Total synthesis of aplyronine C
Ian Paterson1, Sarah J Fink, Lydia Y W Lee
1University Chemical Laboratory, University of Cambridge , Lensfield Road, Cambridge CB2 1EW, U.K.
Organic Letters
|June 5, 2013
Summary
A total synthesis of marine macrolide aplyronine C was achieved using stereocontrolled aldol reactions. This study details the construction of aplyronine C and novel side chain analogs.
Area of Science:
- Organic Chemistry
- Natural Product Synthesis
- Medicinal Chemistry
Background:
- Marine macrolides, such as aplyronine C, are complex natural products with significant cytotoxic activity.
- The total synthesis of such molecules presents substantial challenges in stereochemical control and structural complexity.
Purpose of the Study:
- To describe a highly stereocontrolled total synthesis of the marine macrolide aplyronine C.
- To report the synthesis of two novel C21-C34 side chain analogs of aplyronine C.
Main Methods:
- Exploitation of aldol methodology for stereochemical control.
- A key boron-mediated aldol coupling between an N-vinylformamide-bearing methyl ketone and a macrocyclic aldehyde to construct the side chain.
Main Results:
- Successful and highly stereocontrolled total synthesis of aplyronine C.
- Efficient synthesis of two previously undescribed C21-C34 side chain analogs, expanding the scope of aplyronine derivatives.
Conclusions:
- The developed synthetic route provides a viable pathway to aplyronine C and its analogs.
- The methodology highlights the power of boron-mediated aldol reactions in complex molecule synthesis.
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