Organocatalyzed enenatioselective

1. ORGANOCATALYSED
ENANTIOSELECTIVE CYCLIZATION
REACTIONS FOR THE SYNTHESIS Of
DIHYDROPYRANO [3, 2-C] CHROMENE
DERIVTIVES
Presented by
Aijaz ah bhat
11200628

2. O O
O
Z
H
R
NH2
O
O
OH
O
Warfarin
O O
OH
4-HYDROXY COUMARIN
O O
COUMARIN

3. Medicinal properties
 The molecular mechanism of multidrug
resistance (MDR) in cancer cells may
involve the over-expression membrane
drug effux pumps, p53 mutation and up
regulation of bcl-2,DNA repair or cellular
detoxification enzymes.
 Warfarin revealed a particular hopefully
results in treatment of Small Cell
Carcinoma Lung (SCCL) a tumor of cells,
Neurodegenerative diseases, including
Alzheimer’s disease, Antiplatelet etc.

4. INTRODUCTION
Coumarin is a sweet smelling (fragrant)
organic compound in the benzopyrone family
of compounds.
It is a colourless white crystalline substance
in its actual form.
 It is a naturally occurring compound present
in the plants.
 The term coumarin has its actually French
orign for the tonka bean (Dipteryx odorata
Wild Fabaceae).

5. Coumarou one of the sources from which
the substance was first isolated as a
natural product in 1820 by A . Vogel of
Munich.
 Also in 1820, Nicholas Jean Baptiste
Gaston Guibourt ( in 1790-1867) of France
independently isolated coumarin .
 In a succeeding esay, He presented to
the pharmacy section of Academine royale
de Medicine , Guibourt named the new
substance called “ Coumarine “ .

6.  Coumarin was first synthesized in 1868.
It is used in in the pharmaceutical
industry as a basic reagent in the
synthesis of a number of synthetic
anticoagulant pharmaceuticals similar to
Dicoumarol.
 Regarding the clinical medical value , it
act as an Edema modifer . Coumarin
should be carefully handling because it is
highly toxic with a LSD 50.

7. CHCL3
H2O,NaOH,65o
C
OH
OH
H
CH3COOH
CH3COONa
OH
COOH
O O
A

8. Occurrence of Coumarins
• There are mainly four subtypes of coumarn
these are as;
• 1 Simple coumarins
• 2 Furano coumarins
• 3 Pyrano coumarins
• 4 Pyrone substituted coumarins

9. HO O
O
7-hydroxy-3,4-dihydrochromen-2-one
1 Simple Coumarins
O O
O
psoralen
2 Furano Coumarins

10. O
O
3 Pyrano Coumarins
O
O
OH
O
4 Pyrone-Substituted Coumarin

11. Plants and plant products have a long history
of being successfully used in the treatment of
cancer disease by chemotherapeutic agents and
complementary treatements.
The pyranocoumarin compound was isolated
from Radix Peucedani, a well known herb for the
treatment of respiratory diseases and pulmonary
hypertension.
Resistance of cancer cells to chemotherapeutic
agents which remain one of the major obstacle to
achieving the effective treatment of cancer.

13. LITRATURE REVIEW
• Derivaties of pyrano [3,2-c] chromene are a
class of important hetrocycles with a different
types of properties such as anti-cancer, anti-
coagulant, dirutic etc.
• They have also power of cognitive for the
treatment of neurodegenerative diseases,
Alzheimers disease etc

15. S.No Catalyst (amount) Solvent Temperature oC
(Time, min)
% Yield
1
Piperidine or Pyridine Base Ethanol 70 (70) 45
2
DAHP (10 mol%) Ethanol-Water 25 (220) 85
3
H6P2W18O62 18H2O Ethanol-Water 30 (140) 82
4
[DBU][AC] (3.03 mol%) Solvent free 25 (5) 93
5
N,N,N’,N’-tetrabromo benzene-1,3-
disulfonamide
(TBBDA)
Ethanol-Water Reflux (180) 82
6
DBU Water Reflux (600) 40
Different methods for the synthesis of Dihydropyrano [3, 2-c] chromenes;

16. Enantioselective Organocatalyzed Three
Component Reaction in the synthesis of
Pyranocoumarins
Multicomponent reactions have gained
significant importance as a tool for the synthesis of
a wide variety of useful compounds, including
pharmaceuticals.
 In this context, the multiple component
approach is especially appealing in view of the fact
that products are formed in a single step, and the
diversity can be readily achieved simply by varying
the reacting components

