A new strategy for the stereoselective synthesis of unnatural α-amino acids

A new method for the synthesis of racemic non-proteinogenic α-amino acids has been developed, which involves (i) hetero-Diels-Alder addition of ethyl 2-nitrosoacrylate to electron rich alkenes such as enol ethers, enamines and allylsilanes, (ii) NaCNBH₃ reduction of the CN bond in the oxazines thus generated, the stereochemistry of the products being controlled by epimerisation of the thermodynamically less stable isomer to the more stable one, (iii) protection of the N-H group as N-Boc and (iv) finally, N-O bond cleavage of both free and protected products to give proline or bis-homoserine derivatives, respectively. An example with concomitant reduction of the carboxylate group, resulting in the formation of the respective amino alcohol is reported. Applying this methodology to a homochiral enol ether, the protected parent d-proline was prepared in enantiomerically pure form, whereas the asymmetric synthesis of the respective bis-homoserine was unsuccessful.     

The hetero-Diels-Alder addition of ethyl 2-nitrosoacrylate to electron-rich alkenes as a route to unnatural α-amino acids

A new method for the stereoselective synthesis of nonproteinogenic α-amino acids has been developed, which involves hetero-Diels-Alder addition of ethyl 2-nitrosoacrylate to electron-rich alkenes, such as enol ethers, enamines and allylsilanes, and a further two or three step manipulation of the resulting oxazines.     

Efficient synthesis of syringolides, secosyrins, and syributins through a common approach

A new common synthetic approach toward the elicitors syringolides and their related natural products, secosyrins and syributins, is described here. This uses d-arabinose as starting material and efficiently delivers the targeted compounds through a sequential tandem HWE olefination-lactonization process and an IHMA reaction.     

A new scalable synthesis of entecavir

A new synthesis of entecavir from d-glucose in an average total yield of 3.5% was achieved via an intramolecular nitrile oxide cycloaddition (INOC) reaction and a Peterson olefination as key-steps. The present process was designed for industrial application, using widely available raw materials, simple and cheap reagents and avoiding low reaction temperatures, which are very common in the synthetic approaches towards similarly complex structures.