Synthesis of Homodrimane Sesquiterpenoids Bearing 1,3-Benzothiazole Unit and Their Antimicrobial Activity Evaluation
Round 1
Reviewer 1 Report
Although the manuscript by Aricu et al. involves some interesting results with full experimental data, it should not be accepted without major revision due to the following reason.
1. Reaction pathways in Schemes 2 and 5 are not reasonable.
2. This manuscript involves many wrong expressions in English and should be re-written with the aid of English editing service.
Please describe reaction temperature in Schemes 1, 3 and 4 instead of delta.
Please mention on the role of PPh3 in Scheme 2.
In Scheme 2, authors suggested initial formation of the amide. However, nucleophilicity of the nitrogen in aniline is not high enough to provide amide under the reaction conditions. Alternative pathway might be initial formation of thioester followed by the attack of the nitrogen lone pair to the carbonyl group. Please re-consider on the reaction pathway of benzothioimidazole synthesis.
In Scheme 5, departure of a hydride from the intermediate 28 is not reasonable under the reaction conditions. Abstraction of the hydrogen as a proton by a conjugate might be feasible.
In the intermediate 29, the upper arrow indicates intramolecular hydride attack to the olefin, which is not acceptable. The lower arrow indicates the attack of the nitrogen lone pair to the double bond, which is not reasonable. Activation of the double bond might be needed to allow such nucleophilic attack. Please re-consider.
Determination of the geometry of the C=N bond of compound 24 is needed.
The English in this manuscript should be revised and edited by a native speaker.
Lack of definite article “the” gives difficulty in catching the meaning of sentences.
Following corrections are suggested, though not sufficient corrections.
Authors should be careful to tense, plural etc.
27: compared –> compared to
63: 1 –> (1)
64: the same initial lactone –> sclrareoride (1),
64: delete “others intermediate”
65: delete “separate”
68: was –> were
71: depicted –> in the yields as depicted in the Scheme 1.
77: was –> were
77: signal –> signals
82: spectra pattern –> spectral data
83: instead –> in addition to
85: obtained –> afforded
86: spectra –> spectrum
87: initial –> starting
91: base –> basia
95: at –> according to
105: mechanism –> Reaction pathway
114: ditto
118: 1 –> (1)
123: contains –> involve
162: signal –> signals
164: of compound 23 –> –> of the structure of compound 24 by
173: in –> under
177: confirm –> confirmed
179: analysis –> structural analysis
179: of –> by
202: mechanism –> reaction pathway
204: first of all –> initial
205: delete “and led to obtained before amide”
213: reveal –> revealed
214: posses –> possessed
216: ditto
217: ditto
220: ditto
221: are –> were
244: remain –> residue
244: acidulated –> acidified
313: additionally –> subsequently
315: delete “obtained in situ”
316: delete “dissolved”
Author Response
Comments/suggestions: |
Answers/corrections: |
Reaction pathways in Schemes 2 and 5 are not reasonable. |
The reaction pathways were revised. The Scheme 5 was divided in Schemes 5 and 6, respectively. This is our vision on reaction mechanisms, based on our experience in the field. But we did not exclude other explications |
This manuscript involves many wrong expressions in English and should be re-written with the aid of English editing service. |
The manuscript was re-writen and edited by a specialist in the field. |
Please describe reaction temperature in Schemes 1, 3 and 4 instead of delta. |
The reaction temperatures were mentioned in Schemes 1, 3 and 4. |
Please mention on the role of PPh3 in Scheme 2. |
PPh3 promotes the condensation reaction between 2-aminothiophenol and carboxylic acids by formation of intermediate acylphosphonium intermediate. |
Determination of the geometry of the C=N bond of compound 24 is needed. |
Additional NOESY experiments confirmed the E- configuration of >C=N- double bond in molecule of compound 25 (former 24, the numbering was changed). |
The English in this manuscript should be revised and edited by a native speaker. |
The English was revised and edited. |
Line 27: compared –> compared to |
compared to |
Line 63: 1 –> (1) |
(1) |
Line 64: the same initial lactone –> sclareolide (1), |
sclareolide (1) |
Line 64: delete “others intermediate” |
Deleted |
Line 65: delete “separate” |
Deleted |
Line 68: was –> were |
Were |
Line 71: depicted –> in the yields as depicted in the Scheme 1. |
in the yields as depicted in the Scheme 1 |
Line 77: was –> were |
The formation.......were proved, |
Line 77: signal –> signals |
Signals |
Line 82: spectra pattern –> spectral data |
spectral data |
Line 83: instead –> in addition to |
in addition to |
Line 85: obtained –> afforded |
Afforded |
Line 86: spectra –> spectrum |
Spectrum |
Line 87: initial –> starting |
Starting |
Line 91: base –> basis |
Basis |
Line 95: at –> according to |
according to |
Line 105, 114: mechanism –> Reaction pathway |
reaction pathway |
Line 118: 1 –> (1) |
(1) |
Line 123: contains –> involve |
Involve |
Line 162: signal –> signals |
Signals |
Line 164: of compound 23 –> –> of the structure of compound 24 by |
of the structure of compound 25 by (former 24, the numbering was changed) |
Line 173: in –> under |
Under |
Line 177: confirm –> confirmed |
Confirmed |
Line 179: analysis –> structural analysis |
structural analysis |
Line 179: of –> by |
By |
Line 202: mechanism –> reaction pathway |
reaction pathway |
Line 204: first of all –> initial |
Initial |
Line 205: delete “and led to obtained before amide” |
Deleted |
Line 213: reveal –> revealed |
Revealed |
Lines 214, 216, 217, 220: posses –> possessed |
Possessed |
Line 221: are –> were |
Were |
Line 244: remain –> residue |
Residue |
Line 244: acidulated –> acidified |
Acidified |
Line 313: additionally –> subsequently |
Subsequently |
Line 315: delete “obtained in situ” |
Deleted |
Line 316: delete “dissolved” |
Deleted |
Reviewer 2 Report
The paper reports the synthesis of new sesquiterpenes for antimicrobial applications.
