Steglich esterification: A versatile synthetic approach toward the synthesis of natural products, their analogues/derivatives

Munawar, Saba; Zahoor, Ameer Fawad; Hussain, Syed Makhdoom; Ahmad, Sajjad; Mansha, Asim; Parveen, Bushra; Ali, Kulsoom Ghulam; Irfan, Ahmad

doi:10.1016/j.heliyon.2023.e23416

Cited by 16 publications

(4 citation statements)

References 100 publications

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“…Unfortunately, only microcrystalline materials were observed and from only a limited number of ENaCt experiments (see Supporting Information). The introduction of brominated aromatic moieties into natural products is known to increase both crystallinity, through introduced intramolecular π-stacking interactions, and anomalous X-ray scattering, to assist in determination of absolute configuration. − Thus, taking advantage of the carboxylic acid moiety in wheldone, a Steglich-type − reaction was carried out using p -bromobenzylamine in dichloromethane with DCC and DMAP, leading to the formation of the wheldone p -bromobenzylamide derivative. , HRESIMS analysis helped to establish the molecular formula of this derivative as C 32 H 40 O 5 NBr ( m / z 598.2150, [M + H] + ), which corresponded to an index of hydrogen deficiency of 13 and was consistent with the addition of a phenyl. Two doublets at δ H 7.22 ( J = 8.10 Hz, 2H) and δ H 7.47 ( J = 8.10 Hz, 2H), characteristic of a 1,4-disubstituted benzene, a singlet signal of a methylene at δ H /δ C 4.41/43.6 ppm, and an amide carbonyl at δ C 168.1, as well as HMBC correlations from δ H 7.33/5.87/4.41 to δ C 168.1 ppm, confirmed the position of the p -bromobenzylamide moiety (Table S8, Figures S18–S23).…”

Section: Resultsmentioning

confidence: 99%

Wheldone Revisited: Structure Revision Via DFT-GIAO Chemical Shift Calculations, 1,1-HD-ADEQUATE NMR Spectroscopy, and X-ray Crystallography Studies

Rangel-Grimaldo,

Earp,

Raja

et al. 2024

J. Nat. Prod.

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Wheldone is a fungal metabolite isolated from the coculture of Aspergillus f ischeri and Xylaria f labelliformis, displaying cytotoxic activity against breast, melanoma, and ovarian cancer cell lines. Initially, its structure was characterized as an unusual 5-methylbicyclo[5.4.0]undeca-3,5-diene scaffold with a 2-hydroxy-1-propanone side chain and a 3-(2-(1-hydroxyethyl)-2-methyl-2,5-dihydrofuran-3-yl)acrylic acid moiety. Upon further examination, minor inconsistencies in the data suggested the need for the structure to be revisited. Thus, the structure of wheldone has been revised using an orthogonal experimental-computational approach, which combines 1,1-HD-ADEQUATE NMR experiments, DFT-GIAO chemical shift calculations, and single-crystal X-ray diffraction (SCXRD) analysis of a semisynthetic p-bromobenzylamide derivative, formed via a Steglich-type reaction. The summation of these data now permits the unequivocal assignment of both the structure and absolute configuration of the natural product.

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Section: Resultsmentioning

confidence: 99%

Wheldone Revisited: Structure Revision Via DFT-GIAO Chemical Shift Calculations, 1,1-HD-ADEQUATE NMR Spectroscopy, and X-ray Crystallography Studies

Rangel-Grimaldo,

Earp,

Raja

et al. 2024

J. Nat. Prod.

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“…A number of conditions (Figure c) have been screened at this stage using alcohol 8 . Steglich and its modified versions (entries 1–4) furnished ester 15 in 58–78% yield, whereas Shiina − (entry 5), Yamaguchi − (entry 6), and Trost , (entry 7) conditions resulted it in 75%, 63%, and 50% yield, respectively. Next, ester 15 was subjected to Fmoc deprotection and the resultant amine was coupled with the corresponding acid prepared from dipeptide 10 in the presence of HATU/HOAt/DIPEA to obtain compound 6 (Route A).…”

Section: Resultsmentioning

confidence: 99%

Total Synthesis of Lipopeptide Bacilotetrin C: Discovery of Potent Anticancer Congeners Promoting Autophagy

Auddy,

Gupta,

Mandi

et al. 2024

ACS Med. Chem. Lett.

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A convergent strategy for the first total synthesis of the lipopeptide bacilotetrin C has been developed. The key features of this synthesis include Crimmins acetate aldol, Steglich esterification, and macrolactamization. Twenty-nine variants of the natural product were prepared following a systematic structure−activity relationship study, where some of the designed analogues showed promising cytotoxic effects against multiple human carcinoma cell lines. The most potent analogue exhibited a ∼37-fold enhancement in cytotoxicity compared to bacilotetrin C in a triple-negative breast cancer (MDA-MB-231) cell line at submicromolar doses. The study further revealed that some of the analogues induced autophagy in cancer cells to the point of their demise at doses much lower than those of known autophagy-inducing peptides. The results demonstrated that the chemical synthesis of bacilotetrin C with suitable improvisation plays an important role in the development of novel anticancer chemotherapeutics, which would allow future rational design of novel autophagy inducers on this template.

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“…In the synthesis of cyclohexyl derivatives of coumarins (CRM 1-4), we employed the Steglich esterification which is a more efficient and mild alternative to traditional esterification methods, Scheme 1 [41,42]. The substrate used in the esterification reaction, coumarin-3-carboxylic acid (1), was synthesized from Meldrum's acid and salicylaldehyde.…”

Section: Synthesis Of Coumarinsmentioning

confidence: 99%

Coumarin Derivatives: The Influence of Cycloalkyl Groups at the C-3 Position on Intermolecular Interactions—Synthesis, Structure and Spectroscopy

Szwaczko,

Kamiński,

Koziol

2024

Crystals

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In this study, we explore the synthesis and solid-state characterization of four coumarin-3-carboxylic acid esters, each modified at the C-3 position with different cycloalkyl groups: cyclohexyl, menthyl, and iso-pulegyl. We conducted a detailed analysis of these compounds utilizing a variety of techniques such as a single-crystal X-ray diffraction, nuclear magnetic resonance (NMR), and Fourier-transform infrared (FTIR) spectroscopy. Additionally, we calculated the dipole moments for these molecules. Our findings include a thorough structural assessment, highlighting the role of noncovalent interactions through Full Interaction Maps and Hirshfeld surface analysis. This study reveals the critical influence of the weak C-H…O hydrogen bonds in determining the solid-state architecture of these esters, whereas π-π stacking interactions appear to be negligible among the studied derivatives.

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Steglich esterification: A versatile synthetic approach toward the synthesis of natural products, their analogues/derivatives

Cited by 16 publications

References 100 publications

Wheldone Revisited: Structure Revision Via DFT-GIAO Chemical Shift Calculations, 1,1-HD-ADEQUATE NMR Spectroscopy, and X-ray Crystallography Studies

Wheldone Revisited: Structure Revision Via DFT-GIAO Chemical Shift Calculations, 1,1-HD-ADEQUATE NMR Spectroscopy, and X-ray Crystallography Studies

Total Synthesis of Lipopeptide Bacilotetrin C: Discovery of Potent Anticancer Congeners Promoting Autophagy

Coumarin Derivatives: The Influence of Cycloalkyl Groups at the C-3 Position on Intermolecular Interactions—Synthesis, Structure and Spectroscopy

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