Mathieson, Jennifer E.
A flexible one-step synthesis of dienamides: approaches towards a total synthesis of the Crocacins.
MSc(R) thesis, University of Glasgow.
Full text available as:
Dienamides are prevalent in many biologically active natural products and pharmaceutical drug leads. A number of different approaches have been reported for the synthesis of dienamides. These mathods have varying degrees of success in terms of yield and selectivity. In particular, the control of double bond geometry presents a significant challenge. Presented, is an efficient one-step synthesis of dienamide units starting from previously established N-formyl imide building blocks.
This approach presents an attractive alternative to other methods available currently in terms of the number of steps, yield and overall simplicity. The one-step approach to the synthesis of dienamides relies on olefination of N-formyl imides through the use of conjugated ylides. A number of final dienamide compounds have been synthesised, characterised and published thus far. In all cases the sole or major isomer observed was the (Z,E)-dienamide.
The Crocacins are a group of linear dipeptides incorporating a reactive N-acyl enamine or enamide unit, crucial to their biological activity. Retrosynthetically, Crocacins A, B and D are derived from Crocacin C via an enamide linkage. It is proposed that Crocacins A, B and D can be synthesised from Crocacin C using the dienamide methodology developed previously. Although several syntheses of the individual members of the Crocacins have been reported, this method represents a potential route to a convergent synthesis for the whole family of compounds. Presented, are the approaches towards the total synthesis of Crocacin C.
Actions (login required)