Chiral derivatives of Garcinia acid bearing lactone ring...

Details Chiral derivatives of Garcinia acid bearing lactone ring... Chiral derivatives of Garcinia acid bearing lactone ring...

2001-09-05

2002-12-03

Owens, Amelia (Department: 1625)

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

Organic compounds

Heterocyclic carbon compounds containing a hetero ring...

C548S453000

Reexamination Certificate

active

06489492

ABSTRACT:

FIELD OF INVENTION
This invention relates to novel chiral derivatives bearing lactone moiety of Garcinia acid and a process for preparing the same.
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.
Garcinia acid for formula Ia is widely used as an important ingredient in many pharmaceutical formulations
1-10
.
The non-availability of Ia 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.09/365,301,1999 an economic, commercially viable, cost effective process for the large-scale isolation of Ia has been described
11
.
Also during the past two decades there has been a great deal of interest to find cheap and potential chiral molecules from chiral pool to accomplish synthetic pathways with a high degree of asymmetric induction
12-25
.
Added to this, substituted &ggr;-butyrolactones are known to be potent antagonists or agonists depending upon the substitution pattern of the &ggr;-aminobutyric acid receptor, the major inhibitory neurotransmitter in the mammalian central nervous system
26
.
The known methods for obtaining diversity functionalised chiral &ggr;-lactones are either by the cyclisation of acyclic starting materials such as the sterioselective iodolactonisation of unsaturated 3-hydroxy acids
27
or from sugars such as D-ribofiranose or D-glucosamine or carbohydrates such as D-ribose, D-glucose etc
28
. These chemical: modifications involving carbohydrates require tedious protocols.
SUMMARY OF THE INVENTION
The object of this invention therefore is to prepare novel chiral derivatives of Garcinia acid and the process of preparing the same.
To achieve the objective this invention provides novel chiral derivatives of
Garcinia acid bearing lactone ring moiety of formula I-
wherein:
R
1
=R
3
=alkali salt of carboxyl acid, or acid chloride or part of N-substituted cyclic imides.
R
2
=hydroxyl or protected hydroxyl group.
In the above formula I
R
2
is —OH or protected hydroxyl group. To form various chiral derivatives of Garcinia acid bearing lactone ring moiety.
Chiral Derivatives of Garcinia Acid Bearing Lactone Ring Moiety
Summary of the chiral derivatives of Garcinia acid bearing lactone ring moiety is given below in scheme I:
The present invention further provides a process of preparation of Formula Ib comprising:
treating an aqueous solution of Ia with an aqueous solution of alkali till the pH of the solution is neutral,
evaporating the solution to dryness,
washing the residue with water miscible organic solvent,
drying the product Ib in vaccum.
The said alkali is sodium bicarbonate.
The invention further includes a process for the preparation of novel chiral derivative of formula Ic, comprising:
adding an organic halide to a suspension of Ib in organic solvent,
stirring the mixture for 1-4 hours,
filtering the said mixture,
evaporating the said solution to get Ic as a hygroscopic solid.
The said organic solvent is ether.
The said organic halide is thionyl chloride.
The invention further includes a process for the preparation of novel chiral derivative of formula Id comprising:
adding DMSO, an organic acid and an anhydride to If,
allowing the mixture to stand for 3-4days,
adding the reaction mixture to cold saturated aqueous solution of alkali,
stirring the mixture for 1-4 hours,
extracting the resultant solution with an organic solvent,
washing the extract with aqueous alkali,
drying the organic layer,
evaporating to get crude Id,
purifying the crude Id by chromatography to get pure Id as an yellow oil.
The said organic acid is acetic acid.
The said anhydride is acetic anhydride.
The said alkali is sodium bicarbonate.
The invention further includes a process of preparation of novel chiral derivative of formula Ig comprising:
refluxing the suspension of Ia in an organic halide for 3 hours,
concentrating the said mixture under vacuum,
dissolving the solid obtained in an organic solvent,
adding an appropriate amine to the dissolved solution,
stirring the mixture at room temperature for 4-18 hours,
concentrating the solution under vacuum,
adding the organic halide to the semi-solid obtained,
refluxing for 18 hours,
extracting with suitable organic solvent,
subjecting the said extract to chromatography furnishing Ig as white crystals.
The said organic halide is acetyl chloride.
The said appropriate amine is 4-methoxy benzyl amine.
The said organic solvent is chloroform.
The process will now be described with reference to the following examples.


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patent: WO 9636585 (1996-11-01), None
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Chemical Abstracts, vol. 96, 1982, p. 236, Section 96:3042ln and 96:30422p.
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Ortuno, Merce and Font, “Reactions of Some D-Ribonolactone Derivatives . . . ”, Tetrahedron, vol. 43, No. 19, pp. 4497-4506.
Cardellach et al., “Studies on Structurally Simple . . . ”, Tetrahedron, vol. 38, No. 15, pp. 2377-2394.
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Drioli et al., “Synthesis of (+)—and (−)- Phaseolinic . . . ”, J. Org. Chem. , 1998, 63, pp. 2385-2388.

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