New Derivatives of Lupeol and Their Biological Activity
Round 1
Reviewer 1 Report
The present contribution by Hoang-Thuy-Tien Le et al. reports the synthesis of three new lupeol derivatives and the evaluation of their biological potential as α-glucosidase inhibitors. In my opinion, the chemical part of the work is prepared very well. I have only a few comments / concerns which I addressed to the authors.
The first is about 13CNMR spectra of compound 2a and 2b. On those spectra can be seen an additional signal at 22.7 ppm. Do the authors consider this as a signal from the residual solvent?
It seems to me that the chemical shift of C-29 (compound 2a and 2b) was determined by the HMBC correlation. It would be useful to present a slightly larger part of the HMBC spectrum because the correlation between H-20 and C-29 cannot be seen in Figures S4 and S8.
Lines 135 and 136 according to 1HNMR the signals at 3.19 ppm can be assigned to the H-3 and the signal at 2.87 can be assigned to H-19.
There are some small misdescriptions in the main manuscript:
Line 68: “ortho-coupled protons at δH 7.51 and 7.46” I suggest correction to: ortho-coupled protons at δH 7.51 and 7.42
Lines 68-69: “trans double bond at δH 6.75 and 6.75” I suggest correction to: trans double bond at δH 6.75 and 7.46
It would also be helpful to describe in detail the procedure for aldol condensation (solvent used and basic or acid reactions conditions).
Overall, this is a nice work that has been thoroughly researched, with elements of novelty and significance complementing previous findings in this area. Thus, publication is recommended after minor revision of the proposed points.
Author Response
Please see the attachment.
Author Response File: 
Author Response.pdf
Reviewer 2 Report
In MS, the natural product lupeol (1) was oxidized into three new derivatives 2a, 2b, and 2, which was further converted to 3 by aldolization. Their chemical structures were partially elucidated by spectroscopic analyses (HRESIMS and NMR). Compounds 3 showed significant α-glucosidase inhibition with IC50 value of 202 μM while 2a and 2b were inactive. However, it is very strange how the reaction would generate products 2a and 2b in the absence of formic acid in the reaction system. Thus, this reviewer cannot recommend to publish it in current case.
Comments
1. Both products 2a and 2b are solid, please conduct single crystal XRD analysis to verify their structures before publication.
2. There are some problems in HRMS data. For 2a, HRESIMS calcd C36H52BrO2 ([M+Na]+): 523.3732 There is no Na in the molecular formula. Please check again. 2b has the same problem.
Author Response
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Author Response File: Author Response.pdf
Reviewer 3 Report
In the manuscript (molbank-1489494) authors describe the synthesis of three new lupeol derivatives, their chemical characterization by NMR and HRESIMS methods and their activity for a-glucosidase inhibition using suitable bioassays. Globally, the article is well-written and only minor issues should be addressed prior to its publication. Both spectroscopic methods are carefully designed and conducted and the results are also rationally explained and presented in the manuscript.
Minor issues:
- Page 1, line 29: “come with several serious complications.” Authors should be more explicit here providing also a citation.
- Authors should number the atoms in Figure 1 or move relative figures from supplementary to the manuscript in order to facilitate the readers to follow the text.
Author Response
Please see the attachment.
Author Response File: Author Response.pdf
Reviewer 4 Report
The presented article, although small in terms of the amount of research done, is of practical importance. New compounds are characterized quite correctly. I recommend the material for publication.