17.  Enantioselective organocatalysis have emerged
as a powerful synthetic idea thatl is
complementary to metal-catalysed
transformations and has a accelerated the
development of new methods to make diverse
chiral molecules.
 water An efficient synthesis of
dihydropyrano[3,2-c]chromene can be prepared
by adding 4-
hydrocoumarin,ethylcyanoacetate,aldehydes such
as( p-methoxy benzaldehyde , 3-Nitro
benzaldehyde, ,in ethanol and water under the
reflux condition

18.  The formation of product is very regioselective.
This is an effective catalyst for the one port
syntyhesis of dihydropyrano[3,2-c]chromene.
 It is being environmently benign, processing
high yields with increased variation of the
substituent in the poroduct.

20. O O
O
NH2
COOEt
H
OMe
O O
OH CHO
COOEt
CN
+ +
8 9 a
Scheme-4
OMe
EtOH,
p-Cl-Benzoic acid
30o
C, 2.5h
Cat 10 mol%
11
Cat
N
H
N
H
N
N
N
(S)-5-(pyrrolidin-2-yl)-1H-tetrazole (received asgift)

21. Experimental Work
 Firstly we take 0.5 gm of 4 hydroxy coumarin
in 25 ml ethanol and 10 ml water and
ethylcyano acetate.
 Secondly we have used S-prolene as it is one
of the highly efficient organo catalyst resulting
into the formation of highly regioselective
product which is having a good quantum-
yield and there is no formation of side
product.

22.  We have also analyzed the enantioselective
excess due to a screened pyrrolidinyl tetrazole
organocatalyst obtained on demand from NCL
laboratory, Pune.
 The reaction was transferred into the column by
which the compounds were seperated and
collected into the flasks.
 The reactions were monitored by TLC.
 now keep the products for vaporization and
collect the crystals of the products.
 Check the melting point and also weighing.

23. Spectroscopic Data
 Products were characterized by their spectra
(UV,IR,HNMR) and physical data.
 (S)-ethyl 2-amino-4-(4-methoxyphenyl)-5-oxo-
4,5-dihydropyrano[3,2-c]chromene-3-carboxylate
(11) (sample B)
 Pale yellow flakes, Yield 65% isolated, Mol. Wt.
393, m.p. 210-214 oC, UV spectra; From the
analysis of UV data of 4-Hydroxy Coumarnin the
λ max value ranges from 276nm to 303 nm.,so it
is observed that that the two types of transition
are takes place that is n-π and π-π* respectively.

24. From the UV analysis, the λ value shifts from
276-303 nm to 362-372 nm respectively. This
shows that a drastic shift in the λ max value
(Bathochromic Shift), IR (KBr) νmax (cm-
1):3414 (N-H asym str)., 3315 (N-H sym str),
2839 (C-H), 1718 (α,β-unsat lactone C=O
str),1687 (α,β-unsat ester C=O str), 1587 (N-H
str), 1313 (C-O str.), (1185 C-O str.). 1HNMR
(CDCl3, 500 MHz): δH = 1.39 (3H, t, J = 7.0 Hz,
CH3), 3.84 (3H, s, OCH3), 4.37 (2H, m, CH2),
5.31 (1H, s, H-4), 6.65 (2H, d, J=7.8 Hz, H3´,
H5´), 6.98 (2H, d, J=8.8 Hz, H2´, H6´), 7.05 (2H,
m, H8, 9), 7.23 (2H, s, NH2), 7.27 (1H, d, J=7.5
Hz, H11)

25. Instrumental Analysis
IR compound 11

26. UV OF COMPOUND 11

27. NMR OF COMPOUND 11

28. Compound11 [B] Spectral expansion of
the aromatic region:

29. Uv of compound 13.

32. CONCLUSION
 Pyrano coumarin and its derivaties plays an
important role in the field of
therapeutic,laboratory,medicinal field etc.
 In the present study of pyrano coumarin derivaties,
the synthesis of these derivaties required single step
multi- component reaction and the catalyst used have
furnished a high enantioselective excess of the β-aryl
enantiomers that are produced in quantitative yield.
 Experimental and isolation method makes it an
attractive for the preparation of these compounds.

33. THANK YOU