Total Synthesis of Biseokeaniamides A-C and Late-stage Electrochemically-enabled Peptide Analogue Synthesis

Overview

Journal Chem Sci

Publisher Royal Society of Chemistry

Specialty Chemistry

Date 2021 Jun 7

PMID 34094328

Citations 6

Authors

Yutong Lin

Lara R Malins

Affiliations

Soon will be listed here.

Abstract

The first total synthesis of cytotoxic cyanobacterial peptide natural products biseokeaniamides A-C is reported employing a robust solid-phase approach to peptide backbone construction followed by coupling of a key thiazole building block. To rapidly access natural product analogues, we have optimized an operationally simple electrochemical oxidative decarboxylation-nucleophilic addition pathway which exploits the reactivity of native C-terminal peptide carboxylates and abrogates the need for building block syntheses. Electrochemically-generated ,-acetal intermediates are engaged with electron-rich aromatics and organometallic reagents to forge modified amino acids and peptides. The value of this late-stage modification method is highlighted by the expedient and divergent production of bioactive peptide analogues, including compounds which exhibit enhanced cytotoxicity relative to the biseokeaniamide natural products.

Citing Articles

Electrochemically Enabled Total Syntheses of Natural Products.

Hatch C, Chain W ChemElectroChem. 2023; 10(11).

PMID: 38106361 PMC: 10723087. DOI: 10.1002/celc.202300140.

Electrochemical Late-Stage Functionalization.

Wang Y, Dana S, Long H, Xu Y, Li Y, Kaplaneris N Chem Rev. 2023; 123(19):11269-11335.

PMID: 37751573 PMC: 10571048. DOI: 10.1021/acs.chemrev.3c00158.

Tunable Electrochemical Peptide Modifications: Unlocking New Levels of Orthogonality for Side-Chain Functionalization.

Karipal Padinjare Veedu D, Connal L, Malins L Angew Chem Int Ed Engl. 2022; 62(4):e202215470.

PMID: 36336657 PMC: 10107541. DOI: 10.1002/anie.202215470.

Electrochemically Mediated Oxidation of Sensitive Propargylic Benzylic Alcohols.

Hatch C, Martin M, Gilmartin P, Xiong L, Beam D, Yap G Org Lett. 2022; 24(7):1423-1428.

PMID: 35148118 PMC: 9097598. DOI: 10.1021/acs.orglett.1c03860.

Cu-catalyzed asymmetric addition of alcohols to β,γ-alkynyl-α-imino esters for the construction of linear chiral N,O-ketals.

Sheng C, Ling Z, Luo Y, Zhang W Nat Commun. 2022; 13(1):400.

PMID: 35058446 PMC: 8776757. DOI: 10.1038/s41467-022-28002-7.

References

Orjala J, Gerwick W . Barbamide, a chlorinated metabolite with molluscicidal activity from the Caribbean cyanobacterium Lyngbya majuscula. J Nat Prod. 1996; 59(4):427-30. DOI: 10.1021/np960085a. View

Wiebe A, Gieshoff T, Mohle S, Rodrigo E, Zirbes M, Waldvogel S . Electrifying Organic Synthesis. Angew Chem Int Ed Engl. 2018; 57(20):5594-5619. PMC: 5969240. DOI: 10.1002/anie.201711060. View

Sharma S, Schiller M . The carboxy-terminus, a key regulator of protein function. Crit Rev Biochem Mol Biol. 2019; 54(2):85-102. PMC: 6568268. DOI: 10.1080/10409238.2019.1586828. View

Bottecchia C, Noel T . Photocatalytic Modification of Amino Acids, Peptides, and Proteins. Chemistry. 2018; 25(1):26-42. PMC: 6348373. DOI: 10.1002/chem.201803074. View

Yan M, Kawamata Y, Baran P . Synthetic Organic Electrochemical Methods Since 2000: On the Verge of a Renaissance. Chem Rev. 2017; 117(21):13230-13319. PMC: 5786875. DOI: 10.1021/acs.chemrev.7b00397. View

