Organic compounds -- part of the class 532-570 series – Organic compounds – Heterocyclic carbon compounds containing a hetero ring...
Patent
1996-03-08
1997-01-28
Ramsuer, Robert W.
Organic compounds -- part of the class 532-570 series
Organic compounds
Heterocyclic carbon compounds containing a hetero ring...
C07D30928
Patent
active
055979335
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP94/01940 filed Jun. 15, 1994.
The present invention relates to a process for the preparation of derivatives of N-acetyl neuraminic acid. More particularly the invention relates to a process for the preparation of 5-acetamido-4-amino-2,3,4,5-tetradeoxy-D-glycero-D-galacto-non-2-enopyrano sonic acid (the 4-amino analogue of DANA; also known as 5-(acetylamino)-4-amino-2,6-anhydro-3,4,5-trideoxy-D-glycero-D-galacto-non -2-enonic acid).
Schreiner et. al. Ann. Chem 1991, 129-134 describe the preparation of the 4-amino analogue of DANA from the peracetylated methyl ester of sialic acid (peracetyl NANA methyl ester) by the route shown in Scheme 1.
PCT/AU91/00161 (publication no. WO91/16320) describes the preparation of a number of derivatives of 5-acetamido 2,3,5-trideoxy-D-glycero-D-galacto-non-2-enopyranosonic acid (2,3-dideoxy-2,3-didehydro-N- acetyl-neuraminic acid; DANA) including the 4-amino analogue of DANA from the peracetylated methyl ester of DANA by a method similar to that of Schreiner et. al. with the exception that the peracetylated compound (3a) was reduced prior to deacetylation. The method is shown in Scheme 2.
Our copending application no. PCT/EP92/02904,publication no. WO 93/12105, published Jun. 24, 1993, describes a process for the preparation of 4-amino DANA from the corresponding peracetyl-4-azido analogue by catalytic hydrogenation using gaseous hydrogen.
We have now found that the yield and purity of 4-amino DANA can be improved by modification of the conversion of peracetyl 4-azido DANA to 4-amino DANA described in PCT/EP92/02904.
The invention thus provides a method for the preparation of the compound of formula (I) ##STR3## which comprises catalytic hydrogenolysis of a compound of formula (II) ##STR4## (wherein R is H or a C.sub.1-4 alkyl group and R.sup.1 is H or a hydroxyl protecting group for example an acyl group such as acetyl) in aqueous formic acid followed, where necessary, by hydrolysis.
By aqueous formic acid is meant a solution of formic acid in water or a mixture of water and any compatible organic solvent miscible with water. Preferably the solvent is water. Formic acid is conveniently present in an amount of 1-4 molar equivalents, for example about 2 molar equivalents of the compound of formula (II).
The formic acid acts as the source of hydrogen for the hydrogenolysis. It will be appreciated by those skilled in the art that the hydrogenolysis of the compound of formula (I) results in the liberation of nitrogen gas; it is thus advantageous to employ formic acid rather than hydrogen gas as the source of hydrogen.
The catalytic reduction may be effected with any suitable catalyst. In one preferred embodiment the catalyst is a palladium catalyst but in particular a poisoned palladium catalyst. A preferred poisoned palladium catalyst is a Pd catalyst poisoned with lead for example a Lindlar Catalyst. A particularly preferred catalyst comprises 5% palladium on a suitable support such as barium sulphate or, preferably, calcium carbonate, and 3 to 7% lead by weight of catalyst, such as 4 to 6% lead, more preferably 5% lead.
In an alterative preferred embodiment the catalyst is an unpoisoned catalyst, in particular, a palladium catalyst, for example palladium on charcoal.
The reduction is conveniently carried out at 0.degree.-50.degree. C., preferably at 20.degree.-30.degree. C.
In a preferred aspect of the invention the compound of formula (II) is deprotected, that is to say that R and R.sup.1 are both hydrogen. The compound of formula (II) wherein R and R.sup.1 are both hydrogen may be obtained by hydrolysis of the corresponding compound of formula (II) wherein R is a C.sub.1-4 alkyl group and R.sup.1 is a hydroxyl protecting group such as acetyl. The hydrolysis may be effected with any suitable inorganic or organic base. Preferably an organic base such as triethylamine or, particularly, 1,8-diazabicylo [5.4.0]undec-7-ene (DBU) is employed. Water or a mixture of water and any compatible organic solvent miscible with water is conveniently employ
REFERENCES:
E. Schreiner et al., "Synthesis of Some 2,3-Didehydro-2-deoxysialic Acids Structurally Varied at C-4 and their Behavior towards Sialidase from Vibrio cholerae", Liebigs Annalen der Chemie, vol. 1991, No. 2, Feb. 1991, pp. 129-134.
Searle Andrew D.
Williamson Christopher
Biota Scientific Management Pty. Ltd.
Ramsuer Robert W.
Stockton Laura L.
LandOfFree
Process for the preparation of N-acetyl neuraminic acid derivati does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Process for the preparation of N-acetyl neuraminic acid derivati, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Process for the preparation of N-acetyl neuraminic acid derivati will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-942325