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Showing posts with label CD spectroscopy. Show all posts
Showing posts with label CD spectroscopy. Show all posts

Saturday 31 October 2015

Computed NMR spectra predicts the structure of Nobilisitine A

Nobilisitine A was isolated by Evidente and coworkers, who proposed the structure 1.1 Banwell and co-workers then synthesized the enantiomer of 1, but its NMR did not correspond to that of reported for Nobilisitine A.; the largest differences are 4.7 ppm for the 13C NMR and 0.79 ppm for the 1H NMR.2

1
Lodewyk and Tantillo3 examined seven diastereomers of 1, all of which have a cis fusion between the saturated 5 and six-member rings (rings C and D). Low energy conformations were computed for each of these diasteromers at B3LYP/6-31+G(d,p). NMR shielding constants were then computed in solvent (using a continuum approach) at mPW1PW91/6-311+G(2d,p). A Boltzmann weighting of the shielding contants was then computed, and these shifts were then scaled as described by Jain, Bally and Rablen4 (discussed in this post). The computed NMR shifts for 1 were compared with the experimental values, and the mean deviations for the 13C and 1H svalues is 1.2 and 0.13 ppm, respectively. (The largest outlier is 3.4 ppm for 13C and 0.31 for 1H shifts.) Comparison was then made between the computed shifts of the seven diasteomers and the reported spectrum of Nobilisitine A, and the lowest mean deviations (1.4 ppm for 13C and 0.21 ppm for 1H) is for structure 2. However, the agreement is not substantially better than for a couple of the other diasteomers.

2
They next employed the DP4 analysis developed by Smith and Goodman5 for just such a situation – where you have an experimental spectrum and a number of potential diastereomeric structures. (See this post for a discussion of the DP4 method.)The DP4 analysis suggests that 2 is the correct structure with a probability of 99.8%.
Banwell has now synthesized the compound with structure 2 and its NMR matches that of the original natural product.6 Thus Nobilisitine A has the structure 2.

References

(1) Evidente, A.; Abou-Donia, A. H.; Darwish, F. A.; Amer, M. E.; Kassem, F. F.; Hammoda, H. A. m.; Motta, A., "Nobilisitine A and B, two masanane-type alkaloids from Clivia nobilis,"Phytochemistry, 1999, 51, 1151-1155, DOI: 10.1016/S0031-9422(98)00714-6.
(2) Schwartz, B. D.; Jones, M. T.; Banwell, M. G.; Cade, I. A., "Synthesis of the Enantiomer of the Structure Assigned to the Natural Product Nobilisitine A," Org. Lett., 2010, 12, 5210-5213, DOI:10.1021/ol102249q
(3) Lodewyk, M. W.; Tantillo, D. J., "Prediction of the Structure of Nobilisitine A Using Computed NMR Chemical Shifts," J. Nat. Prod., 2011, 74, 1339-1343, DOI: 10.1021/np2000446
(4) Jain, R.; Bally, T.; Rablen, P. R., "Calculating Accurate Proton Chemical Shifts of Organic Molecules with Density Functional Methods and Modest Basis Sets," J. Org. Chem., 2009, DOI:10.1021/jo900482q.
(5) Smith, S. G.; Goodman, J. M., "Assigning Stereochemistry to Single Diastereoisomers by GIAO NMR Calculation: The DP4 Probability," J. Am. Chem. Soc., 2010, 132, 12946-12959, DOI:10.1021/ja105035r
(6) Schwartz, B. D.; White, L. V.; Banwell, M. G.; Willis, A. C., "Structure of the Lycorinine Alkaloid Nobilisitine A," J. Org. Chem., 2011, ASAP, DOI: 10.1021/jo2016899




a tour

MYSORE, KARNATAKA, INDIA
Map of mysore




































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Absolute Configuration of (+)-Erythro-Mefloquine

 








The absolute configuration of (+)-erythro-mefloquine has been confirmed by X-ray crystallography, CD spectroscopy, and molecular modeling
Read more
http://www.chemistryviews.org/details/ezine/4948391/Absolute_Configuration_of_-Erythro-Mefloquine.html


