Antidiabetic profiling of veramycins, polyketides accessible by biosynthesis, chemical synthesis and precursor-directed modification

Dardić, Denis; Böhringer, Nils; Plaza, Alberto; Zubeil, Florian; Pohl, Juliane C.S.; Sommer, Svenja; Padva, Leo; Becker, Jonathan; Patras, Maria A.; Bill, Mona-Katharina; Kurz, Michael; Toti, Luigi; Görgens, Sven W.; Schuler, Sören M. M.; Billion, André; Schwengers, Oliver; Wohlfart, Paulus; Goesmann, Alexander; Tennagels, Norbert; Vilcinskas, Andreas; Hammann, Peter; Schäberle, Till F.; Bauer, Armin

doi:10.1039/d1qo01652k

Cited by 9 publications

(23 citation statements)

References 35 publications

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“…ST157608, which features the same isochroman core as the panowamycins and TM-135. [8] Taking advantage intermediate 12, a Wacker oxidation produced 44, which was not spectroscopically consistent with veramycin F (Figure 8). Lactone 45, derived from CÀ H insertion minor isomer 39, was also oxidized to produce 46, which matched the NMR spectrum reported in the isolation publication, thereby completing the asymmetric synthesis and structural reassignment of the relative configuration of veramycin F (46).…”

Section: Methodsmentioning

confidence: 99%

“…Schäberle and Bauer recently reported the isolation of a new polyketide natural product, veramycin F ( 46 ), from Streptomyces sp. ST157608, which features the same isochroman core as the panowamycins and TM‐135 [8] . Taking advantage of intermediate 12 , a Wacker oxidation produced 44 , which was not spectroscopically consistent with veramycin F (Figure 8).…”

Section: Figurementioning

confidence: 99%

“…Specifically, our method provides a single cis ‐diastereomer at C10 and C11 in all cases with high enantioselectivity and without competing Stevens rearrangement. As such, this method provides an excellent strategy for synthesizing the panowamycins and offers some benefits over traditional approaches in polyketide natural products synthesis; most notably, it avoids the use of chiral auxiliaries (Figure 2A) [8, 11, 28] …”

Section: Figurementioning

confidence: 99%

“…[9] Known Streptomyces metabolite NFAT-133 (6) was also isolated in this work and appeared to be related to the panowamycins, benwamycins, and veramycins. [8,10,11] The polyketide natural product 6 has been the subject of several publications resulting in the unambiguous determination of its relative and absolute configuration. [11,12] Recently, Mahmud and co-workers have determined the biosynthetic pathway to NFAT-133 and, in a more recent publication, have proposed a revised relative and absolute structure for panowamycin A (3) based on updated NMR analysis and CD spectroscopy.…”

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confidence: 99%

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Divergent Asymmetric Synthesis of Panowamycins, TM‐135, and Veramycin F Using C−H Insertion with Donor/Donor Carbenes

et al. 2022

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Panowamycins are a group of isochroman‐based natural products first isolated from Streptomyces sp. K07‐0010 in 2012 by Satoshi Ōmura and co‐workers that exhibit modest anti‐trypanosomal activity. Herein we demonstrate the first syntheses of these natural products and their epimers. Stereoselective dirhodium‐catalyzed C−H insertion reactions with a donor/donor carbene construct the substituted isochroman core in the key bond‐forming step. The syntheses are completed without the use of protecting groups and feature a late‐stage Wacker oxidation. Incongruent NMR spectra between natural and synthetic samples revealed the structural misassignment of panowamycin A and veramycin F. Computational NMR studies suggested panowamycin A to be an alternate diastereomer, which was confirmed by synthesizing this isomer. Concurrent with this work, in 2021 Mahmud and co‐workers came to the same conclusion with an updated NMR analysis of panowamycin A. In a divergent, asymmetric sequence, we report the synthesis of panowamycin A, panowamycin B, TM‐135, and veramycin F.

