uchebnik_dlya_aspirantov

Table 3. Physical and Chemical Data of Compounds 4-17a

a A. indicates that the microanalysis for C, H, and N was within 0.4% of the theoretical value. B indicates that the high-resolution mass spectrometric analysis was satisfactory. C indicates that the lowresolution CIMS (NH3) was correct. …..

TASKS:

1.What are the main points covered in this section of the paper? Which techniques used in this paper do you find helpful in writing the body of your paper?

2.Read the list of phrases and choose the most appropriate ones to write the body of your paper.

List of phrases to write the body of the paper:

Methods and Techniques

1.The experiments were performed at … .

2.The experimental set up included … .

3.Two array configurations were used.

4.The measurements … were conducted using … .

5.The main experimental configuration is presented in Figure 1.

6.The simulation starts with … .

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7.The instrumentation and general arrangements were those described previously … .

8.All the experiments were carried out using a …

9.A standard … was used to … .

10.The velocity distribution in the … is obtained numerically using the finite element method.

11.The experimental … is fitted with an array of …, as shown schematically in Fig. … .

12.The equation governing the direct problem is obtained by … .

13.The direct problem is solved using the… method.

14.The following procedure is used to determine … .

15.Figure 3 summarizes the direct model and inverse approach.

16.At any given time … the inverse algorithm determines … .

17.… was verified by measuring the … at various axial locations.

18.The device was similar in concept to that described by …

19.The probe itself consisted of …

20.… was recorded by the computer for a set sampling rate and time.

21.The outside diameter of the tube is taken to be …

22.… was studied under steady state conditions.

Results

1.The results of … numerical calculations are shown in … .

2.The results obtained indicated that … .

3.A schematic diagram of the system is shown in Fig. 1.

4.Charts / tables/ figures show … .

5.From the graph it can be seen that there is good agreement between

6.experiment and theory for … .

7.The data cover a wide range of … dimensions and operating conditions.

8.As shown in Fig…, the discrepancy between the equation and the data is as much as … .

9.The present correlation is in good agreement with most data.

10.Prior to applying the inverse procedure to experimental results… .

11.Two observations can be made from these plots.

12.Fig. … shows a scatter plot of … .

13.Table … summarizes the results … .

14.Results of the … are presented in …

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15.As expected, the … errors decreased with … more rapidly.

16.The fact that the … errors are larger than the … errors suggests one of two things: …

17.Similar observations can be made about the behavior of the mean errors.

18.In general, there is no significant qualitative difference between the

… and … cases.

19.The data are plotted in logarithmic form, for ease of comparison with… paper

20.From Fig. … it is estimated that …

21.On the basis of these results it can be observed that …

* * *

To describe results use tentative verbs and modals:

It appears/seems/ is likely/ that … These results suggest …

It is possible that …;

Use past tense.

TASKS:

1.How long did it take you to write the body of the paper? What was the most difficult thing about it?

2.Read the list of phrases and choose the most appropriate ones to finish your paper.

List of phrases to write the conclusion/discussion section

1.This research has attempted to … .

2.The original assumption was that … .

3.The findings of … suggest that … is appropriate to … .

4.Analogous results hold for … .

5.One reason could be that … .

6.These results could be explained by assuming that … .

7.It is unlikely that … .

8.These findings suggest/imply/provide evidence that … .

9.Detailed understanding of … is still lacking … .

10.The method becomes even more efficient for the … case.

11.From a computational viewpoint … .

12.In this context these results are the same as those obtained from the

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… method.

13.The methods described here have more general application … .

14.It was observed that … does not have a significant effect on the

15.performance of the … equations.

16.The principal results and findings are as follows … .

17.Analyses of experimental data obtained during … demonstrate that the inverse procedure is capable of accurately predicting … over significant periods of time.

18.The results from … were compared with results from … .

19.The model will be useful in the analysis of … processes.

20.A significant advantage of this theory is that … .

