Synthesis of the C1‘−C11‘Segment of Leucascandrolide A

Peter Wipf; Thomas H. Graham

doi:10.1021/jo005787q

Formal Synthesis of Leucascandrolide A.

ChemInform ◽

10.1002/chin.200351211 ◽

2003 ◽

Vol 34 (51) ◽

Author(s):

David R. Williams ◽

Scott V. Plummer ◽

Samarjit Patnaik

Keyword(s):

Leucascandrolide A ◽

Formal Synthesis

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ChemInform Abstract: Synthesis of the C1-C13 Fragment of Leucascandrolide A.

ChemInform ◽

10.1002/chin.200024135 ◽

2010 ◽

Vol 31 (24) ◽

pp. no-no

Author(s):

Michael T. Crimmins ◽

Charlotte A. Carroll ◽

Bryan W. King

Keyword(s):

Leucascandrolide A

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The Rychnovsky Synthesis of Leucascandrolide A

Organic Synthesis ◽

10.1093/oso/9780199764549.003.0087 ◽

2011 ◽

Author(s):

Douglass Taber

Keyword(s):

Vinyl Ether ◽

Absolute Configuration ◽

Secondary Alcohol ◽

Primary Alcohol ◽

Addition Product ◽

Cyclic Ether ◽

Acid Activation ◽

Leucascandrolide A ◽

Stereogenic Centers ◽

Bromide Ion

The macrolactone leucascandrolide A 4, isolated from the calcareous sponge L. caveolata, has both cytotoxic and antifungal activity. The key step in the synthesis of 4 reported (J. Org. Chem. 2007, 72, 5784) by Scott D. Rychnovsky of the University of California, Irvine, was the stereoselective condensation of the aldehyde 1 with the allyl vinyl ether 2 to give 3. The cyclic ether of 1 was assembled from the crotyl addition product 5. Tandem Ru-catalyzed metathesis/hydrogenation converted 5 to the lactone 6. Reduction of 6 to the lactol followed by activation as the acetate gave 7, axial-selective condensation of which with the enol ether 8 delivered the enone 9. Diastereoselective Itsuno-Corey reduction of 9 followed by protecting group exchange and oxidation then gave 1, containing four of the eight stereogenic centers of leucascandrolide A 4. The vinyl ether 2 was readily prepared from the corresponding homoallylic alcohol. Condensation of 1 with 2 involved Lewis acid activation of the aldehyde, addition of the resulting carbocation to the vinyl ether, and cyclization with trapping by bromide ion. In this process, the other four of the eight stereogenic centers were assembled. Three of those centers were formed in the course of the reaction. While stereocontrol was not perfect, the route is pleasingly succinct, so practical quantities of diastereomerically pure 3 could be prepared. To complete the synthesis, the secondary alcohol of 3 was methylated. Selective desilyation of the primary alcohol followed by oxidation and desilylation then set the stage for the Mitsunobu macrolactonization. The intermediates in the Mitsunobu reaction are such that the lactonization can proceed with either inversion of absolute configuration at the secondary center, or retention. While the usually-employed Ph3P gave the lactone with retention of absolute configuration, Bu3P led to clean inversion. The last challenge was the establishment of the (Z) alkene of the side chain. This was accomplished using the Toru protocol. Coupling of the secondary bromide with the Cs salt 12 proceeded with inversion of absolute configuration, to give 13.

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Total Synthesis of Leucascandrolide A.

ChemInform ◽

10.1002/chin.200313200 ◽

2003 ◽

Vol 34 (13) ◽

Author(s):

Alec Fettes ◽

Erick M. Carreira

Keyword(s):

Total Synthesis ◽

Leucascandrolide A

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Stereocontrolled Total Synthesis of (+)-Leucascandrolide A

ChemInform ◽

10.1002/chin.200319196 ◽

2003 ◽

Vol 34 (19) ◽

Author(s):

Ian Paterson ◽

Matthew Tudge

Keyword(s):

Total Synthesis ◽

Leucascandrolide A

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Chemoselective reactions: Toward the synthesis of biologically active natural products with anticancer activities

Pure and Applied Chemistry ◽

10.1351/pac200880081683 ◽

2008 ◽

Vol 80 (8) ◽

pp. 1683-1691 ◽

Cited By ~ 16

Author(s):

Sébastien Reymond ◽

Laurent Ferrié ◽

Amandine Guérinot ◽

Patrice Capdevielle ◽

Janine Cossy

Keyword(s):

Natural Products ◽

Coupling Reaction ◽

Cross Coupling ◽

Biologically Active ◽

Synthetic Approach ◽

Anticancer Activities ◽

Leucascandrolide A ◽

Cross Coupling Reaction ◽

Palladium Catalyzed ◽

Active Natural

Leucascandrolide A and migrastatin were synthesized efficiently by using chemoselective reactions such as olefin metatheses. The use of an iron-catalyzed cross-coupling reaction overcame difficulties encountered with palladium-catalyzed processes in our synthetic approach toward spirangien A.

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