Preparation of Key Intermediates for the Syntheses of Coenzyme Q₁₀ and Derivatives by Cross-Metathesis Reactions

Round 1

Reviewer 1 Report

The manuscript entitled ‘Preparation of Key Intermediates for the Synthesis of Coenzyme Q10 and Derivatives by Cross-metathesis Reactions’

by Trang Nguyen, Hung Mac and Phong Pham

reports the synthesis, catalyzed by 2nd gen. Grubb’s catalyst, of five benzylmethacrylate esters from allylarenes and methylmethacrylate. Then, they carried out the reduction of some products to alcohols and reported one example of functionalization to give a derivative bearing a solanesyl moiety. The authors claim to have synthesized Coenzyme Q₁₀ (in the title) and derivatives, but did not performed the deprotection step to obtain Coenzyme Q₁₀.

The manuscript is not particularly innovative since other papers reported a similar approaches to obtain Coenzyme Q₁₀ and its derivatives. Moreover, a careful revision is needed prior to be considered for publication. Some points are as follows:

Deprotection of 10 to give quinol derivative must be done

In Scheme 1 the first structure must be indicated as quinol or hydroquinone, or benzene-1,4-diol

In Scheme 2 the numbering of compounds must be added

In Scheme 3, the first step to obtain compounds 5 require nirogen athmosfere: thi must be indicated

Table 1: footnotes b and c are the same

Scheme 4. Why only 6b, c, e have been subjected to reduction?

Experimental: Compounds derived from General procedure for allylation reaction must be numbered and the path used must be indicated

Page 5, refeences 1 and 2 are inserted as footnotes: references must numbered consecutively and inserted in the dedicated section.

Reference 12: the first part is a note, not a bibliography: it must be inserted in the main text.

Supportin information: many spectra indicated as 13C seem to be spectra obtained from DEPT experiments: ¹³C NMR spectra must be added.

Some other typos are present along the text (e.g: schem, inseperable, etc)

Author Response

Dear Reviewer:

            Thank you very much for your comments on our manuscript. We have fixed our manuscript as your detail suggestions as being presented in the following table.

Thank you again for your suggestion.

Your sincerely,

Phong Pham, Hung Mac, and Trang Nguyen

Reviewer 2 Report

Pham et al. describe a new approach for the synthesis of coenzyme Q10 and some other derivatives, there is not much to say about the MS but that the chemistry is sound and seem to have been performed in a proper manner with the conclusion reached in line with the results presented. I believe that a careful revision of the English grammar would certainly improve the MS. Once this query has been properly addressed, I believe the MS can be accepted for publication.

Author Response

Dear Reviewer:

            Thank you very much for your kindly support to our manuscript.

Your sincerely,

Phong Pham, Hung Mac, and Trang Nguyen

Reviewer 3 Report

The paper describes the preparation of key intermediates for the synthesis of coenzyme Q10 and derivatives by cross-metathesis reactions. The work is interesting, well performed and nicely described. The product characterization is adequate. The results are important to scientists in the field of synthetic chemistry.
I suggest that the paper is accepted after minor revisions.
Requested changes:
-The images in the schemes look fuzzy and of low quality. Please improve.
-In page 2, section ''design plan'' the authors mention compound numbers 2, 3 and 4 but those are not included in the following scheme which makes it confusing to the reader. Please add the compound numbering under each structure in scheme 2.
-The authors claim to have saved one synthetic step by starting from the methoxy ether of starting aryl bromide instead of the phenol. This is not really the case as the methoxy ether is probably a derivative of the phenol thereby the extra step exists but was performed by the industry. One needs to consider these details when claiming to improve important synthetic routes.
-Use of Stille coupling is best to be avoided due to the toxicity of stannyl reagents. Have the authors considered alternative Suzuki protocols?
-The structure of 2c in scheme 5 is rotated differently to all the previous schemes and table. This can be confusing to the reader. Please rotate all structures the same way.
Regarding the experimental:
-Compounds 4a, 4e and 2e are reported in the literature. Please add a reference to the literature proceedures in the experimental and compare your data to the ones reported. This should be done for all literature compounds.
-The authors need to report IR data for all new compounds.

Author Response

Dear Reviewer:

            Thank you very much for your kindly comments on our manuscript. We have fixed our manuscript as your detail suggestions as being presented in the following table.

Thank you again for your suggestion.

Your sincerely,

Phong Pham, Hung Mac, and Trang Nguyen

Round 2

Reviewer 1 Report

The manuscript, after the revision, is suitable for publication.