21.It should be noted that the results recorded here are rather preliminary.

22.Finally, an important conclusion follows from … .

23.It is a logical consequence of the fact that … .

24.It would be interesting to … .

25.Much further research is needed in the area of … .

TASK 1: Read the following recommendation which will help you avoid certain mistakes while writing the conclusion of your paper.

Avoid:

–afterthoughts or additional ideas - now is the time to end the paper, not to begin a new thought

–the use of “thus,” “in conclusion,” or “finally” at the beginning of the last paragraph. Readers can see plainly the end of the paper.

–ending the paper without a sense of closure.

–questions that raise new issues; however, rhetorical questions that restate the issues are acceptable.

TASK 2: Read samples 3–5 and notice how to write the “Discussion of Results”, “Conclusion” and “Acknowledgements’ parts of a research paper.

Sample 3

Results and Discussion

A complex mixture of products results from the reaction of a methanolic solution of ammonia with artemisinin as determined by TLC.

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A 1H NMR spectrum of the mixture suggested the presence of a methyl ketone, but no signal characteristic of an aldehydic proton was observed. Apparently the amide nitrogen or hydroperoxide moieties form adducts with the aldehyde (e.g. 3c,d, respectively, in Scheme 1).

Prolonged reaction of 2 and ammonia produces a more complex mixture containing polar products. Avery et al.4 synthesized several artemisinin derivatives by treating crude mixtures of hydroperoxides with acid. They employed Amberlyst 15 in their early work4b but in later publications reported superior yields with a mixture of aqueous sulfuric acid/silica gel (H 2SO4 /SiO2).4c

Treatment of the crude reaction mixture from 2 and ammonia with H2SO4 / SiO2, as described by Avery et al.,4c produced a mixture of two products separable by column chromatography.5 The major product, 11azaartemisinin (4), was obtained in 45 % yield and a more polar product, 10-azadesoxyartemisinin (5), in 9 % yield. The structural assignments of 4 and 5 were based on 1H and 13C NMR and mass spectrometric data. When Amberlyst 15 was substituted for H2SCO4 / SiO2, the yield of 4 increased to 65 % and compound 5 was not observed.

The conversion of artemisinin into a lactam led us to attempt to prepare N-substituted 11-azaartemisinins using alkylamines instead of ammonia. The reaction of a methanolic solution of allylamine with 2 produced a mixture of products which on treatment with dilute H2SO4/SiO2 yielded N-allyl-11- azaartemisinin, 6, in 45 % yield along with N-allyl-10-azadesoxyartemisinin, 7, in 15 % yield.

Reaction of 2 with aromatic and heteroaromatic amines was also examined. In order to obtain N-substituted 11-azaartemisinins, it proved essential to remove any unreacted amine present in the reaction mixture prior to treatment with acid. Failure to do so resulted in formation of Nsubstituted 10-azadesoxy-artemisinins. Volatile amines could be removed in vacuo, whereas the less volatile amines required extraction of a methylene chloride solution of the crude reaction mixture with an aqueous citrate buffer (pH 4.5) Freshly distilled benzylamine and 2 with the modified workup yielded 13. Reaction of 2 with the heterocyclic amines, 2-(aminomethyl) pyridine, 2-(aminomethyl)-thiophene, and 2-(aminomethyl) furan, followed by acid treatment yielded compounds 14–16.

In exploring the use of 11-azaartemisinins as potential intermediates for the preparation of antimalarial drugs, several reactions of 4 and 6

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were investigated. Reaction of compound 4 with allyl bromide in the presence of silver oxide yielded a compound isomeric with 6. Its structure has been assigned as that of the O-allyl derivative 12 based on an analysis of its 1H and 13C NMR spectra, mass spectrometric data, and the known reactivity of amides with alkyl halides in the presence of base.6 Ozonolysis of the double bond in 6 yielded aldehyde 17.

