Process for preparing novel biologically active synthetic...

Details Process for preparing novel biologically active synthetic... Process for preparing novel biologically active synthetic...

2000-03-24

2001-06-26

Barts, Samuel (Department: 1621)

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

Organic compounds

Amino nitrogen containing

C564S387000

Reexamination Certificate

active

06252114

ABSTRACT:

FIELD
The invention provides a process for preparing novel biologically active synthetic molecule 4-(p-methoxyphenyl)-2-amino-butane from a naturally occurring compound 4-(p-hydroxyphenyl)-butan-2-ol. The molecule of the invention is a colorless crystalline solid, having molecular formula, C
11
H
17
ON, and structural formula (1) as represented hereunder:
C
11
H
17
ON=4-(p-methoxy phenyl)-2-amino butane
The spectral characteristics of the molecule are as follows:
The EI mass spectrum of the compound showed its M
t
at M/Z 179, thus confirming its molecular formula as C
11
H17ON, and other diagnostic fragment peaks at M/Z 162, 147, 121 and 91 IR&ngr;
max
(KBr) 3360, 2940, 1610, 1515, 14501, 1030 and 850 cm
−1
The product is a new molecule which has been prepared from a readily available starting material 4-(p-hydroxyphenyl)-butan-2-ol having structural formula (2) isolated from the plant
Taxus wallichiana.
C
10
H
14
O
2
=(4-(p-hydroxy phenyl)-butan-2-ol
BACKGROUND AND PRIOR ART
The plant
Taxus wallichiana
which also known as Himalayan yew is now considered to be one of the most needed plants for commercial exploitation as it contains the anticancer drug Taxol. Taxol, a highly oxygenated diterpenoid molecule and potent anticancer drug was first isolated from the stem bark of
Taxus brevifolia.
Thereafter, it has also been isolated from other Taxus plants including the Himalayan yew
Taxus wallichiana.
The applicants have been working on different parts of
Taxus wallichiana
collected from different pairs of India for the isolation of taxol, its important analogues and precursor 10-deacetyl baccatin III (DAB); During the course of investigation, the applicants have isolated a major compound from the leaves of
Taxus wallichiana.
The major compound was identified as 4-(p-hydroxyphenyl)-butan-2-ol having structural formula (2). This compound can be obtained with a yield of 0.2% from the leaves of
Taxus wallichiana.
Accordingly, the applicants have developed a simple and cost effective process for isolation of this compound from the leaves of
T. wallichiana.
The process of isolation of the compound comprises the steps of defatting air dried pulverised Taxus leaves with aliphatic hydrocarbon solvents, extracting the defatted leaves with chlorinated solvents and polar solvents successively, concentrating the chlorinated solvent soluble fraction to a residue and treating the residue with aqueous solution of alkali and isolating the compound from the alkali soluble fraction by acidifying it and extracting it with ethyl acetate, to obtain 4-(p-hydroxy phenyl)-butan-2-ol.having structural formula (2).
The compound (2) was not found to be active in bioassay studies for evaluation of growth inhibition and antifeedant activity. The compound of formula (2) was obtained with high yield (0.2%), converted into other structural analogues through a series of chemical reactions. In the course of this investigation, the applicants were able to prepare a new molecule represented by formula (1) from 4-(p-hydroxy phenyl)-butan-2-ol, represented by formula (2). The compound having structural formula (1) shows significant activity as a growth inhibitor and antifeedant.
The compound having formula (1) was evaluated as feeding deterrant and growth inhibitor against
4
th
in star larvae of Spilarctia Obliqua. This insect attacks more than twenty cash crops including urd, mong, arhar, mint and coleus etc.
Compound having formula (1) is non hazardous in nature and thus is ecologically safe and environmentally sound for its use as an agrochemical.
OBJECTS
The main object of this invention is to provide a new molecule, 4-(p-methoxyphenyl)-2-amino butane represented by formula (1) and represented by the molecular formula C
11
H
17
ON.
Another object of the present invention is to provide a process for the preparation of this biologically active compound represented by structural formula (1) with higher yields, from a readily available starting material isolated from the plant
Taxus wallichiana.
Yet, another object of the present invention is to obtain this important molecule through a process which avoids the use of chromatographic separation and makes the process cost effective.
DETAILED DESCRIPTION
Accordingly, the present invention provides a process for the preparation of a novel molecule 4-(p-methoxyphenyl)-2-amino butane, represented by formula (1) and having growth inhibitory and antifeedant activity. The process for the isolation of 4-(p-methoxyphenyl)-2-amino butane comprises the steps of:
a) isolating the phenolic compound represented by structural formula (2) from the leaves of
Taxus wallichiana
by known methods,
b) treating the compound having formula (2) in aqueous mineral acid at 25-100° C. for 2-10 hours to obtain a phenolic halide derivative represented by structural formula (3),
c) converting the phenolic halide derivative into its methyl ether by treating it with a methylating agent to obtain a methyl ether halide represented by structural formula (4),
d) reacting the methyl ether formed with azide into an azido derivative having structural formula (5), and
e) hydrogenating the azido compound of step (d) by catalytic hydrogenation in the presence of a catalyst in lower aliphatic alcohol to obtain 4-(p-methoxyphenyl)-2-amino butane represented by structural formula (1).
The aqueous mineral acid used in step (b) is selected from the group consisting of hydrochloric acid, hydrobromic acid and hydroiodic acid. The methylating agent used in step (c) is selected from methyl iodide or dimethyl sulphate.
The azide, used in step (d) is sodium azide or trimethyl silyl azide.
The catalyst used in the hydrogenation process is selected from palladium charcoal and platinum oxide. The lower aliphatic alcohol used as medium to dissolve the azide derivative in the hydrogenation process may be methyl alcohol, ethyl alcohol.
As mentioned earlier, the compound 4-(p-methoxy phenyl)-2-amino butane exhibits antifeedant and growth inhibiting activity against certain insects, especially the larvae of Spilarctia Obliqua.
Hence, the compound has potential use as an insecticide, and would have wide spread applications in insecticidal compositions. Without wishing to be bound by any theory, the Applicants state that an insecticidal composition comprising an effective amount of the compound 4-(p-methoxyphenyl)-2-amino butane and an adjuvant in an amount sufficient to enhance the activity of the composition may be prepared. In practice, it is found that the novel compound 4-(p-methoxyphenyl)-2-amino butane per se may also be used to control insects in fields, though it is recommended that the compound be mixed with augmenting adjuvants such as distilled water, acetone or such other solvents before use. The insecticidal compositions may be sprayed or applied in the soil for control of pests. Further, the said insecticidal composition may be effectively used for the control of insects/their larvae such as Spilarctia Obliqua. In practice, the compound is found to be very useful in controlling phytopathogenic insects and mites.
The invention is described in detail in the examples given below which are provided to illustrate the invention and therefore should not be construed to limit the scope of this invention.
The products of the reactions as described in the steps hereinbelow is represented hereunder:
C
10
H
13
OX(4-(p-hydroxyphenyl)-2-halobutane(3)
C
11
H
15
OX(4-(p-methoxyphenyl)-2-halo-butane) (4)
C
11
H
15
ON
3
=(4-(p-methoxyphenyl)-2-azido butane). (5)
C
11
H
17
ON=(4-(p-methoxyphenyl)-2-amino butane (1)


REFERENCES:
patent: 4695589 (1987-09-01), Philion
patent: 4950606 (1990-08-01), Stirling et al.
patent: 5073648 (1991-12-01), Hagishita
patent: 5169780 (1992-12-01), Stirling et al.
patent: 5300437 (1994-04-01), Stirling et al.

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