Total Synthesis of the Cyclic Depsipeptide Vioprolide D Via Its (Z)-Diastereoisomer

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2020 Mar 4

PMID 32126146

Citations 4

Authors

Hanusch A Grab

Volker C Kirsch

Stephan A Sieber

Thorsten Bach

Affiliations

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Abstract

The first total synthesis of vioprolide D was accomplished in an overall yield of 2.0 % starting from methyl (2S)-3-benzyloxy-2-hydroxypropanoate (16 steps in the longest linear sequence). The cyclic depsipeptide was assembled from two building blocks of similar size and complexity in a modular, highly convergent approach. Peptide bond formation at the C-terminal dehydrobutyrine amino acid of the northern fragment was possible via its (Z)-diastereoisomer. After macrolactamization and formation of the thiazoline ring, the (Z)-double bond of the dehydrobutyrine unit was isomerized to the (E)-double bond of the natural product. The cytotoxicity of vioprolide D is significantly higher than that of its (Z)-diastereoisomer.

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Total Synthesis of the Cyclic Depsipeptide Vioprolide D via its (Z)-Diastereoisomer.

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References

Kirsch V, Orgler C, Braig S, Jeremias I, Auerbach D, Muller R . The Cytotoxic Natural Product Vioprolide A Targets Nucleolar Protein 14, Which Is Essential for Ribosome Biogenesis. Angew Chem Int Ed Engl. 2019; 59(4):1595-1600. PMC: 7004033. DOI: 10.1002/anie.201911158. View

Yamashita T, Kuranaga T, Inoue M . Solid-Phase Total Synthesis of Bogorol A: Stereocontrolled Construction of Thermodynamically Unfavored (E)-2-Amino-2-butenamide. Org Lett. 2015; 17(9):2170-3. DOI: 10.1021/acs.orglett.5b00769. View

Mosmann T . Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983; 65(1-2):55-63. DOI: 10.1016/0022-1759(83)90303-4. View

Ward D, Vazquez A, Pedras M . Probing Host-Selective Phytotoxicity: Synthesis and Biological Activity of Phomalide, Isophomalide, and Dihydrophomalide. J Org Chem. 2001; 64(5):1657-1666. DOI: 10.1021/jo982376p. View

Yasuno Y, Nishimura A, Yasukawa Y, Karita Y, Ohfune Y, Shinada T . The stereoselective construction of E- and Z-Δ-Ile from E-dehydroamino acid ester: the synthesis of the phomopsin A tripeptide side chain. Chem Commun (Camb). 2015; 52(7):1478-81. DOI: 10.1039/c5cc08458j. View

Kitagaki J, Shi G, Miyauchi S, Murakami S, Yang Y . Cyclic depsipeptides as potential cancer therapeutics. Anticancer Drugs. 2014; 26(3):259-71. DOI: 10.1097/CAD.0000000000000183. View

MacMillan J, Ernst-Russell M, de Ropp J, Molinski T . Lobocyclamides A-C, lipopeptides from a cryptic cyanobacterial mat containing Lyngbya confervoides. J Org Chem. 2002; 67(23):8210-5. DOI: 10.1021/jo0261909. View

Goto Y, Li B, Claesen J, Shi Y, Bibb M, van der Donk W . Discovery of unique lanthionine synthetases reveals new mechanistic and evolutionary insights. PLoS Biol. 2010; 8(3):e1000339. PMC: 2843593. DOI: 10.1371/journal.pbio.1000339. View

Butler E, Florentino L, Cornut D, Gomez-Campillos G, Liu H, Regan A . Synthesis of macrocyclic precursors of the vioprolides. Org Biomol Chem. 2018; 16(38):6935-6960. DOI: 10.1039/c8ob01756e. View

10.

Yan F, Muller R . Class I Methyltransferase VioH Catalyzes Unusual S-Adenosyl-l-methionine Cyclization Leading to 4-Methylazetidinecarboxylic Acid Formation during Vioprolide Biosynthesis. ACS Chem Biol. 2018; 14(1):99-105. DOI: 10.1021/acschembio.8b00958. View

11.

Grgurina I, Mariotti F . Biosynthetic origin of syringomycin and syringopeptin 22, toxic secondary metabolites of the phytopathogenic bacterium Pseudomonas syringae pv. syringae. FEBS Lett. 1999; 462(1-2):151-4. DOI: 10.1016/s0014-5793(99)01528-8. View

12.

Lu C, Xie F, Shan C, Shen Y . Two novel cyclic hexapeptides from the genetically engineered Actinosynnema pretiosum. Appl Microbiol Biotechnol. 2016; 101(6):2273-2279. DOI: 10.1007/s00253-016-8017-3. View

13.

Boyd D, Sharma N, Malone J, Allen C . New families of enantiopure cyclohexenone cis-diol, o-quinol dimer and hydrate metabolites from dioxygenase-catalysed dihydroxylation of phenols. Chem Commun (Camb). 2009; (24):3633-5. DOI: 10.1039/b905940g. View

14.

Luo S, Kang H, Krunic A, Chen W, Yang J, Woodard J . Trichormamides C and D, antiproliferative cyclic lipopeptides from the cultured freshwater cyanobacterium cf. Oscillatoria sp. UIC 10045. Bioorg Med Chem. 2015; 23(13):3153-62. PMC: 4469202. DOI: 10.1016/j.bmc.2015.04.073. View

15.

Arp J, Gotze S, Mukherji R, Mattern D, Garcia-Altares M, Klapper M . Synergistic activity of cosecreted natural products from amoebae-associated bacteria. Proc Natl Acad Sci U S A. 2018; 115(15):3758-3763. PMC: 5899472. DOI: 10.1073/pnas.1721790115. View

16.

Chen Y, Bilban M, Foster C, Boger D . Solution-phase parallel synthesis of a pharmacophore library of HUN-7293 analogues: a general chemical mutagenesis approach to defining structure-function properties of naturally occurring cyclic (depsi)peptides. J Am Chem Soc. 2002; 124(19):5431-40. DOI: 10.1021/ja020166v. View

17.

Gisin B, MERRIFIELD R . Carboxyl-catalyzed intramolecular aminolysis. A side reaction in solid-phase peptide synthesis. J Am Chem Soc. 1972; 94(9):3102-6. DOI: 10.1021/ja00764a036. View

18.

Roff G, Lloyd R, Turner N . A versatile chemo-enzymatic route to enantiomerically pure beta-branched alpha-amino acids. J Am Chem Soc. 2004; 126(13):4098-9. DOI: 10.1021/ja049499d. View

19.

Hashimoto M, Murakami T, Funahashi K, Tokunaga T, Nihei K, Okuno T . An RNA polymerase inhibitor, cyclothiazomycin B1, and its isomer. Bioorg Med Chem. 2006; 14(24):8259-70. DOI: 10.1016/j.bmc.2006.09.006. View

20.

Stolze S, Kaiser M . Case studies of the synthesis of bioactive cyclodepsipeptide natural products. Molecules. 2013; 18(2):1337-67. PMC: 6270203. DOI: 10.3390/molecules18021337. View