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Published on: May 15, 2019
Chemoenzymatic deacylation of ramoplanin
Raffaella Gandolfi1, Flavia Marinelli, Enzio Ragg
1Dipartimento di Scienze Farmaceutiche, Via Venezian 21, 20133 Milano, Italy.
Bioorganic & Medicinal Chemistry Letters
|July 17, 2012
Summary
A novel chemoenzymatic method for ramoplanin A2 deacylation was developed using an Actinoplanes utahensis acylase. This process achieved an 80% yield, outperforming traditional chemical deacylation methods.
Area of Science:
- Biotechnology
- Organic Chemistry
- Enzymology
Background:
- Ramoplanin A2 is a lipoglycopeptide antibiotic with significant therapeutic potential.
- Existing chemical deacylation methods for ramoplanin A2 can be harsh and inefficient.
- Enzymatic approaches offer a milder and potentially more selective alternative for modifying complex molecules.
Purpose of the Study:
- To establish and optimize a chemoenzymatic deacylation process for ramoplanin A2.
- To compare the efficiency and yield of the chemoenzymatic method with existing chemical deacylation techniques.
- To explore the utility of Actinoplanes utahensis NRRL 12052 acylase in modifying complex antibiotic structures.
Main Methods:
- Ramoplanin A2 was protected with a Boc group and hydrogenated to form Boc-protected tetrahydroramoplanin.
- The protected intermediate was then subjected to enzymatic deacylation using an acylase from Actinoplanes utahensis NRRL 12052.
- The overall yield of the chemoenzymatic process was determined and compared to chemical methods.
Main Results:
- The chemoenzymatic deacylation of ramoplanin A2 was successfully achieved for the first time.
- The process yielded Boc-protected tetrahydroramoplanin, demonstrating selective deacylation.
- An overall yield of 80% was obtained, which is favorable compared to previous chemical deacylation results.
Conclusions:
- Chemoenzymatic deacylation using Actinoplanes utahensis acylase provides an efficient and high-yielding route to modified ramoplanin A2 derivatives.
- This enzymatic approach represents a significant advancement over traditional chemical methods for ramoplanin A2 modification.
- The developed method holds promise for the synthesis of novel lipoglycopeptide analogs with potential therapeutic applications.
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