Synthesis of a New Bichalcone via Suzuki–Miyaura Coupling Reaction

Round 1

Reviewer 1 Report

Comments and Suggestions for Authors

Comments

The manuscript entitled "Synthesis of a new bichalcone via Suzuki-Miyaura coupling reaction" describes the synthesis of a novel bichalcone 3’,3’’’,4,4’,4’’,4’’’,5’,5’’’-octamethoxy-2,3’’- bichalcone. The work is well presented and can be accepted after the following revisions:

1. In line 13, the phrase “an original bichalcone” should be revised to “a novel bichalcone”
2. In Section 3.1, the authors mention the use of 2D NMR, but no such data is provided or discussed. This reference should be removed unless the corresponding data is included.
3. In Figure 2, the title compound is labeled as 6, even though compounds 1–5 have not yet been introduced. Since it is the focus of the study and appears early in the manuscript, it would be clearer and more logical to assign it as compound 1.
4. In lines 85 and 93, the word “assay” is used to describe synthetic experiments. This term is more appropriate for biological studies. Please consider replacing it with “experiment,” “reaction,” or “trial.”
5. The authors selected THF as the solvent for the Suzuki–Miyaura coupling but did not mention whether other solvents (e.g., toluene, DMSO, DMF) were screened. Including a brief justification for choosing THF would strengthen the methodology section.
6. The use of 0.2 equivalents of palladium catalyst is quite high and raises concerns about economic viability for scale-up. It would be helpful if the authors could justify this choice or comment on efforts to optimize catalyst loading.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf

Reviewer 2 Report

Comments and Suggestions for Authors

This manauscript describes an efficient new synthetic methodology for bichalcones. The molecules synthesized in this work belong to the B-B (biaryl 206) type, which has a C-C bond and is uncommon in natural or synthetic bichalcones. This synthetic methodology could be used to synthesize various original bichalcones to further investigate their anti-cancer activity. Some of the product structures have been confirmed by NMR mapping. Overall, the manuscript is well structured and informative. However, some minor revisions need to be made before publication. The revisions are summarized.

1. In the introduction, the author elaborates on the excellent biological activity of bichalcones in detail, but lacks an introduction to the Suzuki-Miyaura reaction and its synthetic application in aryl coupling reactions.
2. On the first page, in line 16, the first letter of "bichalcones" needs to be capitalized.
3. Figure 2: It is suggested that the author mark the A ring and B ring described in the article in this figure.
4. On line 135 of page 5 of the article, “1.2.10^-3 mol” should be changed to “1.2×10⁻³ mol”. The same issue remains in the following text. It is suggested that the author carefully check it.
5. Table 1: The third and fourth items of optimizing the reaction conditions shown in this graph not only change the reaction time but also increase the equivalent of compound 3, which does not meet the requirements of the control variable method.

Author Response

Please see the attachment.

Author Response File: Author Response.pdf