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Sunday 29 September 2013

PICTORIAL NMR





ETHANOL
The most simple NMR output, or spectrum, for a very simple molecule is shown in this picture on the left. It shows a 1D spectrum for ethanol.
In very simple terms it shows three different peaks representing the three different ‘proton environments’ present in the molecule. These all have different ‘frequencies’.
All protons have broadly similar ‘frequencies’, but there are subtle differences between them, and we may exploit this. These are due to local electronic environment.
Generally speaking, the more electronegative the neighbouring atoms, the greater the extent of de-shielding, and hence the ‘greater’ the frequency. In the above instance, the proton of the hydroxyl group is clearly nearest the most electronegative neighbour. This explains why it appears way to the left of the other protons. Conversely the protons of the methyl group experience the least de-shielding due to a lack electron-withdrawing neighbours (it’s safely tucked away from the oxygen atom, hidden by a methylene group), and it appears furthest to the right hand side.

File:Lipscomb-NMR-hexaborene-B6H10.png

NMR Interpretation of hexaborane

12.8 MHz. range (right)

A simple example of the chemical shift is the "a" and "b" doublets (pairs of peaks).
 "A" and "b" are two groups of boron atoms in different electronic environments, 
which place the "a" doublet to the right of the "b" doublet in the spectrum.
The relative peak heights of the "a" and "b" doublets suggest a 1:5 ratio of borons 
in one environment to borons in another environment.
This suggests, combined with the molecular weight of the molecule:
  • 5 boron atoms in one environment ("b") and
  • 1 boron atom in another environment ("a"),
which in turn suggests a pyramidal structure, which does appear in the atomic diagram.

40 MHz. range (left)

"a" suggests a hydrogen at the apex, which is in the atomic diagram sticking straight up.
"b" suggests hydrogens bonded to one boron each, which are in the 
atomic diagram sticking straight out from the edges.
"c" suggests other bridge hydrogens, which is to say hydrogens in the 
middle of a boron-hydrogen-boron bonding arrangement like a hydrogen bridge between two boron shores, 
which are in a ring around the atomic diagram.
(Williams1959)

History

X-ray diffraction was needed to be sure of the structure.(Hirshfeld1958)
More complex molecules are more challenging, although in some
 cases common subgroups of atoms produce characteristic spectral patterns, which can be recognized.

References

(Williams1959) Wiliams, R.E., Gibbins, S.G., and Shapiro, I., J. Chem. Phys, 30, 333 (1959).
(Hirshfeld1958) Hirshfeld, F. L., Eriks, K., Dickerson, R. E., Lippert, E. L., and Lipscomb, W. N.,
 "Molecular and Crystal Structure of B6H10,” J. Chem. Phys. 28, 56 (1958).
The two papers above, reviewed in: Eaton GR, Lipscomb, WN. 1969. 
NMR Studies of Boron Hydrides and Related Compounds. W. A. Benjamin, Inc.
COMPLICATED NMR

Wednesday 25 September 2013

SIMPONI® Receives European Commission Approval for Treatment of Moderately to Severely Active Ulcerative Colitis » All About Drugs

SIMPONI® Receives European Commission Approval for Treatment of Moderately to Severely Active Ulcerative Colitis » All About Drugs:

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VALSARTAN SPECTRAL DATA

 
VALSARTAN

mp 114–118 °C; 

1H NMR (400 MHz, DMSO-d6): δ 12.6 (brs, 1H), 7.72 (m, 4H), 7.24 (m, 1H), 7.15 (m, 2H), 6.94 (m, 1H), 4.58 (m, 1H), 4.40 (m, 1H), 3.33 (m, 1H), 2.25 (m, 1H), 1.52 (m, 6H), 0.9 (m, 3H), 0.84 (m, 3H), 0.74 (m, 3H); 



13C NMR (100 MHz, DMSO-d6): δ 174.0, 172.4, 171.8, 141.7, 138.2, 131.54, 131.1, 131.0, 129.3,128.8, 128.2, 127.4, 126.7, 70.3, 63.4, 49.9, 32.9, 28.05, 27.3, 22.2, 20.6, 14.2; 


ESIMS: m/z calcd [M]+: 435; found: 436 [M+H]+; HRMS (ESI): m/z calcd [M]+: 435.5187; found: 435.5125 [M]+




US 7439261 B2

1H-NMR (CDCl3) (0.80-1.15 (m, 9H); 1.20-1.50 (m, 2H); 1.60-1.80 (m, 2H); 2.60 (t, 2H); 2.65-2.80 (m, 2H), 3.70 (d, 1H), 4.10 (d, 0.3 H), 4.30 (d, 0.7 H), 4.90 (d, 0.7H), 5.2 (d, 0.3H); 7.00 (d, 0.3H); 7.10-7.20 (m, 4H), 7.40-7.60 (m, 3H), 7.85 (d, 0.7 H).



