Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1997-05-16
1999-02-23
Knode, Marian C.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536122, 53612313, 536124, 536 552, C07H 100, C07H 510, C07H 504
Patent
active
058745483
DESCRIPTION:
BRIEF SUMMARY
This application is a 371 of PCT/EP95/03034 filed Jul. 27, 1995 published as WO96/03413 Feb. 8, 1996.
This invention relates to regioselective sulfation; more particularly, various sulfated organic molecules, some of which are novel, have been synthesised by a sulfation method via regioselective activation of the organic molecules to certain diorganostannylene acetals, followed by treatment with electrophilic sulfating agents.
Specifically, the present invention provides a direct method for the regioselective sulfation of an organic molecule having optionally derivatized hydroxyl groups at least on two adjacent carbon atoms characterised in that it comprises the treatment of a di -(optionally substituted alkyl and/or aryl) stannylene acetal derivative thereof with an electrophilic sulfating agent.
Conventional electrophilic sulfating agents may be used for the present purposes, for example sulfur trioxide/amino-base, such as pyridine or triethylamine, but sulfur trioxide/trimethylamine is preferred. The sulfation is conveniently effected at room temperature, e.g. 20.degree.-25.degree. C., in a suitable organic solvent, such as dioxane or THF. Of course, higher temperatures may be used if desired, depending upon the choice of solvent.
The present method involves the treatment of a stannylene acetal derivative of the starting material. Such derivatives are di- (optionally substituted alkyl and/or aryl substituted. In the case of an alkyl substituent, it is preferred that it contain up to six carbon atoms, while phenyl is an example of a suitable aryl substituent. Either may itself be substituted by one or more non-interfering substituents, e.g. alkoxyl. The substitution of the stannylene acetal derivatives may be dialkyl or diaryl or it may be alkyl - aryl. In a presently-preferred embodiment, a dibutylstannylene acetal derivative is used.
Generally, the present method may be carried out by conventional means, but an immobilised system may also be envisaged.
The starting material for the present method is an organic molecule having optionally derivatized hydroxyl groups at least on two adjacent carbon atoms. For example, ether-derivatization of one of the two hydroxyl groups may influence selectivity, more particularly in that the sulfate group would tend to be directed to the other position. More specifically, a 3'-sulfate would be expected to result from a galactoside or lactoside, while a 2'-sulfate may be obtained from a partially-protected maltoside.
In the absence of interfering substituents, the present methodology may be applied to a wide variety of such organic molecules. The presence of two hydroxyl groups in proximity, one of which is to be sulfated, is central to the present method. Saccharide chemistry is an instance where such selectivity may be important, particularly in view of the number of potentially-reactive hydroxyl groups. For example, the present method is well-suited to both poly- and oligo-saccharides, preferably containing no more than twenty, more preferably no more than six, repeating units. The advantages thereof are particularly apparent in relation to mono- and di- saccharides. The present method may be applied to glycoconjugates, such as glycolipids and glycopeptides, or to glycosaminoglycans. It should be noted that this methodology may also be used with analogues of the materials illustrated above, e.g. unnatural sugars, such as amino-sugars. As will be appreciated, there is no need to distinguish between natural and synthetic molecules or polymers.
In the exemplification of the present method, a number of novel compounds are identified below, specifically those numbered 14, 15, 16, 23, 25, 30, 32 and 34, and the present invention also relates thereto. As will be explained, compound 23 is of particular interest. Of course, such organic molecules may be conjugated to larger molecules and the present invention further relates thereto. This would also apply to other sulfate products of the present method.
One embodiment of the present invention concerns the regioselective sulfa
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Maccarana, M. et
Flitsch Sabine
Guilbert Benedicte
Genzyme Corporation
Knode Marian C.
Salcedo F. Brad
White Everett
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