  • Absolute Configuration and Antimalarial Activity of erythro-Mefloquine Enantiomers,
    Alexandra Dassonville-Klimpt, Christine Cézard, Catherine Mullié, Patrice Agnamey, Alexia Jonet, Sophie Da Nascimento, Mathieu Marchivie, Jean Guillon, Pascal Sonnet,
    ChemPlusChem 2013.
    DOI: 10.1002/cplu.201300074
  • The Absolute Configuration of (+)- and (−)-erythro-Mefloquine,
    Michael Müller, Claudia M. Orben, Nina Schützenmeister, Manuel Schmidt, Andrei Leonov, Uwe M. Reinscheid, Birger Dittrich, Christian Griesinger,
    Angew. Chem. Int. Ed. 2013.
    DOI: 10.1002/anie.201300258
  • 1-Adamantyl cation – Predicting its NMR spectra

    1-Adamantyl cation – Predicting its NMR spectra

    What is required in order to compute very accurate NMR chemical shifts? Harding, Gauss and Schleyer take on the interesting spectrum of 1-adamantyl cation to try to discern the important factors in computing its 13C and 1H chemical shifts.1

    1
    To start, the chemical shifts of 1-adamtyl cation were computed at B3LYP/def2-QZVPP and
    MP2/qz2p//MP2/cc-pVTZ. The root means square error (compared to experiment) for the carbon chemical shifts is large: 12.76 for B3LYP and 6.69 for MP2. The proton shifts are predicted much more accurately with an RMS error of 0.27 and 0.19 ppm, respectively.
    The authors speculate that the underlying cause of the poor prediction is the geometry of the molecule. The structure of 1 was optimized at HF/cc-pVTZ, MP2/cc-pVTZ and CCSD(T)/pVTZ and then the chemical shifts were computed using MP2/tzp with each optimized geometry. The RMS error of the 12C chemical shifts are HF/cc-pVTZ: 9.55, MP2/cc-pVTZ: 5.62, and CCSD(T)/pVTZ: 5.06. Similar relationship is seen in the proton chemical shifts. Thus, a better geometry does seem to matter. The CCSD(T)/pVTZ optimized structure of 1 is shown in Figure 1.

    1
    Figure 1. CCSD(T)/pVTZ optimized structure of 1.
    Unfortunately, the computed chemical shifts at CCSD(T)/qz2p//CCSD(T)/cc-pVTZ are still in error; the RMS is 4.78ppm for the carbon shifts and 0.26ppm for the proton shifts. Including a correction for the zero-point vibrational effects and adjusting to a temperature of 193 K to match the experiment does reduce the error; now the RMS for the carbon shifts is 3.85 ppm, with the maximum error of 6 ppm for C3. The RMS for the proton chemical shifts is 0.21ppm.
    The remaining error they attribute to basis set incompleteness in the NMR computation, a low level treatment of the zero-point vibrational effects (which were computed at HF/tz2p), neglect of the solvent, and use of a reference in the experiment that was not dissolved in the same media as the adamantyl cation.
    So, to answer our opening question – it appears that a very good geometry and treatment of vibrational effects is critical to accurate NMR shift computation of this intriguing molecule. Let the
    computational chemist beware!

    References

    (1) Harding, M. E.; Gauss, J.; Schleyer, P. v. R., "Why Benchmark-Quality Computations Are Needed To Reproduce 1-Adamantyl Cation NMR Chemical Shifts Accurately," J. Phys. Chem. A, 2011, 115, 2340-2344, DOI: 10.1021/jp1103356













    //////////

    Welwitindolinones structure



    A quick note here on the use of computed NMR to determine stereochemical structure. The Garg group synthesized two “oxidized welwitindolines”, compounds 1 and 2.1 The relative stereochemistry at the C3 position (the carbon with the hydroxy group) was unknown.

    1

    2
    Low energy gas-phase conformers of both epimers of 1 and 2 were optimized at B3LYP/6-31+G(d,p). (These computations were done by the Tantillo group.) See Figure 1 for the optimized lowest energy conformers. Using these geometries the NMR chemical shifts were computed at mPW1PW91/6-311+G(d,p) with implicit solvent (chloroform). The chemical shifts were Boltzmann-weighted and scaled according to the prescription (see this post) of Jain, Bally and Rablen.2 The computed chemical shifts were then compared against the experimental NMR spectra. For both 1and 2, the 13C NMR shifts could not readily distinguish the two epimers. However, the computed 1H chemical shifts for the S epimer of each compound was significantly in better agreement with the experimental values; the mean average deviation for the S epimer of 2 is 0.08 ppm but 0.36ppm for the R epimer. As a check of these results, DP4 analysis3 (see this post) of 2 indicated a 100% probability for the S epimer using only the proton chemical shifts or with the combination of proton and carbon data.

