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09:04
A Direct, Early Stage Guanidinylation Protocol for the Synthesis of Complex Aminoguanidine-containing Natural Products
Published on: September 9, 2016
Synthesis of jenamidines A1/A2
Barry B Snider1, Jeremy R Duvall
1Department of Chemistry MS 015, Brandeis University, Waltham, Massachusetts 02454-9110, USA. snider@brandeis.edu
Organic Letters
|September 24, 2005
Summary
This study reports the first synthesis of jenamidines A1/A2, confirming their structural reassignment. The multi-step process involved creating a vinylogous urea intermediate, followed by acylation and hydrolysis.
Area of Science:
- Organic Synthesis
- Medicinal Chemistry
- Natural Product Synthesis
Background:
- Jenamidines A1/A2 are natural products with a unique structure.
- Previous structural assignments for jenamidines A1/A2 were uncertain.
Purpose of the Study:
- To achieve the first total synthesis of jenamidines A1/A2.
- To confirm the proposed structure of jenamidines A1/A2 through synthesis.
Main Methods:
- Synthesis of a key vinylogous urea intermediate (19) via enolate addition to cyanamide methyl ester or reaction with tert-butyl cyanoacetate.
- Acylation of the vinylogous urea with acid chloride 31d.
- Hydrolysis of tert-butyl ester and decarboxylation.
- Mild basic hydrolysis of the methoxyacetate ester.
Main Results:
- Successful synthesis of jenamidines A1/A2 (3) in 45% overall yield.
- Two distinct routes were explored for the vinylogous urea intermediate, with one yielding 50% and the other 27%.
Conclusions:
- The synthetic route provides definitive confirmation of the reassigned structure of jenamidines A1/A2.
- This work establishes a foundational synthetic strategy for jenamidine analogs.
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