The above N-substituted 11-azaartemisinins were screened against a chloroquine-resistant strain (FCR3) of P. falciparum using a previously published8 modification of the method of Desjardins et al.9 The in vitro test results are summarized in Table 1 and demonstrate that replacement of the lactone moiety of 2 by a lactam, as in 4, yields an antimalarial drug with equivalent biological activity. The antimalarial activities of 8, 14, and 17 were 1 order of magnitude greater than that of artemisinin. These findings are consistent with those found by Avery et al.4a for their desmethylartemisinin derivatives, i.e., the antimalarial activities of lactams were as great as or greater than that of artemisinin. The presence of the endoperoxide for antimalarial activity was essential as with other artemisinin derivatives; 3a the oxides possess no significant anti-malarial activity. Although additional data are needed for a precise comparison of the relative in vitro activities of 17 and 2, we proceeded to prepare sufficient quantities of 17 for in vivo testing. The in vivo test data are given in Table 2, which shows that 17 is at least 4 times more active than

2; i.e., it is approximately as active as в-arteether.

Neither recent clinical trials2a,b,d,e nor earlier clinical studies in China2c found artemisinin derivatives to be toxic. However, reports by Brewer et al.7 indicate that repeated administration of в-arteether, 1b, produces neurotoxic reactions in animals. In evaluating the potential of 17 as an antimalarial drug, data on its toxicity and bioavailability will be required. Additional azaartemisinin derivatives will be prepared as part of our planned structure – activity relationship (SAR) studies.

Sample 4

Conclusions

Conversion of the lactone moiety of artemisinin into a lactam does not reduce its biological activity. Two N-substituted 11-azaartemisinins were found to exhibit enhanced in vitro antimalarial activity compared to 2. In vivo test data show that the lactam 17 is ca. 4 times more active than 2

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and as potent as в-arteether. Replacement of the endoperoxide moiety in 11-azaartemisinins by an oxide results in loss of antimalarial activity. The in vitro and in vivo activities of N-substituted azaartemisinins indicate that additional derivatives should be prepared and studied.

Sample 5

Acknowledgements

1.We appreciate helpful discussions with Prof. A. and Dr. B.

2.I thank Mr. C and Mr. D for supportive comments, constructive suggestions and discussions.

3.This work was supported by the DOE under Grant No … .

4.The author is grateful for Grant No … from … .

5.The authors wish to express their sincere thanks to Dr. X. and Dr. Y. for their invaluable assistance in … , and for their penetrating criticism.

TASK: Decide what techniques the authors use to finish their paper. What do you like/dislike about it?

Unit 4. Proofreading the paper

When typing the final manuscript, pay special attention to the format and layout of your paper (margins, spacing, arrangement of the text, etc.) and then proofread it. Read the paper several times to detect and correct all possible types of errors. A computer can be very helpful with checking the spelling, grammar, and style.

Double-check in-text citations to be certain that each one is correct and that each source is listed in the “Works Cited” or “References” page at the end of the paper.

TASK: Proofread your paper and ask your fellow-students to do the same. What errors have you/ your fellow-students noticed? What techniques did you use?

Unit 5. Acknowledging Sources

Having written your paper, you should list the reference materials used to give credit to those sources, and to enable readers to consult the sources for further information. You can label this page “Works/ Sources

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Cited”, “Bibliography”, or “References” depending on the character of items included – all works related to the subject or only those quoted; printed works as well as nonprint items, e.g., speeches. Although there is no universally agreed-upon system for acknowledging sources, first, write down name of author, next, title of publication, and then publication source, date, and page. Alphabetize the entries according to the author’s last name, e.g.

References

[1 ] Alin, M. H., Ashton, M., Bjorkman, A. In vitro activity of artemisinin, its erivatives, and pyronari-dine against different strains of Plasmodium falciparum. Tmia R. Soc. Trop. Med. Hyg. 1990, 84, 635-637.

