Briarenones A‒C, New Briarellin Diterpenoids from the Gorgonian Briareum violaceum

Due to the low quality of   Figures presented in Supplementary, I   am not able to review this manuscript. The Figures are unreadable when   printed and of very low quality (pixel   form) when presented on a computer   screen, even after zoom.

We have replaced the low-resolution   ¹H NMR, ¹³CNMR spectra by the high-resolution version. DEPT spectra of the   three compounds were also added.

There is a lack of Figure S10   (13C NMR spectrum for the compound 2). In Figures S2 and S9 (1H NMR for the   compounds 1 and 2), the chemical shifts of majority signals are not   presented. Therefore, I am not able to compare the information presented in   the main text and in Table 1 and in the Figures in Supplementary.

The ¹³C NMR spectrum for the compound 2 (Figure   S12) is now included (in detailed sections) along with the DEPT spectra   (Figure S13). Moreover, the ¹H NMR spectrum of each compound is divided into low and high field regions for better reading of the ¹H   signal splitting pattern and chemical shifts.   

Additionally, there is a difference in some decimal places between the   chemical shift in Tables 1 and in the   spectra, which makes review tedious. I suppose that the X-ray data help to   assign properly the NMR signals and to   determine the structures. However, it must be clearly presented.

Chemical shifts in Tables 1 were   revised to be matched with those in the spectra (the decimal places of ¹³C   NMR chemical shifts were also adjusted).

Also, we think that the NMR data for compounds of this type are sufficient for us to elucidate   the chemical structures. X-ray data were used to confirm the structures elucidated   by NMR and other spectroscopic data.

The work is thorough, well performed and described with only minor   English corrections suggested (see below). I would   like to see the mixing times for the NOESY experiments included in the   supplementary material.

We thank the reviewer for revising the manuscript and for the kind suggestions and comments. Mixing times for the ROESY and   NOESY experiments are 200 and 300 msec,   respectively. But, we corrected L158 and L243 with a slightly   different way.

line 21   replace "compounds with "the compounds."

line 38   replace "have been originally discovered" with "were   originally isolated."

line 85   replace "HMBC" with "the HMBC"

line 99   replace "has been " with "was"

line 110   and 126 replace "molecule" with "molecular"

line 122   replace "NOE" with "an NOE"

line 127   replace "for " with "of"

line 158   replace "This" with "These"

line 192   replace "frozen-dried" with "freeze-dried"

line 192   replace ", filtered" with "and filtered"

line 193   replace "over" with "by"

line 219   replace "for the analysis" with "were used for the analysis"

line 242   remove italic formatting on "inhabiting"

line 243   replace "This" with "These"

All indicated   corrections and suggested replacements have been followed.

This work is good-presented   example of classical NPC study. In general, it may be recommended for   publication in Marine Drugs, but after the revision. I'm not absolutely sure about suggested   configurations of 6-OH in 2 and 5-OH in 3 and think that this stereocentres should be checked   (verified) using strong proofs (e.g.   Mosher's method). These evidences can highly improve the manuscript quality. As I   understand, amounts of isolated compounds are enough for such study

We have revised this part to further validate the configurations of   6-OH in 2 and 5-OH in 3 as illustrated in the manuscript. This was achieved and supported by   comparison of the NMR chemical shifts of C-6, C-7, and H-6 of 2 with   those of allied eunicellin-derived compounds (Figure 4) and/or by a molecular   modeling study. We thought that all the information could   establish the structure of 2.

Previously, due to   low quality of Figures presented in Supplementary I was not able to review   this manuscript. The corrected version contains some improvement. According   to my remarks, the 13 NMR spectrum for the compound 2 was added. Data   presented in Table 1 was corrected. However, Figures S2 and S9 (1H NMR for   the compounds 1 and 2) were not improved. The chemical shifts of majority   signals are not presented. Therefore, it is still difficult to check   information based on which, the conclusion are drawn. The quality of Figures   in Supplementary are still low. The improvement is really simple, so it is   difficult to understand to me why it was not done. 

However,   despite of these difficulties, in my opinion, the structure determination is   correct, therefore, the manuscript can be accepted

We have replaced the low quality   ¹H NMR spectra of compound 1 and 2 in Figures S2 and   S10 by the high quality version. However, the detailed chemical shifts of   each spectrum are illustrated in two sections in Figures S3 and S11,   respectively.

The revised manuscript is   satisfactory.

We thank the reviewer for his kind evaluation and judgment.