An Expedient, Scalable Synthesis of the Natural Product l-Anserine

Abstract

To date, the synthesis of l-anserine has relied on the use of naturally occurring 1-methyl-l-histidine as a precursor, however its high cost prevents its use in the large-scale synthesis of l-anse­rine. With this in mind, we report herein a concise and efficient synthetic strategy, employing the 160-fold less expensive, l-histidine methyl ester dihydrochloride as a starting material, to afford the title compound in an overall yield of 88%, over four reaction steps.

Key words

natural products - peptides - amino acids - coupling

References

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11

l-Anserine (1) is obtained from natural sources using a hot water extraction procedure, affording typical recoveries of 45 g of l-anserine hydrochloride (8) from 10 kg of bonito extract (0.45 wt%).

17

The free amine 1 was found to be stable for extended periods of time when stored under N₂, however, it rapidly sublimed when exposed to air; structural analysis confirmed that no decomposition had occurred.