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. 2021 May 7:87:132117.
doi: 10.1016/j.tet.2021.132117. Epub 2021 Mar 29.

Total synthesis of (-)-4-desacetoxy-1-oxovindoline: Single atom exchange of an embedded core heteroatom in vindoline

Byron A Boon  1 , Yi-Yun Yu  1 , Dale L Boger  1
Affiliations

Total synthesis of (-)-4-desacetoxy-1-oxovindoline: Single atom exchange of an embedded core heteroatom in vindoline

Byron A Boon et al. Tetrahedron. .

Abstract

A concise total synthesis of (-)-4-desacetoxy-1-oxovindoline is disclosed, bearing a single heteroatom exchange in the core structure of the natural product 4-desacetoxyvindoline. Central to the synthesis is powerful oxadiazole intramolecular [4+2]/[3+2] cycloaddition cascade that formed four C-C bonds, created three new rings, and established five contiguous stereocenters about the new formed central 6-membered ring.

Keywords: Vinca alkaloids; oxadiazole cycloaddition cascade; vindoline analogue.

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Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could appear to influence the work reported in this paper.

Figures

Figure 1.
Figure 1.
Structure of natural products, target analogue 6, and key cycloaddition cascade.
Figure 2.
Figure 2.
Precedent for cycloaddition cascade [27].
Figure 3.
Figure 3.
Cascade cycloaddition optimization.
Figure 4.
Figure 4.
Chiral HPLC trace of racemic 21.
Scheme 1.
Scheme 1.
Synthesis of oxadiazole 18.
Scheme 2.
Scheme 2.
Completion of the synthesis of (–)-4-desacetoxy-1-oxovindoline (6).
See this image and copyright information in PMC

References

    1. The Alkaloids; Brossi A, Suffness M, Eds.; Academic: San Diego, 1990, Vol. 37.
    1. Neuss N, Barnes AJ Jr., Huckstep LL, Experientia 31 (1975) 18. - PubMed
    1. Barnett CJ, Cullinan GJ, Gerzon K, Hoying BC, Jones WE, Newlon WM, Poore GA, Robison RL, Sweeney MJ, Todd GC, Dyke RW, Nelson RL, Med RLJ. Chem 21 (1978) 88. - PubMed
    1. Lobert S, Vulevic B, Correia JJ, Biochemistry 35 (1996) 6806. - PubMed
    1. (a) Gout PW, Wijcik LL, Beer CT, Eur. J. Cancer 14 (1965) 1167. - PubMed
    2. (b) Ferguson PJ, Phillips JR, Selner M, Cass CE, Cancer Res 44 (1984) 3307. - PubMed

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