    1

    2
    Figure 1. B3LYP/6-31+G(d,p) optimized geometries of the
    lowest energy conformations of 1 and 2.

    References

    (1) Quasdorf, K. W.; Huters, A. D.; Lodewyk, M. W.; Tantillo, D. J.; Garg, N. K., "Total Synthesis of Oxidized Welwitindolinones and (-)-N-Methylwelwitindolinone C Isonitrile," J. Am. Chem. Soc. 2011,134, 1396-1399, DOI: 10.1021/ja210837b
    (2) Jain, R.; Bally, T.; Rablen, P. R., "Calculating Accurate Proton Chemical Shifts of Organic Molecules with Density Functional Methods and Modest Basis Sets," J. Org. Chem. 2009, 74, 4017-4023, DOI: 10.1021/jo900482q.
    (3) Smith, S. G.; Goodman, J. M., "Assigning Stereochemistry to Single Diastereoisomers by GIAO NMR Calculation: The DP4 Probability," J. Am. Chem. Soc. 2010, 132, 12946-12959, DOI:10.1021/ja105035r








    /////

    Sunday 21 July 2013

    Computed NMR spectra predicts the structure of Nobilisitine A


    Nobilisitine A was isolated by Evidente and coworkers, who proposed the structure 1.1 Banwell and co-workers then synthesized the enantiomer of 1, but its NMR did not correspond to that of reported for Nobilisitine A.; the largest differences are 4.7 ppm for the 13C NMR and 0.79 ppm for the 1H NMR.2

    1
    Lodewyk and Tantillo3 examined seven diastereomers of 1, all of which have a cis fusion between the saturated 5 and six-member rings (rings C and D). Low energy conformations were computed for each of these diasteromers at B3LYP/6-31+G(d,p). NMR shielding constants were then computed in solvent (using a continuum approach) at mPW1PW91/6-311+G(2d,p). A Boltzmann weighting of the shielding contants was then computed, and these shifts were then scaled as described by Jain, Bally and Rablen4 (discussed in this post). The computed NMR shifts for 1 were compared with the experimental values, and the mean deviations for the 13C and 1H svalues is 1.2 and 0.13 ppm, respectively. (The largest outlier is 3.4 ppm for 13C and 0.31 for 1H shifts.) Comparison was then made between the computed shifts of the seven diasteomers and the reported spectrum of Nobilisitine A, and the lowest mean deviations (1.4 ppm for 13C and 0.21 ppm for 1H) is for structure 2. However, the agreement is not substantially better than for a couple of the other diasteomers.

    2
    They next employed the DP4 analysis developed by Smith and Goodman5 for just such a situation – where you have an experimental spectrum and a number of potential diastereomeric structures. (See this post for a discussion of the DP4 method.)The DP4 analysis suggests that 2 is the correct structure with a probability of 99.8%.
    Banwell has now synthesized the compound with structure 2 and its NMR matches that of the original natural product.6 Thus Nobilisitine A has the structure 2.

    References

    (1) Evidente, A.; Abou-Donia, A. H.; Darwish, F. A.; Amer, M. E.; Kassem, F. F.; Hammoda, H. A. m.; Motta, A., "Nobilisitine A and B, two masanane-type alkaloids from Clivia nobilis,"Phytochemistry, 1999, 51, 1151-1155, DOI: 10.1016/S0031-9422(98)00714-6.
    (2) Schwartz, B. D.; Jones, M. T.; Banwell, M. G.; Cade, I. A., "Synthesis of the Enantiomer of the Structure Assigned to the Natural Product Nobilisitine A," Org. Lett., 2010, 12, 5210-5213, DOI:10.1021/ol102249q
    (3) Lodewyk, M. W.; Tantillo, D. J., "Prediction of the Structure of Nobilisitine A Using Computed NMR Chemical Shifts," J. Nat. Prod., 2011, 74, 1339-1343, DOI: 10.1021/np2000446
    (4) Jain, R.; Bally, T.; Rablen, P. R., "Calculating Accurate Proton Chemical Shifts of Organic Molecules with Density Functional Methods and Modest Basis Sets," J. Org. Chem., 2009, DOI:10.1021/jo900482q.
    (5) Smith, S. G.; Goodman, J. M., "Assigning Stereochemistry to Single Diastereoisomers by GIAO NMR Calculation: The DP4 Probability," J. Am. Chem. Soc., 2010, 132, 12946-12959, DOI:10.1021/ja105035r
    (6) Schwartz, B. D.; White, L. V.; Banwell, M. G.; Willis, A. C., "Structure of the Lycorinine Alkaloid Nobilisitine A," J. Org. Chem., 2011, ASAP, DOI: 10.1021/jo2016899

    Welwitindolinones structure

    A quick note here on the use of computed NMR to determine stereochemical structure. The Garg group synthesized two “oxidized welwitindolines”, compounds 1 and 2.1 The relative stereochemistry at the C3 position (the carbon with the hydroxy group) was unknown.

