4-Methoxyphenethyl (E)-3-(o-tolyl)acrylate

Round 1

Reviewer 1 Report

The presented short note concerns the method of synthesizing one derivative, we do not know whether the obtained results are reproducible in the case of other reagents, it is worth supplementing the research with further analogues. The conclusions presented are not exhaustive: it is not known if the process was repeated to improve efficiency. The results of spectroscopic tests included in the additional materials should be supplemented with the full original H NMR spectrum (complete, uncorrected), provided with the structural formula of the tested molecule. Interpretation of FR-IR spectroscopy should be completed with signals derived from the ortho-tolyl substituent. Mass spectroscopy reveals the presence of many other substrate signals, intermediates, or by-products, and indicates insufficient purification of the final product, which may have a direct impact on the potential biological effects described herein. The liquid form of the final product may justify the inability to perform elemental analysis, but it may also indicate a significant contamination of the sample (Rf is not given for the substrates and the final product monitored by TLC). Explain these issues, describe the chromatographic purification process, check that the end product is sufficiently homogeneous for further testing of biological activity. This question can be answered by an image of NMR spectroscopy over the full frequency range, where only the desired signals of the expected proton groups will be visible. The molecular docking process is briefly discussed, and no computational data is provided in the supporting material. Complete the information: InChI  and summary formula.

Author Response

The presented short note concerns the method of synthesizing one derivative, we do not know whether the obtained results are reproducible in the case of other reagents, it is worth supplementing the research with further analogues. The conclusions presented are not exhaustive: it is not known if the process was repeated to improve efficiency.

response:

Short note in MolBank generally report synthesis of single compound. We are now preparing further analogues for next publication.

The results of spectroscopic tests included in the additional materials should be supplemented with the full original H NMR spectrum (complete, uncorrected), provided with the structural formula of the tested molecule.

response:

We have submitted Supplementary Materials together with the manuscript.

Interpretation of FR-IR spectroscopy should be completed with signals derived from the ortho-tolyl substituent.

response:

We have fixed the manuscript.

Mass spectroscopy reveals the presence of many other substrate signals, intermediates, or by-products, and indicates insufficient purification of the final product, which may have a direct impact on the potential biological effects described herein. The liquid form of the final product may justify the inability to perform elemental analysis, but it may also indicate a significant contamination of the sample (Rf is not given for the substrates and the final product monitored by TLC).

response:

We have made sure to use pure compound as seen in the NMR. We have also characterized the compounds using HRMS.

Explain these issues, describe the chromatographic purification process, check that the end product is sufficiently homogeneous for further testing of biological activity.  This question can be answered by an image of NMR spectroscopy over the full frequency range, where only the desired signals of the expected proton groups will be visible.

response:

We have submitted the NMR spectra in Supplementary Materials together with the manuscript.

The molecular docking process is briefly discussed, and no computational data is provided in the supporting material. Complete the information: InChI and summary formula.

Response:

We have detailed the molecular docking process in the manuscript and have included the computational data in the supporting material.

Reviewer 2 Report

In the manuscript entitled “4-Methoxyphenethyl (E)-3-(o-tolyl)acrylate”, Santoso et al. describe the synthesis, the characterization and the biological evaluation as α-glucosidase inhibitor of 4-methoxyphenethyl (E)-3-(o-tolyl)acrylate. The synthetic procedure for the preparation of the title compound is well described and the IR, NMR and MS spectra reported in the supporting material prove the identity and the purity of the obtained product (a HPLC analysis could also be included).

For these reasons I think that the manuscript is suitable to be published in Molbank

Some minor concerns are listed below:

-          Lines 26-27 the authors state “Hydroxybenzotriazole (HOBt) can be used as coupling agent to synthesize esters [28,36]”. Nevertheless, HOBt is not a coupling reagent but it is usually added to other coupling reagents such as EDC (as in the case of ref. 28 and 36) or HBTU (that is commonly used in peptides synthesis) to fasten reaction time and increase the yield.

-          4-Methoxyphenethyl (E)-3-(o-tolyl)acrylate was obtained in 51% yield. I wonder if the authors have any explanation for this non optimal yield. Have the authors tried different reaction conditions (solvent, temperature, reaction time) to improve it?

-          Line 54 and line 114, “α-. Glucosidase” should be “α-Glucosidase”

-          Line 111: “3.42” should be 34.42

Author Response

In the manuscript entitled “4-Methoxyphenethyl (E)-3-(o-tolyl)acrylate”, Santoso et al. describe the synthesis, the characterization and the biological evaluation as α-glucosidase inhibitor of 4-methoxyphenethyl (E)-3-(o-tolyl)acrylate. The synthetic procedure for the preparation of the title compound is well described and the IR, NMR and MS spectra reported in the supporting material prove the identity and the purity of the obtained product (a HPLC analysis could also be included).

Response:

Many thanks for positive response.

For these reasons I think that the manuscript is suitable to be published in Molbank. Some minor concerns are listed below:

-          Lines 26-27 the authors state “Hydroxybenzotriazole (HOBt) can be used as coupling agent to synthesize esters [28,36]”. Nevertheless, HOBt is not a coupling reagent but it is usually added to other coupling reagents such as EDC (as in the case of ref. 28 and 36) or HBTU (that is commonly used in peptides synthesis) to fasten reaction time and increase the yield.

Response:

We have fixed the manuscript.

-          4-Methoxyphenethyl (E)-3-(o-tolyl)acrylate was obtained in 51% yield. I wonder if the authors have any explanation for this non optimal yield. Have the authors tried different reaction conditions (solvent, temperature, reaction time) to improve it?

Response:

We have faced some problems during purification. The yield given is the very pure fraction, we were not able to purify the rest to an acceptable level. However we are also preparing further analogues.

-          Line 54 and line 114, “α-. Glucosidase” should be “α-Glucosidase”

Response:

We have fixed the manuscript.

-          Line 111: “3.42” should be 34.42

Response:

We have fixed the manuscript.

Round 2

Reviewer 1 Report

The explanations provided by the authors are satisfactory, and I recommend publishing them in their present form