Lecture 15 Flashcards
(16 cards)
What is the primary focus of the research discussed in Lecture 15?
Synthetic methodology and target-oriented synthesis
The goal is to develop tool molecules to probe disease processes.
What is Spiroleucettadine (SL) and where is it isolated from?
Marine alkaloid isolated from Leucetta sponge
It shows antibacterial activity, particularly against Enterococcus durans.
What were the initial antibacterial activity reports for Spiroleucettadine?
Good activity against Enterococcus durans, better than penicillin MIC
This raised interest in its potential medicinal applications.
What was the significance of confirming the correct structure of Spiroleucettadine?
It is crucial for biological relevance
Incorrect structural assignments can mislead biological evaluations.
Who proposed the revised structure of Spiroleucettadine in 2008?
Crews et al.
This revision was necessary due to earlier misassignments.
What methods were used for structural determination of Spiroleucettadine?
DFT calculations, NMR, X-ray crystallography
These methods helped clarify the correct structure.
What led to the misassignment of the original Spiroleucettadine structure?
Experimental artifact, such as MeOH interference
This highlights the challenges in structural determination.
What was the original aim of the synthetic strategy for Spiroleucettadine?
Confirm spiroleucettadine structure via synthesis
This included synthesizing both the revised and N/O inverted structures.
What is the significance of total synthesis in medicinal chemistry?
Provides unambiguous structural proof, enables SAR studies, provides compounds for biological assays
Total synthesis is resource-intensive but crucial for drug discovery.
What was the outcome of the biological evaluation of synthetic Spiroleucettadine against E. durans?
Showed no antibacterial activity
This was contrary to initial reports of its antibacterial properties.
What type of activity did synthetic Spiroleucettadine show when tested against NCI-60 cancer cell lines?
Nanomolar potency in some lines
This suggests potential anticancer properties.
What preliminary studies suggest about the mode of action of Spiroleucettadine?
Targets the tumor suppressor p53 pathway
This indicates a shift from antibacterial to anticancer activity.
What is target-oriented synthesis?
Synthesizing a complex natural product to confirm structure and enable biological evaluation
It is a critical approach in natural product chemistry.
What common problem in natural products does synthesis and advanced spectroscopy resolve?
Structural misassignments
Accurate structural determination is essential for biological studies.
What role does SAR play in drug discovery?
Key to improving biological activity and understanding mode of action
It involves studying the relationship between structure and activity.
True or False: The total synthesis is not essential for complex natural products.
False
Total synthesis is crucial despite being time-consuming and resource-intensive.
