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. 2008 Dec 19;73(24):9657-67.
doi: 10.1021/jo801794s.

Total synthesis of (+)-superstolide A

Mariola Tortosa  1 , Neal A Yakelis, William R Roush
Affiliations

Total synthesis of (+)-superstolide A

Mariola Tortosa et al. J Org Chem. .

Abstract

A convergent and highly stereocontrolled total synthesis of the cytotoxic macrolide (+)-superstolide A is described. Key features of this synthesis include the use of bimetallic linchpin 36b for uniting the C(1)-C(15) (43) and the C(20)-C(27) (38) fragments of the natural product, a late-stage Suzuki macrocyclization of 49, and a highly diastereoselective transannular Diels-Alder reaction of macrocyclic octaene 4. In contrast, the intramolecular Diels-Alder reaction of pentaenal 5 provided the desired cycloadduct with lower stereoselectivity (6:1:1).

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Figures

Figure 1
Figure 1
Superstolides A and B
Figure 2
Figure 2
1H nOe interactions in the IMDA adduct 23
Scheme 1
Scheme 1
Retrosynthetic Analysis
Scheme 2
Scheme 2
Synthesis of Allylic Alcohols 7a–b
Scheme 3
Scheme 3
Synthesis of Trienyl Iodide 20
Scheme 4
Scheme 4
Synthesis of the IMDA precursor 22
Scheme 5
Scheme 5
IMDA of Pentaenal 5
Scheme 6
Scheme 6
Elaboration of the IMDA adduct 23
Scheme 7
Scheme 7
Synthesis of iodide 6
Scheme 8
Scheme 8
Revision of the Synthetic Strategy
Scheme 9
Scheme 9
Unexpected Z/E isomerization during Takai olefination of 32
Scheme 10
Scheme 10
Second Generation Retrosynthesis of Superstolide A
Scheme 11
Scheme 11
Studies on the Synthesis of a Bimetallic Linchpin
Scheme 12
Scheme 12
Synthesis of Bimetallic Linchpin 36b
Scheme 13
Scheme 13
Synthesis and Wittig coupling of 35a and aldehyde 37a
Scheme 14
Scheme 14
Synthesis of the C(16)-C(27) Fragment 47
Scheme 15
Scheme 15
Fragment Assembly Strategies
Scheme 16
Scheme 16
Macrolactonization Pathway for Superstolide Synthesis
Scheme 17
Scheme 17
Synthesis of carboxylic acid 53
Scheme 18
Scheme 18
Completion of the Total Synthesis of Superstolide A
See this image and copyright information in PMC

References

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