In general, the manuscript is relevant for the field. However, in the introduction section, the authors need to introduce some applications of the sesquiterpenoids for a better compensation.
On the results, the authors should explain in more detail the interrelation between the stereochemistry of the synthetized compounds and the antifungal or antimicrobial activities.
They must include the equipment specification.
Some written mistakes should be corrected.
Line 116 Add a coma after was prepared
Line 123 Add a coma after to NMR spectra
Line 123 Verify the verb form The hybrids contains,
Line 163 Verify the verb form where some signal are
For example, In lines 103, 172 & 190 CHANGE compound by compound. In line 149 CAHNGE unexpeted BY unexpected. Line 185 CANGE abcence BY absence.
Verify some terms that may be miswritten such as sustraction, concd, homodrimanic, dublet
Author Response
Comments/suggestions |
Answers: |
In general, the manuscript is relevant for the field. However, in the introduction section, the authors need to introduce some applications of the sesquiterpenoids for a better compensation. |
We agree with you, but the applications of homodrimanic sesquiterpenoids and their biological activities are described well enough in references [10-16] cited in this manuscript, and to a lesser extent in references [17-20]. |
On the results, the authors should explain in more detail the interrelation between the stereochemistry of the synthetized compounds and the antifungal or antimicrobial activities. |
It was mentioned in Results. |
They must include the equipment specification. |
The specifications were included. |
Line 116 Add a coma after was prepared |
Added |
Line 123 Add a coma after to NMR spectra |
Added |
Line 123 Verify the verb form The hybrids contains, |
The hybrids involve, |
Line 163 Verify the verb form where some signal are |
some signals are |
lines 103, 172 & 190 CHANGE compund by compound. |
Compound |
line 149 CAHNGE unexpeted BY unexpected |
Unexpected |
Line 185 CANGE abcence BY absence |
Absence |
Verify some terms that may be miswritten such as sustraction, concd, homodrimanic, dublet |
The terms were verified. |
Round 2
Reviewer 1 Report
Following corrections in English are suggested.
All compound numbers should be boldface.
Double arrow in Scheme 5 is not suitable to indicate tautomerization, because the arrow indicates resonance.
In the designation of temperature in Schemes, place blank space between a figure and °C. The circle in °C looks like 0..
In the designation of optical rotation in the experimental section, D should not be italic.
L20: chlorides –> chlorides,
L21: was –> were
L-26: results > result
L-28: established –> proposed
L-29: Caspofungin –> caspofungin
L30: Kanamycin –> kanamycin
L28: delete “a”. “Activity” is an uncountable noun.
L31: ditto
L43: ditto
L33: activity –> activities
L63: delete “as promoter”. Lawssons’ reagent is a reagent, not a promoter. It actually reacts.
L-79: first –> at first
L-80: based on –> from
L-80: remove “first”
L82: delete “of the last”
L107: The structures of intermediary compounds as well as final products were
L121: confirm –> confirmed
L-125: 135°, 45°
L-129: becames –> was
L-140: leaded –> led
L-142: triphenylphosphoxide –> triphenylphosphine oxide
L144: leads –> led
L145: gives –> gave
L-183: was –> were
L195: delete “a”
L-282: led –> lead
L-284: set –> elucidated
L-233: An effort was made –> effort was devoted, “Effort” is an uncountable word.
L-234: delete “mentioned before”
L-278: there were well visible –> down field shifts were observed
L-282: led –> lead
L-330: became –> was, at –> by
L-411: According to the first one, it interacted –> The first role is to interact with axial-----
L411: from amide –> of the amide
L-429: Caspofungin –> caspofungin
L-433: Kanamycin –> kanamycin
L-500: The –> the
L-524: “Pressure” is an uncountable noun.
L-799: (9 mL) –> (9 mL),, by ––> with
L-804: remove second “was added”.
Author Response
Hello!
Thank you very much for suggestion and corrections, for the time and effort invested.
We did all the required in the second revision changes.
Best wishes.
Sincerely,
Prof., Dr. Aculina Aricu
Author Response File: Author Response.docx