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NATURAL PRODUCTS - Coggle Diagram
NATURAL PRODUCTS
➧ is bio-synthesized by a living organism (NP producer) though its metabolism
➧ many of them can se synthesized synthetically
➧ the same NP producer may bio-synthesize different NPs depending on its environment
➧ NP can be used in medicine or modern research
⁍ LARGER since they have optimized though evolution
⁍ the don't care about the Lipinski rule
⁍ Much more complex ➝ large number of chiral centers that are difficult to achieve
⁍ Lower number of rotatable bonds because they have the perfect fit so there is no need to adapt to the active site
⁍ High number of rings
⁍ Heavy atom chains and substituents are smaller
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NP discovery
1. Identification of a biological activity from a new NP producer - SCREENING
◆ easy for lower NP producers but more difficult for higher NP producers
2. Purification of the active NP(s) from the NP producer
◆ extraction/purification of an 'activity' from the producer or from a part of it
◆ solvent extraction, preliminary separations, fraction collection and concentration
◆ identification of the fraction containing the 'activity'
3. Dereplication
◆ ensure that you are not rediscovering a natural compound
4. Structural determination
◆ Methods: MS, NMR, X-rays
⇝ Myxobacteria
⇝ Sorangium cellulosum producer (epothilone A and Epothilone B)
⇝ Taxus brevifolia (Taxol)
⇝ Epipedobates tricolor ( Epibatidine)
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MACROCYCLES
compounds containing at least one non-bridged ring with >= 13 covalently connected atoms
(14 membered MC are by far the most common)
natures strategy to macrocycle diversity (typical biosynthesis of a complex natural product) :
- Iterative oligomerization
- Cyclization
- Combination/Conjugation
- Post-modification
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CHAMELEON THEORY
possibility of easily changing between two major conformations (extended and narrow/restricted)
➜ behaves as hydrophilic in aqueous medium and as lipophilic in the membranes
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