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Section: Methodsmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

Section: Figurementioning

confidence: 99%

mentioning

confidence: 99%

See 2 more Smart Citations

Divergent Asymmetric Synthesis of Panowamycins, TM‐135, and Veramycin F Using C−H Insertion with Donor/Donor Carbenes

et al. 2022

View full text Add to dashboard Cite

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“…ST157608, which features the same isochroman core as the panowamycins and TM-135. [8] Taking advantage of intermediate 12, a Wacker oxidation produced 44, which was not spectroscopically consistent with veramycin F (Figure 8). Lactone 45, derived from CÀ H insertion minor isomer 39, was also oxidized to produce 46, which matched the NMR spectrum reported in the isolation publication, thereby completing the asymmetric synthesis and structural reassignment of the relative configuration of veramycin F (46).…”

Section: Methodsmentioning

confidence: 99%

Divergent Asymmetric Synthesis of Panowamycins, TM‐135, and Veramycin F Using C−H Insertion with Donor/Donor Carbenes

et al. 2022

View full text Add to dashboard Cite

Panowamycins are a group of isochromanbased natural products first isolated from Streptomyces sp. K07-0010 in 2012 by Satoshi Ōmura and co-workers that exhibit modest anti-trypanosomal activity. Herein we demonstrate the first syntheses of these natural products and their epimers. Stereoselective dirhodiumcatalyzed CÀ H insertion reactions with a donor/donor carbene construct the substituted isochroman core in the key bond-forming step. The syntheses are completed without the use of protecting groups and feature a latestage Wacker oxidation. Incongruent NMR spectra between natural and synthetic samples revealed the structural misassignment of panowamycin A and veramycin F. Computational NMR studies suggested panowamycin A to be an alternate diastereomer, which was confirmed by synthesizing this isomer. Concurrent with this work, in 2021 Mahmud and co-workers came to the same conclusion with an updated NMR analysis of panowamycin A. In a divergent, asymmetric sequence, we report the synthesis of panowamycin A, panowamycin B, TM-135, and veramycin F.

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Cytochrome P450 Catalyzes Benzene Ring Formation in the Biosynthesis of Trialkyl‐Substituted Aromatic Polyketides

Zhao

Wei

et al. 2022

Angewandte Chemie

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Lorneic acid and related natural products are characterized by a trialkyl-substituted benzene ring. The formation of the aromatic core in the middle of the polyketide chain is unusual. We characterized a cytochrome P450 enzyme that can catalyze the hallmark benzene ring formation from an acyclic polyene substrate through genetic and biochemical analysis. Using this P450 as a beacon for genome mining, we obtained 12 homologous type I polyketide synthase (PKS) gene clusters, among which two gene clusters are activated and able to produce trialkyl-substituted aromatic polyketides. Quantum chemical calculations were performed to elucidate the plausible mechanism for P450-catalyzed benzene ring formation. Our work expands our knowledge of the catalytic diversity of cytochrome P450.

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Antidiabetic profiling of veramycins, polyketides accessible by biosynthesis, chemical synthesis and precursor-directed modification

Abstract: New polyketides, termed veramycins, were isolated along with their known congeners NFAT-133 and TM-123. Total synthesis from a central building block was accomplished, the BGC identified and a biosynthetic pathway for this molecule class proposed.

Cited by 9 publications

References 35 publications

Divergent Asymmetric Synthesis of Panowamycins, TM‐135, and Veramycin F Using C−H Insertion with Donor/Donor Carbenes

Divergent Asymmetric Synthesis of Panowamycins, TM‐135, and Veramycin F Using C−H Insertion with Donor/Donor Carbenes

Divergent Asymmetric Synthesis of Panowamycins, TM‐135, and Veramycin F Using C−H Insertion with Donor/Donor Carbenes

Cytochrome P450 Catalyzes Benzene Ring Formation in the Biosynthesis of Trialkyl‐Substituted Aromatic Polyketides

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