Asiatic acid derivatives having modified A-ring

Details Asiatic acid derivatives having modified A-ring Asiatic acid derivatives having modified A-ring

1999-05-25

2000-06-06

Badio, Barbara

Drug, bio-affecting and body treating compositions

Designated organic active ingredient containing

Cyclopentanohydrophenanthrene ring system doai

514893, 552510, A61K 3156, C07J 5300

Patent

active

060718986

DESCRIPTION:

BRIEF SUMMARY
PRIOR FOREIGN APPLICATIONS

This application is a 371 of PCT/KR97/00240, filed Nov. 27, 1997 and claims priority from KR patent application numbers 1996/58174, filed Nov. 27, 1996 and 1997/6656, filed Feb. 28, 1997.


TECHNICAL FIELD

The present invention relates to asiatic acid derivatives having modified A-ring, which are represented by formula 1: ##STR2## wherein, R.sub.1 represents a lower alkyl group having 1-4 carbon atoms, an alkoxy group having 1-4 carbon atoms, hydroxymethyl group, a halomethyl group or an aldehyde group which may be protected by ethanedithiol; R.sub.2 represents a lower alkyl group having 1-4 carbon atoms, t-butyldimethylsilyloxymethyl group, a halomethyl group, --CH.sub.2 OCO(CH.sub.2).sub.n CO.sub.2 H (n=0.about.3), --CH.sub.2 OCOCHCHC.sub.6 H.sub.5, or hydroxy methyl group which may be protected by acetyl or benzoyl group; R.sub.3 represents hydrogen or methyl group; and the double bond of 2-position may be reduced to form a single bond; same as an active component.


BACKGROUND ARTS

These asiatic acid derivatives have been prepared by modifying A-ring of asiatic acid or methyl asiatate. The modification has been already performed to decide the structural formula of asiatic acid, and reported. [B. Singh and R. P. Rastogi, Phytochemistry, 8, 917-921, 1969]
Asiatic acid and asiaticoside (trisaccharide of asiatic acid) and madecassic acid, which are compounds extracted from Centella asiatica, were isolated firstly by Bontems in 1941 [J. E. Bontems, Bull. Sci. Pharmacol., 49, 186-96 (1941)], and their structure was defined by Polonsky and his colleagues.[J. Polonsky, Compt. Rend., 232, 1878-80 (1951): J. Polonsky, Bull. Soc. Chim., 173-80 (1953)].
The extract including asiatic acid and asiaticoside from Centella asiatica have been used for treatment of hurted skin or chronic ulcer since old times, and also for treatment of skin deformation owing to tuberculosis or leprosy. [P. Boiteau, A. Buzas, E. Lederer and J. Polonsky, Bull. Soc. Chim., 31, 46-51 (1949)]
Recently, it was reported that various triterpenes which have similar structure to asiatic acid extracted from plants, in particular, ursolic acid, show effect on cytotoxicity. [K. Yasukawa, Oncology, 48, 72-76 (1991); Dominic, Y. Alex, Med. Sci. Res., 21(5), 213-215 (1993); Ryu, Shi young, Arch. Pharamacal Res., 17(5), 375-7(1994)] It was reported that betulinic acid, which can be easily synthesized from its precursor isolated from the bark of white birch, shows cytotoxicity against melanoma cells without substantial side effect. [Nat. Med., 1, 1046(1995)]


DISCLOSURE OF THE INVENTION

The present inventors have performed intensive studies to develop novel pharmaceutical compositions having various medical use, and as a result, they synthesized various derivatives having modified A-ring, starting from asiatic acid obtained from Centella asiatica. They also found that the derivatives have cytotoxicity and liver-protecting function and completed the invention.
The object of the present invention is to provide asiatic acid derivatives.
The present invention relates to asiatic acid derivatives represented by general formula 1: ##STR3## wherein, R.sub.1 represents a lower alkyl group having 1-4 carbon atoms, an alkoxy group having 1-4 carbon atoms, hydroxymethyl group, a halomethyl group or an aldehyde group which may be protected by ethanedithiol; R.sub.2 represents a lower alkyl group having 1-4 carbon atoms, t-butyldimethylsilyloxymethyl group, a halomethyl group, --CH.sub.2 OCO(CH.sub.2).sub.n CO.sub.2 H (n=0.about.3), --CH.sub.2 OCOCHCHC.sub.6 H.sub.5, or hydroxy methyl group which may be protected by acetyl or benzoyl group; R.sub.3 represents hydrogen or methyl group; and the double bond of 2-position may be reduced to form a single bond; same as an active component.
The process for preparing the asiatic acid derivatives having modified A-ring according to the present invention is illustrated here-in-below:
1) Asiatic acid (2) is treated with diazomethane to obtain methyl asiatate (3, R.sub.3 =methyl) quantatively, which

REFERENCES:
Singh et al., A reinvestigation of the triterpenes of centella asiatica>' Phytochemistry, ol. 8, pp. 917-921, 1969.
Osman, A.M. et al., "Chemical studies on pentacyclic triterpenes," Chem Abstr, 79:9249d (1973).

Affiliated with

Also associated with

Rating

Asiatic acid derivatives having modified A-ring does not yet have a rating. At this time, there are no reviews or comments for this patent.

If you have personal experience with Asiatic acid derivatives having modified A-ring, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Asiatic acid derivatives having modified A-ring will most certainly appreciate the feedback.

Rate now

Comments { 0 }

Profile ID: LFUS-PAI-O-2213697