Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1995-08-15
1997-12-02
Peselev, Elli
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 64, 536 181, C07H 100
Patent
active
056937725
DESCRIPTION:
BRIEF SUMMARY
TECHNICAL FIELD
This invention relates to desalaninebenanomicin A derivatives which are novel antifungal antibiotics, and it also relates to processes for synthesizing the same. This invention is further concerned with desalaninebenanomicin A which is an intermediate for the synthesis of the desalaninebenanomicin A derivatives, and it also relates to a process for preparing desalaninebenanomicin A. Furthermore, this invention embraces a process for the preparation of benanomicin A from desalaninebenanomicin A.
BACKGROUND ART
As such compounds similar in their structure to the desalaninebenanomicin A derivatives which are the novel antifungal antibiotics of this invention, there are benanomicin A which is produced by an actinomycetes, Actinomadura spadix MH193-16F4 strain discovered by the present inventors, Antibiotics" Vol. 41, page 807(1988), U.S. Pat. No. 5,055,453, European Patent Application Publication No. 0315147, Japanese Patent Application Publications (Kokai) Nos. HEI 1-121293, HEI 1-168694, HEI 3-187391 and HEI 2-96317!, as well as pradimicin-series antibiotics which are produced by al., "J. Antibiotics", Vol. 41, page 1701(1988), Sawada et al., "J. Antibiotics", Vol. 43, page 1367(1990)!.
These known antibiotics are all characterized by that their chemical structure has a sugar moiety at the 5-position of a 2-carboxyl group by amido-linkage. In these known antibiotics which have the above chemical structure and are known as the products of the actinomycetes, said amino acid moiety as bonded to the 2-carboxyl group is limited to glycine, alanine and serine. There is no precedent trying to make chemical synthesis of such derivatives of said antibiotics wherein the amino acid moiety has been chemically converted into another amide acid residue.
Through a detailed study by the present inventors, it has been ascertained that, among these antibiotics of benanomicin and pradimicin-series, benanomicin A which has a neutral .beta.-D-xylosyl-.beta.-D-fucosyloxy group as the sugar moeity at the 5-position and has D-alanine as the amino (Kokai) No. HEI 1-121293, U.S. Pat. No. 5,055,453 and European Patent Application Publication No. 0315147! can exhibit excellent antifungal activities and antiviral activities and also has a low toxicity and a high solubility in water, as compared with the other similar antibiotics. Thus, tests for estimating the safety of benanomicin A are now made with intention to develop it as pharmaceutical drug. Novel semi-synthetic antibiotics are therefore now expected to be produced newly by chemical conversion of benanomicin A.
In the past, a variety of antifungal antibiotics and chemically synthetic antifungal agents have heretofore been studied, but there is only a few of the antifungal agent which have a low toxicity but can exhibit a high antifungal effect. Accordingly, there has been a continued demand for providing novel antifungal agents useful in the field of therapeutic treatment of various infectious diseases caused by fungi.
DISCLOSURE OF THE INVENTION
An object of this invention is to provide new antibiotics having high antifungal activities by a process in which an antibiotic of benanomicin and pradimicin-series is modified by chemically changing the amino acid as bonded to the 2-carboxyl group of the latter antibiotic. In this invention, there are provided novel desalanine-benanomicin A derivatives in which the amino acid as bonded to the 2-carboxyl group of benanomicin A has been converted into threonine, allothreonine, butyrine or aminomalonic acid; as well as processes for the preparation of the same. When the amino acid moiety present in said novel desalaninebenanomicin A derivatives can exist as its D-isomer or L-isomer, the D-isomer is preferred for its capability to afford a higher antifungal activities. This invention also embraces a process for the synthesis of not only such novel derivatives where the amino acid as bonded to the 2-carboxyl group of benanomicin A has been converted into an amino acid of the above-described type such as threonine, but
REFERENCES:
patent: 4973673 (1990-11-01), Sanada et al.
patent: 5055453 (1991-10-01), Takeuchi et al.
patent: 5414073 (1995-05-01), Okuyama et al.
Ikeda Daishiro
Kondo Shin-ichi
Nishizuka Toshio
Takeuchi Tomio
Peselev Elli
Zaidan Hojin Biseibutsu Kagaku Kenkyu Kai
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