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. 2023 Aug 4;25(30):5553-5557.
doi: 10.1021/acs.orglett.3c01489. Epub 2023 Jun 30.

Cyclic Allene Approach to the Manzamine Alkaloid Keramaphidin B

Milauni M Mehta  1 , Jordan A M Gonzalez  1 , James L Bachman  1 , Neil K Garg  1
Affiliations

Cyclic Allene Approach to the Manzamine Alkaloid Keramaphidin B

Milauni M Mehta et al. Org Lett. .

Abstract

We report an approach to the core of the manzamine alkaloid keramaphidin B that relies on the strain-promoted cycloaddition of an azacyclic allene with a pyrone trapping partner. The cycloaddition is tolerant of nitrile and primary amide functional groups and can be complemented with a subsequent retro-Diels-Alder step. These efforts demonstrate that strained cyclic allenes can be used to build significant structural complexity and should encourage further studies of these fleeting intermediates.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1.
Figure 1.
(−)-Keramaphidin B (1), a complex manzamine alkaloid, and azacyclic allene 2, an underutilized synthetic building block.
Figure 2.
Figure 2.
Retrosynthetic analysis of (−)-keramaphidin B (1).
Figure 3.
Figure 3.
Model system for assembly of the azadecalin scaffold (14).
Figure 4.
Figure 4.
Synthesis of ImDA precursor 16 and evaluation of the intramolecular ImDA reaction.
Figure 5.
Figure 5.
Revised strategy to construct the [2.2.2]-azabicycle.
Figure 6.
Figure 6.
Synthesis of cyclic allene precursors 22a and 22b.
Figure 7.
Figure 7.
One-pot cycloaddition and CO2 extrusion to generate trienes 23a and 23b.
See this image and copyright information in PMC

References

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