A Modular Approach to the Antifungal Sphingofungin Family: Concise Total Synthesis of Sphingofungin A and C
Open Access
- 22 October 2021
- journal article
- research article
- Published by Wiley in Angewandte Chemie
- Vol. 61 (5), e202112616
- https://doi.org/10.1002/anie.202112616
Abstract
Sphingofungins are fungal natural products known to inhibit the biosynthesis of sphingolipids which play pivotal roles in various cell functions. Here, we report a short and flexible synthetic approach towards the sphingofungin family. Key step of the synthesis was a decarboxylative cross-coupling reaction of chiral sulfinyl imines with a functionalized tartaric acid derivative, which yielded the core motive of sphingofungins carrying four consecutive stereocenters and a terminal double bond. Subsequent metathesis reaction allowed for the introduction of different side chains of choice resulting in a total of eight sphingofungins, including for the first time sphingofungin C (eight steps from commercially available protected tartaric acid with an overall yield of 6%) and sphingofungin A (ten steps). All newly synthesized derivatives were tested for their antifungal, cell proliferative and antiparasitic activity unraveling their structure-activity relations.Funding Information
- Leibniz-Institut für Naturstoff-Forschung und Infektionsbiologie – Hans-Knöll-Institut
- Deutsche Forschungsgemeinschaft (BE 4799/2-1)
- Horizon 2020 Framework Programme (802736, MORPHEUS)
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