Drug – bio-affecting and body treating compositions – Designated organic active ingredient containing – Having -c- – wherein x is chalcogen – bonded directly to...
Reexamination Certificate
2001-05-17
2003-09-23
Solola, Taofiq (Department: 1626)
Drug, bio-affecting and body treating compositions
Designated organic active ingredient containing
Having -c-, wherein x is chalcogen, bonded directly to...
C514S460000, C549S292000, C549S293000, C424S401000, C585S455000
Reexamination Certificate
active
06624190
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The present invention relates to new substituted 2-acylamino-2-deoxy-glucono-1,5-lactone type compounds, to compositions containing said compounds that are surfactants and/or biologically active compounds, to methods for producing said compounds and to intermediates in their production.
2. Prior Art
Examples of glycosylated surfactants comprising a lactone function have been cited in the literature. Pocalyko et al., (1996) (5) and Kwoh et al. (1995) (3) describe the enzymatic synthesis of 6—O-dodecyl gluconolactone, while Kida et al. (1994) (1) use the lactone function to synthesise surfactants that are degradable in an acidic medium.
However, such lactones do not contain an N-acyl moiety or an N-acetylglucosamine moiety; this moiety is important in the recognition of certain enzymes.
Examples of the synthesis of N-acetyl glucosaminidase inhibitors have been cited in the literature by Pokorny et al., (1974) (6); Wolk et al. (1992) (7); Knapp et al. (1996) (2); and Panday et al. (1998) (4). These inhibitors exhibit major disadvantages; in particular, their low dissociation constant (between 0.13 and 0.45 &mgr;M) makes these potent inhibitors useless as regards affinity separation, as recovering the enzyme requires operating conditions that could cause them to denature. None of the molecules concerned has surfactant properties, in particular 2-acetamido-2-deoxy-glucono-1,5-lactone (Pokorny et al., 1974). As a result, their purely hydrophilic nature does not enable them to interact with biological membranes with a view to possible cellular penetration or disruption, or with amphiphilic compounds organised into micelles or liposomes with a view to vectorising or to liquid/liquid separation.
We have now developed a new class of substituted 2-acylamino-2-deoxy-glucono-1,5-lactone type compounds that may have the advantage of having surfactant or biodegradability properties and may be biologically active.
BRIEF SUMMARY OF THE INVENTION
The present invention provides compounds with formula (I):
where A represents R
1
or —C(O)R
1
, where R
1
represents a linear or branched, saturated or unsaturated alkyl group containing 1 to 30 carbon atoms, which may be partially or completely substituted by —Hal where Hal signifies —Cl, —Br, —I or —F, and which may be interrupted by one or more moieties selected from —O, —S—, —C(O)—, —NR
3
C(O)—, —Ph(R
4
)
n —
, and —CH
2
—CH
2
—O)
n′—
, where R
3
represents —H or —CH
2
)
n″
—CH
3
where n″ is 0 to 17; R
4
represents —H, —CH
3
, —C
2
H
5
, —C
3
H
7
and n is 0 to 4 and n′ is 1, 2 or 3, or R
1
represents a cyclane radical with a diterpene or triterpene root; and R
2
represents a linear or branched C
1
to C
11
alkyl group.
The compounds of the invention have the advantages of glycosylated glucosamine-based surfactants such as biodegradability.
Further, some of these compounds may have antimicrobial and antifungal properties. Finally, these compounds may be useful in enzymatic inhibition or enzyme recognition methods.
The invention al so concerns methods for preparing compounds with the above formula I. These methods comprise at least the following steps:
a) acylating glucosamine hydrochloride using an acid chloride with formula R
2
C(O)Cl;
b) protecting the C1 hydroxyl group by a P
1
group, and the C3 and C4 hydroxyl group by groups P
2
and the C6 hydroxyl group;
c) deprotecting the protected C6 hydroxyl group;
d) 6—O-acylation with a compound with formula R
1
C(O)Cl or 6—-alkylation with a compound with formula R
1
Hal to obtain the compound with formula:
e) deprotecting the protected C1 hydroxyl group to obtain the compound with formula:
f) oxidising the compound obtained at e) to obtain the compound with formula:
g) deprotecting the protected C3 and C4 hydroxyl groups of the compound obtained in f) to obtain the compound with formula I;
where A, R
2
and Hal have the same meanings as those given above, and P
1
and P
2
are protective groups.
In a further aspect, the invention concerns, as intermediate compounds, compounds with the following formulae:
where A, R
2
, P
1
and P
2
have the meanings given above.
Further, the present invention concerns compositions comprising at least one or more compounds of the invention, one or more compounds obtained by the method of the invention or intermediate products in said method.
Finally, the invention concerns compounds with formula I as surfacts or compounds for use in an enzymatic inhibition method or an enzyme recognition method.
The present invention will be better understood from detailed description and examples below and from the accompanying figures.
REFERENCES:
patent: 5505938 (1996-04-01), Pocalyko et al.
patent: 5728661 (1998-03-01), Petit et al.
patent: 0 808 842 (1997-11-01), None
Wolk et al., “28. synthesis and enzyme-inhibition studies of phenylsemicarbazones dervied fromD-Glucono-1,5-lactone and 2-Acetamido-2-deoxy-D-glucono-1,5-lactone,”Helvetica Acta,vol. 75, pp. 323-334 (1992).
Knapp et al., “NAG-thiazoline, An N-Acetyl-&thgr;-hexosaminidase inhibitor that implicates acetamido participation,”J. Am. Chem. Soc.,vol. 118, pp. 6804-6805 (1996).
Kida et al., “New cleavable surfactants derived from Glucono-1,5-Lactone,”JAOCS,vol. 71, No. 7, pp. 705-710 (Jul. 1994).
Kwoh et al., “Regioselective synthesis and characterization of 6-O-alkanoylgluconolactones,”Carbohydrate Research,vol. 274, pp. 111-121 (1995).
Pokorny et al., “The inhibitory activity of 2-acetamido-2-deoxy-D-gluconolactones and their isopropylidene derivatives on 2-acetamido-2-deoxy-&thgr;-D-glucosidase,”Carbohydrate Research,vol. 37, pp. 321-329 (1974).
Panday et al., “Synthesis and evaluation of indolizine-type inhibitors of N-Acetyl-&thgr;-D-glucosaminidases,”Helvetica Chimica Acta,vol. 81, pp. 475-490 (1998).
Kitagawa et al., “Chemical Transformation of Uronic Acids Leading to Aminocyclitols. II. Synthesis of Hexaacetyl-streptamine from N-Acetyl-D-Glucosamine”,Chemical and Pharmaceutical Bulletin,vol. 26, No. 12, pp. 3825-3831, 1978.
Yoshikawa et al., “Chemical Transformation of Uronic Acids leading to Aminocycliols. IV. Synthesis of Hexaacetyl-streptamine from N-Acetyl-D-Glucosamine by means of Electrolytic Degradation”,Chemical and Pharmaceutical Bulletin,vol. 29, No. 9, pp. 2582-2586, 1981.
2000, International Search Report for PCT/FR99/02861.
Khoury Chadi
Le Goffic Francois
Minier Michel
Merchant & Gould P.C.
Solola Taofiq
Universite Pierre et Marie Curie (Paris VI)
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