Synthesis of the Spiroiminal Moiety of Marineosins A and B

Cai, Xiao-Chuan; Wu, Xiaoxing; Snider, Barry B.

doi:10.1021/ol100333d

Cited by 27 publications

(25 citation statements)

References 14 publications

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“…18 Sequence alignments of MarG with other C–C bond-forming non-heme iron Rieske oxygenases such as RedG, McpG, and RphG involved in the biosynthesis of natural products 3 , 4 , and roseophilin, respectively, together with hydroxylating non-heme iron Rieske oxygneases show that all have conserved N-terminal CXH and CXXH motifs. However, MarG and its homologues have an EXHX4H motif at their C-terminal end rather than the DXHX4H motif characteristic to Rieske hydroxylases (Supplementary Figure S40).…”

Section: Results and Discussionmentioning

confidence: 99%

Elucidation of Final Steps of the Marineosins Biosynthetic Pathway through Identification and Characterization of the Corresponding Gene Cluster

et al. 2014

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The marine Streptomyces sp. CNQ-617 produces two diastereomers, marineosins A and B. These are structurally related to alkyl prodiginines, but with a more complex cyclization and an unusual spiroaminal skeleton. We report the identification of the mar biosynthetic gene cluster and demonstrate production of marineosins through heterologous expression in a S. venezuelae host named JND2. The mar cluster shares the same gene organization and has high homology to the genes of the red cluster (which directs the biosynthesis of undecylprodiginine) but contains an additional gene, named marA. Replacement of marA in the JND2 strain leads to the accumulation of premarineosin, which is identical to marineosin with the exception that the middle pyrrole (Ring B) has not been reduced. The final step of the marineosin pathway is thus a MarA catalyzed reduction of this ring. Replacement of marG (a homologue of redG that directs undecylprodiginine cyclization to give streptorubin B) in the JND2 strain leads to the loss of all spiroaminal products and the accumulation of 23-hydroxyundecylprodiginine and a shunt product, 23-ketoundecylprodiginine. MarG thus catalyzes the penultimate step of the marineosin pathway catalyzing conversion of 23-hydroxyundecylprodiginine to premarineosin. The preceding steps of the biosynthetic marineosin pathway likely mirror that in the red-directed biosynthetic process, with the exception of the introduction of the hydroxyl functionality required for spiroaminal formation. This work presents the first experimentally supported scheme for biosynthesis of marineosin and provides a new biologically active molecule, premarineosin.

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Section: Results and Discussionmentioning

confidence: 99%

Elucidation of Final Steps of the Marineosins Biosynthetic Pathway through Identification and Characterization of the Corresponding Gene Cluster

et al. 2014

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“…Later the same year, Snider and co-workers 156 reported a different route toward the synthesis of marineosins and put forward an alternative biosynthetic proposal, involving abstraction of a hydrogen atom from C-8′ of undecylprodigiosin 17 to create a radical that undergoes cyclization to generate intermediate 317 (Scheme 36). Intramolecular hydrogen transfer via a six-membered transition state would convert intermediate 317 to the C-10′ radical 318 , which could be trapped by enzyme-mediated hydroxylation to give 319 .…”

Section: Biosynthesismentioning

confidence: 99%

Structure, Chemical Synthesis, and Biosynthesis of Prodiginine Natural Products

et al. 2016

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The prodiginine family of bacterial alkaloids is a diverse set of heterocyclic natural products that have likely been known to man since antiquity. In more recent times, these alkaloids have been discovered to span a wide range of chemical structures that possess a number of interesting biological activities. This review provides a comprehensive overview of research undertaken toward the isolation and structural elucidation of the prodiginine family of natural products. Additionally, research toward chemical synthesis of the prodiginine alkaloids over the last several decades is extensively reviewed. Finally, the current, evidence-based understanding of the various biosynthetic pathways employed by bacteria to produce prodiginine alkaloids is summarized.

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“…[1,3] Shortly thereafter, Snider proposed an alternative, prodigiosin-inspired biosynthesis requiring only a two-electron oxidation, which he then validated in a model system of the spiroiminal moeity of 1 . [4] Thus, despite significant interest from the synthetic community, limited synthetic efforts have been reported en route to a total synthesis of 1 .…”

Section: Introductionmentioning

confidence: 99%

Towards the Total Synthesis of Marineosin A: Construction of the Macrocyclic Pyrrole and an Advanced, Functionalized Spiroaminal Model

et al. 2013

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Herein, we describe the enantioselective construction of the 12-membered macrocyclic pyrrole core 4 of marineosin A in 5.1% overall yield from (S)-propylene oxide. The route features a key Stetter reaction to install a 1,4-diketone, which is then subjected to Paal-Knorr pyrrole synthesis and ring closing metathesis (RCM) to afford macrocycle 4. A divergence point in the synthetic scheme also enabled access to a highly functionalized spiroaminal model system 8 via an acid-mediated hydroxyketoamide cyclization strategy.

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Synthesis of the Spiroiminal Moiety of Marineosins A and B

Cited by 27 publications

References 14 publications

Elucidation of Final Steps of the Marineosins Biosynthetic Pathway through Identification and Characterization of the Corresponding Gene Cluster

Elucidation of Final Steps of the Marineosins Biosynthetic Pathway through Identification and Characterization of the Corresponding Gene Cluster

Structure, Chemical Synthesis, and Biosynthesis of Prodiginine Natural Products

Towards the Total Synthesis of Marineosin A: Construction of the Macrocyclic Pyrrole and an Advanced, Functionalized Spiroaminal Model

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