One way of diversifying the 2-azabicyclo[5.3.0]decane structure lies in the introduction of various substitutents at the amine nitrogen. Substituents were introduced either by deprotonation of the amine with sodium hydride and then reacting it with haloalkanes or acyl halides, or by reductive amination of aldehydes or ketones with sodium cyano borohydride.

Ten N-substituted amines and three amides were synthesised. None of the amides had any antifungal activity, which is consistent with our basic concept: An alkaline nitrogen is essential to form a stable analog of the HEI. All of the amines had high antifungal potency, two of them even higher than commercially available antifungals (74 and 75).

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