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. 2014 Jan 3;16(1):94-7.
doi: 10.1021/ol403078e. Epub 2013 Dec 6.

Radical [3 + 2]-annulation of divinylcyclopropanes: rapid synthesis of complex meloscine analogs

Hanmo Zhang  1 , Kyu Ok Jeon, E Ben Hay, Steven J Geib, Dennis P Curran, Matthew G LaPorte
Affiliations

Radical [3 + 2]-annulation of divinylcyclopropanes: rapid synthesis of complex meloscine analogs

Hanmo Zhang et al. Org Lett. .

Abstract

A radical [3 + 2]-divinylcyclopropane annulation cascade has been extended to encompass five D-ring variants of the meloscine/epimeloscine core structure. Representative ABCD tetracyclic intermediates were further elaborated with novel substituted E-rings through subsequent transformations of advanced intermediates that provided opportunities for late-stage variation of the B-ring (lactam) N-substituents which were also developed.

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Figures

Figure 1
Figure 1
Structures of meloscine 1a, epimeloscine 2s, and scandine 3.
Figure 2
Figure 2
Fragments in the design of the pentacyclic analogs
Figure 3
Figure 3
ORTEP structure of amine 18b.
Scheme 1
Scheme 1
Divinylcyclopropane cascade cyclization with likely intermediates.
Scheme 2
Scheme 2
Synthesis of annulation precursors 16a–c.
Scheme 3
Scheme 3
Completion of the D-ring analog synthesis. a) crude product used directly in the next step; b) two-step yield
Scheme 4
Scheme 4
Synthesis of E-ring analogs.
Scheme 5
Scheme 5
Synthesis of substituted B-ring analogs.
See this image and copyright information in PMC

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