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. 2007 Jul 20;72(15):5784-93.
doi: 10.1021/jo070901r. Epub 2007 Jun 27.

Total synthesis of leucascandrolide a: a new application of the Mukaiyama aldol-Prins reaction

Lori J Van Orden  1 , Brian D Patterson, Scott D Rychnovsky
Affiliations

Total synthesis of leucascandrolide a: a new application of the Mukaiyama aldol-Prins reaction

Lori J Van Orden et al. J Org Chem. .

Abstract

A total synthesis of the marine natural product leucascandrolide A has been completed. The titanium tetrabromide-mediated Mukaiyama aldol-Prins (MAP) reaction with aldehydes developed in our group provided a highly convergent and stereoselective method for assembling the core of the molecule. A new class of MAP reactions with acetals is introduced, and mechanistic considerations for both MAP methods are described. The total synthesis was completed by coupling of the side chain through two avenues: a known Still-Gennari olefination and a new Z-selective aldol/dehydroselenation reaction. Both procedures were highly selective and provided the natural product.

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Figures

Figure 1
Figure 1
Leucascandrolide A.
Figure 2
Figure 2
Second generation retrosynthesis of leucascandrolide A.
Figure 3
Figure 3
Rationale for the OH/OMe selectivity of MAP reactions.
Scheme 1
Scheme 1
Two variants of the Mukaiyama aldol-Prins reactions.
Scheme 2
Scheme 2
Synthesis of the 2,6-trans THP.
Scheme 3
Scheme 3
Completion of the aldehyde MAP coupling partner.
Scheme 4
Scheme 4
Completion of a formal synthesis.
Scheme 5
Scheme 5
Completion of the total synthesis by aldol reaction and dehydroselenation.
Scheme 6
Scheme 6
Mechanistic rationale: Aldehyde MAP reactions.
Scheme 7
Scheme 7
Mechanistic rationale: Acetal MAP reactions.
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References

    1. D'Ambrosio M, Guerriero A, Debitus C, Pietra F. Helv Chim Acta. 1996;79:51–60.

    1. This particular class of sponges typically produces compounds consisting of 2-amino imidazoles. See reference .

    1. Hornberger KR, Hamblett CL, Leighton JL. J Am Chem Soc. 2000;122:12894–12895.
    1. Paterson I, Tudge M. Angew Chem, Int Ed. 2003;42:343–347. - PubMed
    2. Paterson I, Tudge M. Tetrahedron. 2003;59:6833–6849.
    1. Wang Y, Janjic J, Kozmin SA. Pure Appl Chem. 2005;77:1161–1169.
    2. Wang Y, Janjic J, Kozmin SA. J Am Chem Soc. 2002;124:13670–13671. - PubMed

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