form View of Akuammiline Alkaloids.
Figure 3
Figure 3
Fragmentation Approach to the Akuammiline Core.
Figure 4
Figure 4
Initial Retrosynthetic Analysis.
Figure 5
Figure 5
A NOE Derived Model of the Reactivity of (+)-61
Figure 6
Figure 6
A New Plan Forward.
Scheme 1
Scheme 1
Synthesis of Lactone (−)-32
Scheme 2
Scheme 2
Synthesis of Epoxide (−)-33
Scheme 3
Scheme 3
Synthesis of Ketone (+)-44
Scheme 4
Scheme 4
Synthesis of Ketone (+)-45
Scheme 5
Scheme 5
Initial Indole Synthesis
Scheme 6
Scheme 6
Synthesis of Indole (−)-49
Scheme 7
Scheme 7
Synthesis of Indole (−)-52
Scheme 8
Scheme 8
Lactone Opening and Hydroxyl Protection
Scheme 9
Scheme 9
Synthesis of Aldehyde (+)-56
Scheme 10
Scheme 10
Synthesis of Diol (+)-62
Scheme 11
Scheme 11
Initial Oxidative-Lactonization
Scheme 12
Scheme 12
Two Step Oxidative-Lactonization
Scheme 13
Scheme 13
Total Synthesis of (+)-Scholarisine A (1)
Scheme 14
Scheme 14
A “Retrobiosynthetic” Fragmentation
See this image and copyright information in PMC

References

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