    1

    2
    Low energy gas-phase conformers of both epimers of 1 and 2 were optimized at B3LYP/6-31+G(d,p). (These computations were done by the Tantillo group.) See Figure 1 for the optimized lowest energy conformers. Using these geometries the NMR chemical shifts were computed at mPW1PW91/6-311+G(d,p) with implicit solvent (chloroform). The chemical shifts were Boltzmann-weighted and scaled according to the prescription (see this post) of Jain, Bally and Rablen.2 The computed chemical shifts were then compared against the experimental NMR spectra. For both 1and 2, the 13C NMR shifts could not readily distinguish the two epimers. However, the computed 1H chemical shifts for the S epimer of each compound was significantly in better agreement with the experimental values; the mean average deviation for the S epimer of 2 is 0.08 ppm but 0.36ppm for the R epimer. As a check of these results, DP4 analysis3 (see this post) of 2 indicated a 100% probability for the S epimer using only the proton chemical shifts or with the combination of proton and carbon data.

    1

    2
    Figure 1. B3LYP/6-31+G(d,p) optimized geometries of the
    lowest energy conformations of 1 and 2.

    References

    (1) Quasdorf, K. W.; Huters, A. D.; Lodewyk, M. W.; Tantillo, D. J.; Garg, N. K., "Total Synthesis of Oxidized Welwitindolinones and (-)-N-Methylwelwitindolinone C Isonitrile," J. Am. Chem. Soc. 2011,134, 1396-1399, DOI: 10.1021/ja210837b
    (2) Jain, R.; Bally, T.; Rablen, P. R., "Calculating Accurate Proton Chemical Shifts of Organic Molecules with Density Functional Methods and Modest Basis Sets," J. Org. Chem. 2009, 74, 4017-4023, DOI: 10.1021/jo900482q.
    (3) Smith, S. G.; Goodman, J. M., "Assigning Stereochemistry to Single Diastereoisomers by GIAO NMR Calculation: The DP4 Probability," J. Am. Chem. Soc. 2010, 132, 12946-12959, DOI:10.1021/ja105035r

    Sunday 7 July 2013

    SPECTROSCOPY DATA of ASPIRIN








     Dear blog reader , this post is for brushing up our fundamentals of spectroscopy using simple molecules like aspirin
    text may be less but graphs are educative. one can browse through this to brush up

    Acetylsalicylic Acid


    Product Name: Acetylsalicylic acid CAS:50-78-2










    1H NMR



     
        Assign.     Shift(ppm)
    
          A            11.
          B             8.125
          C             7.624
          D             7.356
          E             7.142
          F             2.352
      ABOVE IS PROTON NMR OF ASPIRIN AND ITS INTERPRETATION
    
    
    
    
    
    
    
    
    abelled.
    structure of aspirin
    The peaks I have are:
    • 2.30ppm (I this is a singlet and would be F)
    • 7.07ppm (I think this is E)
    • 7.29ppm (I think this is D)
    • 7.53ppm (I think this is C)
    • 8.05ppm (I think this is B)
    • 11.44ppm (this is a singlet and would be A)
    For B,C,D,E I need to say what kind of splitting pattern there would be and how many coupling constants are present and there approximate value. I think I know the assignments of them but I don't know the splitting pattern or coupling constants.
    Would E and B be doublet of doublets because they couple with D and C so they would have ortho and meta coupling?
    Would D and C be coupling with each other and B and E so would they be doublet of doublets of doublets, with two ortho and one meta coupling?
    
    
    
    
    
    
    
    
    
    
    
    
     
     




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     BELOW IS IR OF ASPIRIN KBR DISC









    IR in nujol mull

    ....................................................................................................................................................................



