Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Carbohydrate doai
Patent
1987-10-02
1991-04-09
Griffin, Ronald W.
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Carbohydrate doai
536 182, 536115, 536119, 536 53, 435100, 514 25, A61K 3171, A61K 3170, C07H 1306
Patent
active
050065149
DESCRIPTION:
BRIEF SUMMARY
FIELD OF THE INVENTION
The present invention relates to novel .alpha.,.alpha.-trehalose trimycolates and pharmaceutical compositions which are useful as pharmaceuticals.
BACKGROUND OF THE INVENTION
It is already known that when a microbe of the genus Arthrobacter, Corynebacterium, Nocardia or Mycobacterium, capable of utilizing a sugar, such as glucose, fructose, sucrose or trehalose, to produce a lipid containing any of these sugars is cultured in a medium whose main carbon source is any of these sugars under aerobic conditions, it accumulates the glycolipid in bacterial cells or in the medium, and the mycolic acid ester of glucose, fructose, sucrose or trehalose can be obtained by recovering the accumulated glycolipid [Japanese Published and Unexamined Patent Application No. 48186/1975, Japanese Published and Unexamined Patent Application No. 3514/1978, Japanese Published and Unexamined Patent Application No. 89632/1984 and the Journal of the National Cancer Institute, 52, 95-101 (1974)].
It is also known that when a microbe capable of utilizing hydrocarbons is cultured in a medium whose carbon sources are various n-paraffins, trehalose lipid can be obtained. (Japanese Published and Examined Patent Application No. 7349/1972).
However, these glycolipids are mono- or dimycolic acid esters; when the sugar is glucose, for example, the glycolipid is the mycolic acid ester thereof at C(6-position)-OH; when the sugar is fructose, the glycolipid is the mycolic acid ester thereof at C(1-position)-OH or C(6-position)-OH, or both. In addition, even in case the sugar is the disaccharide, sucrose or trehalose, only the monomycolic acid ester thereof at C(6-position)-OH and the dimycolic acid ester thereof at C(6-position)-OH and C(6'-position)-OH are known
DISCLOSURE OF THE INVENTION
Taking note of these facts, the present inventors made investigations and found that bacteria of the genus Rhodococcus produce a glycolipid which is entirely different from conventional glycolipids. The present inventors isolated this component and made a structural analysis thereof. Also analyzed were the number of the mycolic acid molecules bonded to the sugar and the bond sites by gas chromatography/mass spectrometry (hereinafter abbreviated to GC/MS). As a result, it was confirmed that this glycolipid is a compound in which 3 molecules of mycolic acid are esterified at the specific sites in .alpha.,.alpha.-trehalose. Based on these findings, the present inventors developed the present invention.
The present invention relates to:
.circle.1 the .alpha.,.alpha.-trehalose trimycolates [hereinafter also referred to as trimycolic acid ester (I)] represented by the formula: ##STR2## (wherein R.sup.1 through R.sup.8 each represents a hydrogen atom or mycolic acid residue, and three of R.sup.1 through R.sup.8 are mycolic acid residues; these mycolic acid residues may, or may not be identical with each other), and
.circle.2 pharmaceutical compositions consisting of the trimycolic acid ester (I) and any one or more of pharmacologically allowable additives.
In the formula (I), the mycolic acid residues represented by R.sup.1 through R.sup.8 are residues having the basic structure represented by the formula: ##STR3## (wherein R' represents a straight or branched alkyl group having 8 to 26 carbon atoms with some 0 to 2 unsaturated bonds; R" represents a straight or branched aliphatic group having 20 to 60 carbon atoms (with some 1 to 9 unsaturated bonds) and the unsaturated bonds are normally double bonds. In the trimycolic acid ester (I) of the present invention, it is not necessary for the three mycolic acid residues of R.sup.1 through R.sup.8 to be all identical with each other; they may be different from each other.
However, the mycolic acid residues which can be collected from bacteria of the genus Rhodococcus are mainly those having a total of 60 to 80 carbon atoms. In addition, the most important biochemical feature of the mycolic acid residues contained in the trimycolic acid ester (I) obtained from bacteria of the genus Rhodococcus
REFERENCES:
patent: 4243663 (1981-01-01), Azuma et al.
patent: 4307229 (1981-12-01), Liav et al.
patent: 4454119 (1984-06-01), Fukushi
patent: 4612304 (1986-09-01), Fukushi
patent: 4684719 (1987-08-01), Nishikawa et al.
Azuma et al.; J. Nat. Cancer Inst., 52(1):95-101, Jan. 1974.
Lederer; Chemistry and Physics of Lipids, 16:91-106, 1976.
Rapp et al.; J. Gen. Microbiol., 115:491-503, 1979.
Liav et al.; Carbohyd. Res., 125:323-328, 1984.
Shimakata et al.; Arch. Biochem. Biophys., 238(2):497-508, May 1985.
Butler et al.; J. Clin. Microbiol., 23(1):182-185, Jan. 1986.
Tomiyasu et al.; FEBS Letters, 203(2):239-242, Jul. 1986.
Butler et al.; J. Clin. Microbiol., 25(1):2126-2131, Nov. 1987.
Gendre et al.; Bull. Soc. Chim., France, (1956), pp. 1478-1482.
Kato Yoshiko
Kurano Satoko
Shogaki Takeshi
Yano Ikuya
Yoshinaga Junji
Carson Nancy S.
Griffin Ronald W.
Sawai Pharmaceutical Co., Ltd.
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