SHORT DESCRIPTION




Valsartan, N-(1-oxopentyl)-N-[[2′-(1H-tetrazol-5-yl)[1,1′-biphenyl]-4-yl]methyl]-L-valine, is a known anti-hypertensive agent having the following formula (I):
Figure US07439261-20081021-C00001
Valsartan and its preparation are disclosed in U.S. Pat. No. 5,399,578, in particular in Example 16. One of the synthetic routes according to U.S. Pat. No. 5,399,578 can be schematically represented as follows:
Figure US07439261-20081021-C00002
Figure US07439261-20081021-C00003
The synthetic pathway comprises various steps, among which:

    • coupling of compound (3) with 2-chlorobenzonitrile to obtain compound (4),
    • radicalic bromination of compound (4) to give compound (5),
    • transformation of the brominated derivative (5) into the respective aldehyde derivative (6),
    • reductive alkylation of compound (6) to obtain intermediate (8),
    • acylation of compound (8) to obtain intermediate (9),
    • conversion of the cyano group to the tetrazole group to afford intermediate (10),
    • deprotection of the carboxylic group by hydrogenolysis to obtain valsartan.
  • It is marketed as the free acid under the name DIOVAN. DIOVAN is prescribed as oral tablets in dosages of 40 mg, 80 mg, 160 mg and 320 mg ofvalsartan.
  • [0004]
    Valsartan and/or its intermediates are disclosed in various references, including: U.S. Pat. Nos. 5,399,578 ,5,965,592 5,260,325 6,271,375 WO 02/006253 WO 01/082858 WO 99/67231 WO 97/30036 , Peter Bühlmayer, et. al., Bioorgan. & Med. Chem. Let., 4(1) 29-34 (1994), Th. Moenius, et. al., J. Labelled Cpd. Radiopharm., 43(13) 1245 - 1252 (2000), and Qingzhong Jia, et. al., Zhongguo Yiyao Gongye Zazhi, 32(9) 385-387 (2001), all of which are incorporated herein by reference.
  • [0005]
    Valsartan is an orally active specific angiotensin II antagonist acting on the AT1 receptor subtype. Valsartan is prescribed for the treatment of hypertension. U.S. Pat. No. 6,395,728 is directed to use of valsartan for treatment of diabetes related hypertension. U.S. Pat. Nos. 6,465,502 and 6,485,745 are directed to treatment of lung cancer with valsartan. U.S. Pat. No. 6,294,197 is directed to solid oral dosage forms of valsartan
GOOD ARTICLES

http://users.uoa.gr/~tmavrom/2009/valsartan2009.pdf

http://www.acgpubs.org/JCM/2009/Volume%203/Issue%201/JCM-0908-14.pdf

https://www.beilstein-journals.org/bjoc/single/printArticle.htm?publicId=1860-5397-6-27 REPORTS
 mp 114–118 °C; 1H NMR (400 MHz, DMSO-d6): δ 12.6 (brs, 1H), 7.72 (m, 4H), 7.24 (m, 1H), 7.15 (m, 2H), 6.94 (m, 1H), 4.58 (m, 1H), 4.40 (m, 1H), 3.33 (m, 1H), 2.25 (m, 1H), 1.52 (m, 6H), 0.9 (m, 3H), 0.84 (m, 3H), 0.74 (m, 3H); 13C NMR (100 MHz, DMSO-d6): δ 174.0, 172.4, 171.8, 141.7, 138.2, 131.54, 131.1, 131.0, 129.3,128.8, 128.2, 127.4, 126.7, 70.3, 63.4, 49.9, 32.9, 28.05, 27.3, 22.2, 20.6, 14.2; ESIMS: m/z calcd [M]+: 435; found: 436 [M+H]+; HRMS (ESI): m/z calcd [M]+: 435.5187; found: 435.5125 [M]+




Valsartan 

Structural formula

UV - Spectrum


Conditions : Concentration - 1 mg / 100 ml
The solvent designation schedule
methanol 
water 
0.1М HCl 
0.1M NaOH 
maximum absorption249 nm250 nm248 nm251 nm
309302289311
e13400131001260013500

IR - spectrum

Wavelength (μm)
Wave number (cm -1 )

NMR spectrum


references


  • UV and IR Spectra. H.-W. Dibbern, R.M. Muller, E. Wirbitzki, 2002 ECV
  • NIST/EPA/NIH Mass Spectral Library 2008
  • Handbook of Organic Compounds. NIR, IR, Raman, and UV-Vis Spectra Featuring Polymers and Surfactants, Jr., Jerry Workman. Academic Press, 2000.
  • Handbook of ultraviolet and visible absorption spectra of organic compounds, K. Hirayama. Plenum Press Data Division, 1967.


