Allobetulin

Round 1

Reviewer 1 Report

The manuscript describes a new practical procedure to carry out the Wagner-Meerwein rearrangement on betulin. Allobetulin is obtained in good yields with a simple procedure.

The manuscript is well written and deserves to be published basically in the present form.

I only have the two following minor points.

1.       I would name the reagent tetrafluoroboric acid dimethyl ether complex.

2.       I’m not terribly convinced about describing HBF₄ as a catalyst since it used in 66% amount with respect to betulin. Although it may be not practical on the scale authors describe in experimental part, do they have data using a truly catalytic amount?

Author Response

RESPONSE TO REFEREES – Reviewer 1

Thank you very much for your review. We are absolutely convinced that your comments and suggestions significantly improved the scientific value of our paper.

1. I would name the reagent tetrafluoroboric acid dimethyl ether complex.

We have changed the name according to the Reviewer's suggestion.

2. I’m not terribly convinced about describing HBF₄ as a catalyst since it used in 66% amount with respect to betulin. Although it may be not practical on the scale authors describe in experimental part, do they have data using a truly catalytic amount?

We agree with the Reviewer, therefore we have introduced appropriate changes to the text (we used the expression: “in the presence of tetrafluoroboric acid diethyl ether complex” – see lines: 13, 55, 124; see also track-changes version). Unfortunately, we have no data on reactions where less acid is added.

Kind regards

Mirosława Grymel

Jakub Adamek

Reviewer 2 Report

Authors reported alternative conditions to synthesize Allobetullin, through Wagner-Meerwein rearrangement using HBF4 as acid catalyst.

To improve the manuscript, the authors could address the following points:

- Lines 60-61, they mentioned that the final compound crystallizes. This is contradictory with the experimental procedure described in the Materials section, where the product precipitates as a white/pink solid, it was dried and slurry. This process seems incompatible with obtaining crystals as described, please correct one or the other/ or both.

- Line 59 and 106, the concept or washing hereby, could be confusing. It seems that the authors indeed, slurried the solid in acetone (where is insoluble) and then decanted the acetone solution with a pipette Pasteur.

- Please revise the text to reduce English mistakes, e.g., "..., often uncontrolled, ...(missing comma Line 19)

In general, I recommend the manuscript for publication, but I strongly recommend Grymel et al. to clear up the confusing part regarding the purification.

Author Response

RESPONSE TO REFEREES – Reviewer 2

Thank you very much for your review. We are absolutely convinced that your additional comments significantly improved the scientific value of our paper.

- Lines 60-61, they mentioned that the final compound crystallizes. This is contradictory with the experimental procedure described in the Materials section, where the product precipitates as a white/pink solid, it was dried and slurry. This process seems incompatible with obtaining crystals as described, please correct one or the other/ or both.

We agree with the Reviewer - the purification part was confusing, therefore we have introduced appropriate changes to the text (see lines: 60-62; see also track-changes version).

- Line 59 and 106, the concept or washing hereby, could be confusing. It seems that the authors indeed, slurried the solid in acetone (where is insoluble) and then decanted the acetone solution with a pipette Pasteur.

We agree with the Reviewer. Thank you for the suggestion – the procedure is more clear/understandable now. We have introduced appropriate changes to the text (see lines: 60-62, and 107-110; see also track-changes version).

- Please revise the text to reduce English mistakes, e.g., "..., often uncontrolled, ...(missing comma Line 19).

We read the text more carefully and corrected the mistakes we found (see track-changes version).

Best regards,

Mirosława Grymel

Jakub Adamek