Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives
Patent
1995-03-14
1998-06-16
Fonda, Kathleen K.
Organic compounds -- part of the class 532-570 series
Organic compounds
Carbohydrates or derivatives
536 253, C07H 100, C07H 1500
Patent
active
057672563
DESCRIPTION:
BRIEF SUMMARY
This application is the U.S. national stage entry under 35 U.S.G. 371 of PCT/CA94/00396, filed Jul. 19, 1994.
The requirement to produce pure stereospecific products is the core, pith and marrow of carbohydrate chemistry. Particularly essential is the requirement to produce pure(r) alpha and beta anomers (C-1 anomers in D- and L-sugars). Optimized yield of the compound and proportion of alpha anomer are both highly desirable, as those skilled in the art would appreciate, for practical and commercial reasons.
The present invention primarily relates to a process of providing pure, or significantly higher proportion of alpha anomers in significantly improved yield. Specific donors, acceptors, promoters, and solvents are combined to produce specific anomers. The present invention secondarily provides novel compounds prepared by the process. Although the invention will be described and referred to as it relates to processes of preparation of anomers from specific donors, acceptors, promoters, and solvents, and the resulting anomers, it will be understood that the principles of this invention are equally applicable to similar processes and anomers and accordingly, it will be understood that the invention is not limited to such processes and anomers.
BACKGROUND AND PRIOR ART
The literature teaches the use of various glycosyl donors (sugar residues with a leaving group) with anomeric bromide and other functional groups to build an ultimate di-, tri-, or oligosaccharide.
O-protected beta bromo anomer is converted to the alpha disaccharide in 42% and 65% yield (Lemieux, J. Am. Chem. Soc. 1975, 97, 4056).
Similarly the alpha bromo 1,2-trans peracetyl glycoside anomer is converted to the equivalent beta (1,2-trans) glycoside in 47%, 64%, and 72% yield while the beta acetyl anomer was similarly converted in 71%, 72% and 80% yield (Hanessian, Carbohdr. Res., 53, C13 (1977) and 59, 261 (1977).
Activation of various anomeric donors has been heavily studied, using a variety of promoters. Particularly of interest are those where the alpha:beta product ratio is known and can be improved, and where the overall yield is high.
Previous work from applicant's laboratories has shown that glycosides can be prepared from glycosyl heterocyclic donors without protection of OH groups (S. Hanessian et al. Carbohydrate Res. 80, C17 (1980)). Speculation as to reaction mechanisms suggests metal complex formation with beta 2-pyridylthio donor leaving group, that is the activation is remote to the anomeric carbon, which applicant has termed "remote activation."
Extension of experimentation to a beta perbenzylated glycosyl 2-pyridinecarboxylate donor showed solvent dependence of anomeric product--ether-CH.sub.2 Cl.sub.2 giving primarily alpha while CH.sub.3 CN gave primarily beta. Other extension based on applicant's original work can be found in Tetrahedron, 47, 6435, (1991).
It is a broad object of the invention to prepare specific anomeric compounds in improved yield and proportion, by selection of specific donors, selection of specific acceptors, selection of specific solvents, and selection of specific promoters, in combination underselected specific process conditions. It is an ancillary object of the invention to identify specific donors, suitable for use in the invention. It is another ancillary object of the invention to identify specific acceptors, suitable for use in the invention. It is another ancillary object of the invention to identify specific promoters, suitable for use in the invention. It is another ancillary object of the invention to identify specific solvents, suitable for use in the invention. It is a subsidiary object of the invention to prepare novel anomeric compounds, utilizing unprotected and O-protected glycosyl donors. It is a further subsidiary object of the invention to develop synthetic methods for the synthesis of glycosides, disaccharides, oligosaccharides and nucleosides, using glycosides including but not restricted to pyridyloxy, methoxypyridyloxy, pyrimidyloxy, pyridylcarbonate, and pyridylthiocarbon
REFERENCES:
Hanessian Carbohydrate Research 1980, 80, C17-C22.
Chemical Abstracts, vol. 107, No. 23, 1987, Columbus, Ohio, U.S.; Abstract No. 217957, Nikolaev, A.V., Use of 2-pyridyl 2,3,4,6-tetra-O-benzyl-beta-D-glucoside in the synthesis of 1,2-cis-bonded disaccharides, p. 625.
Tetrahedron, vol. 47, 1991, Vankar, Y.D., Synthesis of beta-O-glycosides, pp. 9985-9992, compound 3 (see Table 1).
Chemistry Letters, Apr. 4, 1994, Mukaiyama, T., Stereoselective synthesis of alpha-ribonucleosides, pp. 557-560.
Chemistry Letters, 1979, Shoda, S. et al. A new method for the synthesis of beta-glucosides, pp. 847-848.
Tetrahedron, vol. 47, 1991, Mereyala, H.B., Stereoselective synthesis of alpha-linked saccharides, pp. 6435-6448.
Tetrahedron, vol. 48, 1992, Garner, P., Synthesis of 2-aminopurine nucleosides, pp. 4259-4270.
Tetrahedron Letters, vol. 32, 1991, Knapp, S., Nucleoside synthesis from thioglycosides, pp. 3627-3630.
LandOfFree
Solution and solid phase stereocontrolled glycosidation does not yet have a rating. At this time, there are no reviews or comments for this patent.
If you have personal experience with Solution and solid phase stereocontrolled glycosidation, we encourage you to share that experience with our LandOfFree.com community. Your opinion is very important and Solution and solid phase stereocontrolled glycosidation will most certainly appreciate the feedback.
Profile ID: LFUS-PAI-O-1727055