Biomimetic synthesis
Biomimetic synthesis is an area of
biosynthetic pathway.[1][2] The earliest generally cited example of a biomimetic synthesis is Sir Robert Robinson's organic synthesis of the alkaloid tropinone.[3]
A more recent example is
biocatalyst (e.g., a purely proteinaceous catalyst, a metal or other cofactor bound to an enzyme, or a ribozyme) can be said to be accomplishing a biomimetic synthesis, where design and characterization of such catalytic systems has been termed biomimetic chemistry.[8][9][10]
Synthesis of proto-daphniphylline
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Proto-daphniphylline is a precursor in the
molecular structure making it a challenging target for conventional organic synthesis methods due to the fused ring structure and the spiro carbon centre. Based on a proposed biosynthesis pathway of proto-daphniphylline from squalene, Clayton Heathcock and co-workers developed a remarkably elegant and short total synthesis of proto-daphniphylline from simple starting materials.[11]
This is an example of how biomimetic synthesis can simplify the total synthesis of a complex natural product.
The key step in Heathcock's synthetic route involves a cyclization of acyclic dialdehydes A or B to form proto-daphniphylline. Both dialdehydes (A or B) have carbon skeletons analogous to squalene and can be synthesized from simple starting materials. Treating A or B with a sequence of simple reagents containing
Diels-Alder reaction
formed intermediate E which was further converted to the final product under the reaction conditions.
Examples of biomimetic syntheses in Wikipedia
- carpanone, via the Chapman approach
- spirotryprostatin B, via the Ganesan approach
- endiandric acid, see Biomimetic Total synthesis, via Nicolaou approach
Further literature examples of biomimetic syntheses
- Merck synthesis of nakiterpiosin-type C-nor-D-homosteroids, e.g., Structural: Cleaved, contracted, and expanded rings (seco-, nor-, and homosteroids), via C-13 atom migration[12]
- Heathcock synthesis of squalene-derived daphniphylline-type alkaloids, via tetracyclization or pentacyclization cascades[13][14]
References
- PMID 14695603.
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- .
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- ISBN 9780470719121.
- .
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- PMID 18784073.
- PMID 12642670.
- .
- S2CID 37777797.
- ISBN 978-3-642-34065-9.
- .
- .
Further reading
- Poupon E, Nay B, eds. (2011). Biomimetic Organic Synthesis. Alkaloids. Vol. 1. Wiley-VCH Verlag GmbH & Co. KGaA. ISBN 978-3-527-32580-1.
- Ashely E (January 5, 2004). "Biomimetic Synthesis of Natural Products" (PDF). Literature Seminar, Stoltz Research Group. California Institute of Technology. Archived from the original (PDF) on June 23, 2010. Retrieved November 24, 2013.
