Total Synthesis of Grossularines1 and 2 - PowerPoint PPT Presentation

Title: Total Synthesis of Grossularines1 and 2


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Total Synthesis of Grossularines-1 and -2

• J. Org. Chem., 1995, 60, 5899-5904

Ricardo Barata 13309 - LQA
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Grossularines-1 and -2
Isolated in 1989 from Dendroa grossularia
First naturally occuring pyrido2,3-bindoles
Structures determined by spectroscopic evidence
and X-Ray analysis (though only for
Grossularine-2)
Chalenging due to their unique tetracyclic
structure.
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Retrosynthesis
Grossularine 1 R1 NMe2 R2 H R3
3-indolyl Grossularine 2 R1 NMe2 R2 H R3
p-hydroxyphenyl
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Retrosynthesis
Next we considered that the tetracyclic
pyrido2,3-bindole 3 would be obtained by a
thermal electrocyclic reaction of
3-imidazolindole-2-isocyanate 4 (...)
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Retrosynthesis
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Synthesis
h83
h82
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Synthesis
h87
h88
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Synthesis
h94
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Synthesis
1 método
2 métodos
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Synthesis
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(Method A)

• (19a) 93
• h (19b) 77

h19
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Synthesis

• (19a) 37
• h (19b) 63

• (19a) 61
• h (19b) 51

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Mechanism - Arylstannane
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Mechanism Stille Coupling
Stille Coupling
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Mechanism Isocyanate Formation
Wittig-type mechanism
-N2
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Mechanism - Cyclization
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Conclusions
This approach provides an effective route to the
imidazo4,54,4pyrido2,3-bindole ring
First total synthesis of Grossularine-1 (h28,
from iodoindole 6)
Improvement of total synthesis of Grossularine-2
(h33, from iodoindole 6).
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Bibliography
T. Choshi et al, J. Org. Chem, 1995, 60, 5899-5904
Clayden, Greeves, Warren and Wothers, Organic
Chemistry, 1st edition, Oxford University Press,
2001
Carruthers and Coldham, Modern Methods of Organic
Synthesis, 4th edition, Cambridge University
Press, 2004