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. Author manuscript; available in PMC: 2020 Nov 1.
Published in final edited form as: Nat Chem. 2019 Sep 23;11(11):972–980. doi: 10.1038/s41557-019-0326-6

Figure 2. Biomimetic synthesis of premalbrancheamide.

Figure 2.

The biomimetic synthesis proceeded through a spontaneous intramolecular [4+2] Diels-Alder reaction from key azadiene intermediate 12 to produce a racemic mixture of syn-premalbrancheamides (1). Zwitterion 11 arises from spontaneous oxidation of 9 and was initially reasoned to be a non-physiological by-product. After discovering that 11 was the preferred substrate of MalC, non-enzymatic chemical reduction by NADH was explored providing 1 in 76% yield from 11. Only optically pure (+)-1 has been isolated from Malbranchea aurantiaca. See SI for complete methods.