    MASS SPECTRUM







    above is mass spectrum of aspirin

    o-acetoxybenzoic acid
    C9H8O4              (Mass of molecular ion:    180)

     Source Temperature: 170 °C
       Sample Temperature: 100 °C
       DIRECT, 75 eV
    
    

    13 C NMR

     


    above is 13 C NMR OF ASPIRIN

    50.18 MHz
    C9 H8 O4 0.039 g : 0.5 ml CDCl3


     ppm   Int.  Assign.
    
          170.20   450      1
          169.76   510      2
          151.28   560      3
          134.90   924      4
          132.51  1000      5
          126.17   986      6
          124.01   974      7
          122.26   397      8
           20.99   674      9


    =================================================

    Animasi Kimia

    below is Raman spectra of aspirin





    NMR INTERPRETATIONS

    H-NMR spectral analysis
    Acetylsalicylic acid NMR spectra analysis, Chemical CAS NO. 50-78-2 NMR spectral analysis, Acetylsalicylic acid H-NMR spectrum
    CAS NO. 50-78-2, Acetylsalicylic acid H-NMR spectral analysis
    C-NMR spectral analysis
    Acetylsalicylic acid NMR spectra analysis, Chemical CAS NO. 50-78-2 NMR spectral analysis, Acetylsalicylic acid C-NMR spectrum
    CAS NO. 50-78-2, Acetylsalicylic acid C-NMR spectral analysis




    H, H-COSY spectrum

    In H, H-COSY spectrum are on both axes, the 1 H chemical shifts plotted; In principle, both the axes 1 to see H-NMR spectra. Thus, there is a symmetric to the diagonal diagram.
    1 H-NMR spectrum of acetylsalicylic acid

    Fig.2
    H, H-COSY spectrum of acetylsalicylic acid
    In the spectrum, only the range from 7.0 to 8.2 ppm is applied, because only here HH scalar couplings can be expected.

    Fig.3
    There are two types of signals:
    • Diagonal signals: join the coordinates δ a Î´ a (in core A), δ b Î´ b (in core B) ... on, but play no role in the evaluation of the couplings between different cores, since it is only the signal of a nucleus is. The diagonal with all its signals corresponding to the 1D H-NMR spectrum.
    EXAMPLE
    Acetylsalicylic acid
    7.13 ppm / 7.13 ppm = δ 2 Î´ 2 (H atom 2)
    7.34 ppm / 7.34 ppm = δ 4 Î´ 4 (H atom 4)
    7.61 ppm / 7.61 ppm = δ 3 Î´ 3 (H atom 3)
    8.11 ppm / 8.11 ppm = δ 5 Î´ 5 (H atom 5)
    • Cross signals: These signals are based on the scalar spin-spin coupling and are suitable for the evaluation of spectra of enormous importance.
    EXAMPLE
    Acetylsalicylic acid
    7.13 ppm / 7.61 ppm (δ 2 Î´ 3 ), and 7.61 ppm / 7.13 ppm (δ 3 Î´ 2 ) - vicinal coupling between the H-atoms 2 and 3
    7.34 ppm / 7.61 ppm (δ 4 Î´ 3 ) and 7.61 ppm / 7.34 ppm (δ 3 Î´ 4 ) - vicinal coupling between the H-atoms 4 and 3
    7.34 ppm / 8.11 ppm (δ 4 Î´ 5 ) and 8.11 ppm / 7.34 ppm (δ 5 Î´ 4 ) - vicinal coupling between the H-atoms 4 and 5
    In general it can be seen in the COSY spectrum each scalar coupling between two nuclei at four signals (two cross and two diagonal peaks) resulting connected a square; in the following example, the vicinal coupling between the H atoms is highlighted 3 and 4.

    Fig.4
    With good resolution of the COSY spectrum, the coupling constants can be determined from the fine structure of the cross and diagonal signals, but this is rarely done because of the 1-D H-NMR spectra is easily possible.
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    Khajuraho Group of Monuments is located in India
    Khajuraho Group of Monuments
    Location of Khajuraho Group of Monuments in India.

    Location in Madhya PradeshLocation in Madhya Pradesh

    1. Khajuraho Group of Monuments - Wikipedia, the free ...

      en.wikipedia.org/wiki/Khajuraho_Group_of_Monuments

      The Khajuraho Group of Monuments are a group of Hindu and Jain temples in Madhya Pradesh, India. About 620 kilometres (385 mi) southeast of New Delhi, ...























    Hotel Chandela - A Taj Leisure Hotel

























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