Acyclic chiral compound from garcinia acid and process for...

Details Acyclic chiral compound from garcinia acid and process for... Acyclic chiral compound from garcinia acid and process for...

2001-09-05

2004-03-16

Solola, Taofiq (Department: 1626)

Organic compounds -- part of the class 532-570 series

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C549S453000, C560S182000

Reexamination Certificate

active

06706899

ABSTRACT:

BACKGROUND OF THE INVENTION
Garcinia acid [(−)-Hydroxycitric acid lactone or (2S,3S)-Tetrahydro-3-hydroxy-5-oxo-2,3-furandicarboxylic acid] is isolated from the fruits of
Garcinia cambogia, Garcinia indica
and
Garcinia atroviridis
. This molecule is widely used as an important ingredient in many pharmaceutical formulations.
The non-availability of Garcinia acid in the market, in the pure form, has resulted in the limited use of these compounds in the area of organic synthesis and pharmaceutical front. This is due to the lack of any commercially viable large-scale manufacturing process. In U.S. patent application Ser. No. 09/365,300 economic, commercially viable, cost effective process for the large-scale isolation of Garcinia acid has been described.
The object of the present invention is to prepare hitherto unknown acyclic chiral molecules from Garcinia acid.
To achieve the said objective this invention provides novel chiral derivatives of Garcinia acid of formula I
wherein:
R
2
=R
5
=lower aryl/alkyl ester or substituted aryl/alkyl alcohol
R
3
=substituted aryl/alkyl ester or substituted aryl alcohol
R
1
=R
4
=hydroxyl or
In the above formula I
R
2
and R
5
is selected from —COOCH
3
,—COOC
2
H
5
, —COOCH(CH
3
)
2
, —C(Ph)
2
OH, —C(4-MePh)
2
OH, —C(1-Naphth)
2
OH
R
1
and R
4
is OH or
R
3
is selected from —CH
2
COOCH
3
, —CH
2
COOC
2
H
5
, —CH
2
COOCH(CH
3
)
2
, —CH
2
C(Ph)
2
OH, —CH
2
C(4-MePh)
2
OH, —CH
2
C(1-Naphth)
2
OH
to form various chiral derivatives, namely, chiral triesters, chiral ketals and chiral alcohols.
Chiral triester derivatives:
R
2
=R
5
=—COOCH
3
, R
1
=R
4
=—OH and R
3
=—CH
2
COOCH
3
R
2
=R
5
=—COOC
2
H
5
; R
1
=R
4
=—OH; R
3
=—CH
2
COOC
2
H
5
R
2
=R
5
=—COOCH(CH
3
)
2
; R
1
=R
4
=—OH; R
3
=—CH
2
COOCH(CH
3
)
2
Chiral ketal derivatives:
Chiral alcohol derivatives (diols):
Summary of the chiral derivatives of Garcinia acid is given below in scheme I:
The present invention further provides a process for preparing the chiral triester derivatives of formulae comprising:
refluxing garcinia acid with appropriate alcohol in presence of an inorganic catalyst for 6-12 hours,
adjusting the pH of the reaction-mixture using aqueous alkali solution,
concentrating the said reaction-mixture by evaporation, extracting the said concentrate with an organic solvent,
The said appropriate alcohols are selected from methanol, ethanol and isopropanol.
The said catalyst is conc.HCl.
The said organic solvent is chloroform.
The present invention further includes a process for preparing the chiral alcohol derivatives of formulae If to Ih comprising:
adding solution of chiral acetal/ketal in an organic solvent to a solution of appropriate grignard reagent(ArMgX) in an organic solvent,
refluxing the mixture for 10-20 hours,
adding the inorganic salt solution to the chilled reaction mixture,
collecting the organic phase and extracting the aqueous layer further with an organic acid,
drying the organic extract using an inorganic salt,
evaporating the said extract,
subjecting the residue to chromatography.
The organic solvent is tetra hydro furan (THF).
The said appropriate grignard reagent is phenyl Mg bromide, methylphenyl Mg bromide, naphthyl Mg bromide.
The said inorganic salt is ammonium chloride and organic solvent used for extraction is ether.
The salt used for drying the extract is sodium sulphate.
The chromatography employed for purification is column chromatography.
The gel used for chromatography is silica gel.
The eluant used for chromatography is hexane-chloroform mixture.
Chiral ketals were prepared using standard procedures.
The invention will now be described with reference to the following examples:
Chiral triester derivatives:


REFERENCES:
patent: 3764692 (1973-10-01), Lowenstein
patent: 6127553 (2000-10-01), Ibnusaud et al.
patent: 6147228 (2000-11-01), Ibnusaud et al.
patent: 6489492 (2002-12-01), Saud et al.
patent: 6489493 (2002-12-01), Saud et al.
Ibnusaud, I. et al. “Chiral&ggr;-butyrolactones related to optically active 2-hydroxycitric acids.” Tetrahedron vol. 58 (2002) pp. 4887-4892.
Jena, B.S. et al. “Chemistry and Biochemistry of (-)-Hydroxycitric Acid from Garcinia.” Journal of Agricultural and Food Chemistry vol. 50 (2002) pp. 10-22.
Narasaka, K. et al. “Use of 1,3-Oxazolidin-2-one Derivatives of 3-Borylpropenoic Acids as &bgr;-Hydroxy Acrylic Acid Equivalents in the Asymmetric Diels-Alder Reaction Catalyzed by a Chiral Titanium Reagent.” Tetrahedron vol. 48, No. 27 (1992) pp. 5743-5754.
Seebach, D. et al. “TADDOLs, Their Derivatives and TADDOL Analogues: Versatile Chiral Auxiliaries.” Agnew Chem. Int. Ed. vol. 40 (2001) pp. 92-138.

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