Mohle S, Zirbes M, Rodrigo E, Gieshoff T, Wiebe A, Waldvogel S . Modern Electrochemical Aspects for the Synthesis of Value-Added Organic Products. Angew Chem Int Ed Engl. 2018; 57(21):6018-6041. PMC: 6001547. DOI: 10.1002/anie.201712732. View

Yamada T, Yagita M, Kobayashi Y, Sennari G, Shimamura H, Matsui H . Synthesis and Evaluation of Antibacterial Activity of Bottromycins. J Org Chem. 2018; 83(13):7135-7149. DOI: 10.1021/acs.joc.8b00045. View

Dang T, Sussmuth R . Bioactive Peptide Natural Products as Lead Structures for Medicinal Use. Acc Chem Res. 2017; 50(7):1566-1576. DOI: 10.1021/acs.accounts.7b00159. View

Subiros-Funosas R, Prohens R, Barbas R, El-Faham A, Albericio F . Oxyma: an efficient additive for peptide synthesis to replace the benzotriazole-based HOBt and HOAt with a lower risk of explosion. Chemistry. 2009; 15(37):9394-403. DOI: 10.1002/chem.200900614. View

10.

Sun H, Moeller K . Silyl-substituted amino acids: new routes to the construction of selectively functionalized peptidomimetics. Org Lett. 2002; 4(9):1547-50. DOI: 10.1021/ol025776e. View

11.

deGruyter J, Malins L, Baran P . Residue-Specific Peptide Modification: A Chemist's Guide. Biochemistry. 2017; 56(30):3863-3873. PMC: 5792174. DOI: 10.1021/acs.biochem.7b00536. View

12.

Chang Z, Flatt P, Gerwick W, Nguyen V, Willis C, Sherman D . The barbamide biosynthetic gene cluster: a novel marine cyanobacterial system of mixed polyketide synthase (PKS)-non-ribosomal peptide synthetase (NRPS) origin involving an unusual trichloroleucyl starter unit. Gene. 2002; 296(1-2):235-47. DOI: 10.1016/s0378-1119(02)00860-0. View

13.

deGruyter J, Malins L, Wimmer L, Clay K, Lopez-Ogalla J, Qin T . CITU: A Peptide and Decarboxylative Coupling Reagent. Org Lett. 2017; 19(22):6196-6199. PMC: 5792187. DOI: 10.1021/acs.orglett.7b03121. View

14.

Wang W, Lorion M, Shah J, Kapdi A, Ackermann L . Late-Stage Peptide Diversification by Position-Selective C-H Activation. Angew Chem Int Ed Engl. 2018; 57(45):14700-14717. DOI: 10.1002/anie.201806250. View

15.

Horn E, Rosen B, Baran P . Synthetic Organic Electrochemistry: An Enabling and Innately Sustainable Method. ACS Cent Sci. 2016; 2(5):302-8. PMC: 4882743. DOI: 10.1021/acscentsci.6b00091. View

16.

Patra T, Maiti D . Decarboxylation as the Key Step in C-C Bond-Forming Reactions. Chemistry. 2016; 23(31):7382-7401. DOI: 10.1002/chem.201604496. View

17.

Carroll A, Feng Y, Bowden B, Coll J . Studies of Australian Ascidians. 5. Virenamides A-C, New Cytotoxic Linear Peptides from the Colonial Didemnid Ascidian Diplosoma virens. J Org Chem. 1996; 61(12):4059-4061. DOI: 10.1021/jo951379o. View

18.

Luesch H, Yoshida W, Moore R, Paul V . Apramides A-G, novel lipopeptides from the marine cyanobacterium Lyngbya majuscula. J Nat Prod. 2000; 63(8):1106-12. DOI: 10.1021/np000078t. View

19.

Ilardi E, Zakarian A . Efficient total synthesis of dysidenin, dysidin, and barbamide. Chem Asian J. 2011; 6(9):2260-3. DOI: 10.1002/asia.201100338. View

20.

Iwasaki A, Tadenuma T, Sumimoto S, Ohshiro T, Ozaki K, Kobayashi K . Biseokeaniamides A, B, and C, Sterol O-Acyltransferase Inhibitors from an Okeania sp. Marine Cyanobacterium. J Nat Prod. 2017; 80(4):1161-1166. DOI: 10.1021/acs.jnatprod.7b00137. View