A modular approach to the antifungal Sphingofungin family: Concise total synthesis of Sphingofungin A and C.

Raguž L, Peng CC, Kaiser M, Görls H, Beemelmanns C* (2021) A modular approach to the antifungal Sphingofungin family: Concise total synthesis of Sphingofungin A and C. Angew Chem Int Ed [Accepted]

*equal contribution

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.

Leibniz-HKI-Authors

Christine Beemelmanns
Luka Raguž
Chia-Chi Peng

Identifier

doi: 10.1002/anie.202112616

PMID: 34677894