[2]WHO.Tenth Programme Report of UNDP/World Bank/WHO Special Programme for Research and Training in Tropical Diseases. WHO: Geneva, 1991; p 30.

[3]……………………………………………………………..

TASK: Look through the “References” pages in the journals on the subject of your research and write a reference page of your paper.

Unit 6. AN ABSTRACT

An abstract is a brief description of the paper. It summarizes the basic ideas developed in the paper. The abstract, as well as the title, helps readers decide to read or to skip the paper. Therefore, it should be accurate, concise, specific, objective and self-contained.

As a rule, the abstract is placed at the beginning of the paper, below the title. It is written last, when the final version of the paper is produced.

Providing an abstract in English will give your work a much higher profile outside your own country and make it much more accessible to international workers in the same field.

There are two types of abstracts: informational and descriptive.

recommendations.

3.Highlight essential points.

4.Are short – from a paragraph to a page or two, depending upon the length of the report (10 % or less of the report).

5.Allow readers to decide whether they want to read the report.

Descriptive Abstracts, which describe the publication itself (e.g. surveys, review articles, book chapters, etc.), rather than report particular findings:

1.Tell what the report contains.

2.Include purpose, methods, scope, but not results, conclusions, and recommendations.

3.Are always very short – usually less than 100 words.

4.Introduce subject to the readers, who must then read the report to learn/study results.

TASK 1: Read sample 6. What king of an abstract is it?

Sample 6

ABSTRACT

Syntheses and Antimalarial Activities

of N-Substituted 11-Azaartemisinins

Daniel S. Torok and Herman Ziffer*

National Institutes of Health, Building 5, Bl-31, Bethesda, Maryland 20892-0510

Steven R. Meshnick and Xing-Qing Pan

Department of Epidemiology, University of Michigan School of Public Health,

Ann Arbor, Michigan 48109-2029

Arba Ager

University of Miami School of Medicine, Center for Tropical Parasitic Diseases, Department of Microbiology and Immunology, 12500 S. W. 152nd Street, Miami, Florida 33177

A two-step reaction sequence between artemisinin and methanolic ammonia followed by treatment with Amberlyst 15 yielded 11azaartemisinin in 65 % yield. Substituting a variety of primary alkyland heteroaromatic amines for ammonia in the reaction sequence yields N- substituted 11azaartemisinins in similar or greater yield. When Amberlyst 15 is replaced by a mixture of sulfuric acid/silica gel, both 11azaartemisinin and the expected metabolite, 10-azadesoxyartemisinin, are

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formed in 45 % and 15 % yields, respectively. In vitro and in vivo test data for a number of novel Nsubstituted 11-azaartemisinins, against drugresistant strains of Plasmodium falciparum, show they possess antimalarial activities equal to or greater than that of artemisinin. The most active derivative, N-(2'-acetaldehydo)- 11-azaartemisinin, 17, was 26 times more active in vitro and 4 times more active in vivo than artemisinin.

TASK 2: Whichever type of abstract you write, follow the recommendations given below:

–do not repeat the information given in the title;

–do not include in the abstract any facts or ideas that are not in the text; eliminate unnecessary background information;

–decide the degree of detail you include (especially for informational abstracts);

–use direct, straightforward English; reduce wordy phrases; avoid argon;

–use the past tense when describing what was done;

–finally, revise the opening statement to emphasize the new

information contained in the paper.

What strategies to write an abstract do you find most helpful? Which оnes are you going to use?

TASK 3: Read the list of phrases and choose the most appropriate ones to write the abstract of your paper.

List of phrases to write an abstract

1.A quantitative model is presented … .

2.It is shown that … effects are … .

3.The present model shows that … .

4.An upper bound of …between … and … is established for … .

5.By examining inherent structures for … it becomes clear that … .

6.… are shown to have higher/lower indices than … to exceed conventional bounds.

7.… were observed and studied under … conditions.

TASK 4: Now write the abstract of your research paper.

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