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Biologically Inspired Total Synthesis of Ulbactin F, an Iron-Binding Natural Product.

ABSTRACT: Natural products from environmental microbiomes provide exquisite templates for elucidating biological activity in the search for new drugs. A recently discovered marine Brevibacillus sp. metabolite, ulbactin F, was found to inhibit tumor cell migration and invasion at IC50 < 3 ?M. Herein, we disclose the first total synthesis of ulbactin F and epi-ulbactin F, which was modeled after the biosynthetic pathway. The scaffold bears structural similarity to siderophores of human pathogens but contains a novel tricyclic ring system derived from cysteine. We have found that ulbactin F forms low-affinity metal complexes, with a preference for Fe3+ and Cu2+, which may hint both at its environmental role and its antimetastatic mechanism of action.

SUBMITTER: Shapiro JA

PROVIDER: S-EPMC6456333 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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Biologically Inspired Total Synthesis of Ulbactin F, an Iron-Binding Natural Product.

Shapiro Justin A JA Morrison Kelly R KR Chodisetty Shreya S SS Musaev Djamaladdin G DG Wuest William M WM

Organic letters 20180910 18

Natural products from environmental microbiomes provide exquisite templates for elucidating biological activity in the search for new drugs. A recently discovered marine Brevibacillus sp. metabolite, ulbactin F, was found to inhibit tumor cell migration and invasion at IC<sub>50</sub> < 3 μM. Herein, we disclose the first total synthesis of ulbactin F and epi-ulbactin F, which was modeled after the biosynthetic pathway. The scaffold bears structural similarity to siderophores of human pathogens ...[more]

PMID: 30199265

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