Image result for VALSARTAN SYNTHESIS





CLIP

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Scheme 2: (a) Et3N, CH2Cl2, 0 °C, 95%; (b) NaH, THF, 70%; (c) n-BuLi, 25 °C, THF, anhyd ZnCl2, −20 °C, Q-phos, Pd(OAc)2, 75 °C, 2 h, 80%; (d) 3 N NaOH, MeOH, reflux, 90%.

http://www.beilstein-journals.org/bjoc/single/articleFullText.htm?publicId=1860-5397-6-27

valsartan 8; mp 114–118 °C; 1H NMR (400 MHz, DMSO-d6): δ 12.6 (brs, 1H), 7.72 (m, 4H), 7.24 (m, 1H), 7.15 (m, 2H), 6.94 (m, 1H), 4.58 (m, 1H), 4.40 (m, 1H), 3.33 (m, 1H), 2.25 (m, 1H), 1.52 (m, 6H), 0.9 (m, 3H), 0.84 (m, 3H), 0.74 (m, 3H); 13C NMR (100 MHz, DMSO-d6): δ 174.0, 172.4, 171.8, 141.7, 138.2, 131.54, 131.1, 131.0, 129.3,128.8, 128.2, 127.4, 126.7, 70.3, 63.4, 49.9, 32.9, 28.05, 27.3, 22.2, 20.6, 14.2; ESIMS: m/z calcd [M]+: 435; found: 436 [M+H]+; HRMS (ESI): m/z calcd [M]+: 435.5187; found: 435.5125 [M]+












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Monday 16 September 2013

Solid state NMR technique takes on Taxol

Taxol structure

Taxol's active conformation has proved a puzzle


US scientists have developed a new technique for investigating the biologically active forms of the anticancer drug Taxol.
David Grant at the University of Utah, Salt Lake City, and co-workers have used novel solid state NMR techniques to establish the structure of a unique conformation of paclitaxel - more commonly known as Taxol.

NMR IN DRUG DISCOVERY

  1. [PDF]

    NMR in Drug Discovery

    www.bioc.aecom.yu.edu/labs/.../nmr/.../Lecture_DrugDiscovery_2010.p...
    Apr 23, 2010 - 1. COURSE#1022: Biochemical Applications of NMR Spectroscopy http://www.bioc.aecom.yu.edu/labs/girvlab/nmr/course/. NMR in Drug ...


    CLICK BELOW

http://www.bioc.aecom.yu.edu/labs/girvlab/nmr/course/COURSE_2012/Lecture_DrugDiscovery_2010.pdf

NMR determination of enantiomeric purity



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Wednesday 11 September 2013

Unravelling stereochemistry via mass spectrometry

AAAS/Science
The new technique can determine the stereochemical configuration of a molecule by the way it breaks apart © Science/AAAS
News item thumbnail




Technique reveals a molecule’s chirality without separating the enantiomers or growing pure crystals

READ ALL AT
http://www.rsc.org/chemistryworld/2013/09/molecules-stereochemistry-chirality-mass-spectrometry

Saturday 7 September 2013

An alkyl shift « Naturalproductman’s Blog

alkaloids

An alkyl shift « Naturalproductman’s Blog:

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Making HSQC look nicer « Naturalproductman’s Blog

HSQC

Making HSQC look nicer « Naturalproductman’s Blog:

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 SHIRDI, MAHARASHTRA, INDIA

Shirdi - Wikipedia, the free encyclopedia

en.wikipedia.org/wiki/Shirdi
pronunciation (help·info) (Marathi: शिर्डी) is a town and falls under the jurisdiction of municipal council popularly known as Shirdi Nagar Panchayat, located ...


 Map of shirdi maharashtra.




 
 

 

 


 
 

 


 

 Shraddha Inn,Shirdi

 
 SHIRDI PRASADALAYA BOJAN

 


 Solar Kitchen Feeds Many at Shirdi, India Shrine

 

 


 Rajdhani Restaurant: Rajdhani at Shirdi

 

 The well equipped kitchen provides food two times a day, daily. Around 27, 000 of people are distributed food at cheap rate. The food comprises of dal, 

 
 





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