Total synthesis of cyclohexadepsipeptides exumolides A and B

Rahmadani, Agung; Masruhim, Muhammad Amir; Rijai, Laode; Hidayat, Ace Tatang; Supratman, Unang; Maharani, Rani

doi:10.1016/j.tet.2021.131987

Cited by 10 publications

(18 citation statements)

References 10 publications

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“…This α‐hydroxy acid was successfully synthesised (81 % yield) but the synthesis strategy was slightly different from the previous study by Rahim et al. (2020) as the hydroxy group was not protected [48] …”

Section: Chemical Synthesis Of Precursor Cyclodepsipeptidesmentioning

confidence: 75%

Section: Chemical Synthesis Of Precursor Cyclodepsipeptidesmentioning

confidence: 99%

Section: Chemical Synthesis Of Precursor Cyclodepsipeptidesmentioning

confidence: 99%

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An Overview of the Synthesis of Biologically Active Cyclodepsipeptides

et al. 2022

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Cyclodepsipeptide are a class of natural cyclic peptides that have a wide range of biological activities, hence the potential to be developed as new drug candidates. Cyclodpesipeptides comprise a backbone of amide bonds and at least one ester moiety, thus are complex and challenging to synthesis. Generally, cyclodepsipeptides are synthesised via solid‐phase peptide synthesis, solution‐phase or a combination of solid and solution‐phase. Currently, solid‐phase peptide synthesis is more in demand, but it also has several challenges in its application especially for the cyclodepsipeptide that contains N‐methylated residues, as well as solution‐phase peptide synthesis tends to have a longer reaction step. Therefore, the combination of solid and solution‐phase peptide synthesis is a better alternative. This review discusses the synthetic strategies for cyclodepsipeptides including the preparation of precursor and macrocyclization.

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Section: Chemical Synthesis Of Precursor Cyclodepsipeptidesmentioning

confidence: 75%

Section: Chemical Synthesis Of Precursor Cyclodepsipeptidesmentioning

confidence: 99%

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An Overview of the Synthesis of Biologically Active Cyclodepsipeptides

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“…Solid‐phase peptide synthesis (SPPS) introduced by Merrifield in 1963 is known to be a faster method to prepare the linear precursor, compared to solution‐phase method. This method has been employed to synthesize several cyclopeptide such as nocardiamide, [5] petriellin A, [6] [2 S ,3 S ‐Hmp]‐aureobasidin L, [7] exumolides A, [8] and many more. The SPPS method was applied to synthesize the linear precursor of nocardiotide A, while cyclization in solution phase was chosen to provide the cyclic product.…”

Section: Introductionmentioning

confidence: 99%

Total Synthesis of Nocardiotide A by Using a Combination of Solid‐ and Solution‐Phase Methods

et al. 2021

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Nocardiotide A has been successfully synthesized using a combination of solid‐ and solution‐phase synthesis. Peptides 1 and 2 of nocardiotide A, with different C and N termini, were synthesized on 2‐chlorotrityl chloride resin. A combination of N,N,N′,N′‐tetramethyl‐O‐(1H‐benzotriazol‐1‐yl)uronium hexafluorophosphate and hydroxybenzotriazole (HBTU/HOBt) was employed as coupling reagent and the release of the linear peptides from the resin was undertaken using AcOH and trifluoroethanol (TFE) reagents resulting in linear hexapeptides with protected side chains in good yields (83.4 % and 76 %, respectively). Peptide 1, which has Ala as C terminus and Trp as N terminus, was the only peptide that was successfully cyclized without epimerization under a dilute condition (1.25×10−3 M) using HBTU (3 equiv.) and 1 % N,N‐diisopropylethylamine (DIPEA) in dichloromethane. A combination of a small residue at the C terminus and a larger residue at the N terminus was found to be effective for the cyclization. The protecting group of the crude cyclic product was then deprotected by 95 % TFA in water and the crude was then purified to give white solid product with 16 % overall yield. The peptide was then characterized by HR‐ToFMS, 1H‐ and 13C‐NMR spectroscopy. In order to ensure the absence of epimerization during cyclization, the D‐analogue of nocardiotide A was synthesized using similar synthetic protocol. The NMR data of D‐analogue was found to have a larger difference compared to the synthetic and natural product, showing there is no epimerization at C‐terminus during cyclization.

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“…The solid‐phase synthesis method is used to produce linear peptides and then followed by solution‐phase synthesis to form cyclic peptides. This method has been successfully carried out to produce cyclic peptides such as exumolides A and B, [8] c‐PLAI, [9] and [2 S ,3 S ‐Hmp]‐aureobacidin L [10].…”

Section: Introductionmentioning

confidence: 99%

Total synthesis of xylapeptide B [Cyclo‐(L‐Leu‐L‐Pro‐N‐Me‐Phe‐L‐Val‐D‐Ala)]

Kurnia

Maharani

Hidayat

et al. 2021

Journal of Heterocyclic Chem

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Xylapeptide B is a cyclopentapeptide isolated from Xylaria sp. derived from the Chinese medicinal plant Sophora tonkinensis. Xylapeptide B was successfully synthesized by a combination of solid‐ and solution‐phase, using the Fmoc strategy, and 2‐chlorotrityl chloride resin. The coupling reagent used is a combination of HBTU/HOBt to assist in the formation of amide bonds. D‐Ala was chosen as the C‐terminal because it has a small residue and can facilitate the cyclization process. Linear peptide was cleaved from the resin using a dilute acid concentration of 20% TFA in DCM because the peptide has no protecting group at the side chain. Crude linear peptide was purified by semi‐preparative RP‐HPLC using 0%–100% ACN eluent for 35 min and obtained a pure mass of 22.4 mg (18.83%). Cyclization was carried out in solution phase using HBTU (3 eq.) and DIPEA (1% v/v) in diluted concentration (1.25 mM) for 72 h at room temperature. The cyclization stage was monitored by thin‐layer chromatography (TLC). Crude xylapeptide B was purified by semi‐preparative RP‐HPLC using 30%–80% ACN eluent for 40 min, to result in 6 mg (8.91%) of the desired xylapeptide B. All synthesized products were characterized by HR‐TOFMS, 1H‐, and 13C‐NMR.

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Total synthesis of cyclohexadepsipeptides exumolides A and B

Cited by 10 publications

References 10 publications

An Overview of the Synthesis of Biologically Active Cyclodepsipeptides

An Overview of the Synthesis of Biologically Active Cyclodepsipeptides

Total Synthesis of Nocardiotide A by Using a Combination of Solid‐ and Solution‐Phase Methods

Total synthesis of xylapeptide B [Cyclo‐(L‐Leu‐L‐Pro‐N‐Me‐Phe‐L‐Val‐D‐Ala)]

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