Orthogonally protected disaccharide building blocks for...

Organic compounds -- part of the class 532-570 series – Organic compounds – Carbohydrates or derivatives

Reexamination Certificate

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Reexamination Certificate

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07655769

ABSTRACT:
Orthogonally protected disaccharide building blocks for synthesis of heparin saccharide are disclosed. The disaccharide building block has a formula (I), in which L is a leaving group, P1, P2, P3and P4are different, and of them P1is an ester-type protecting group, P2is a hydroxyl protecting group that could be oxidized to a carboxylic acid, P3is a hydroxyl protecting group, and P4is a hydroxyl protecting group which allows chemoselective deprotection with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). Acting as an elongation unit, the disaccharide building block of formula (I) may react with a starting unit of formula (II) to synthesize a heparin saccharide of desired size.

REFERENCES:
O'Neil et al. (eds.), The Merck Index, An Encyclopedia of Chemicals, Drugs, and Biologicals, 13th Editions, 2001, Merck & Co., Whitehouse Station, NJ, only pp. 830-831 supplied, see entry 4670 (“Heparin”).
Tabeur et al., “L-Iduronic Acid Derivatives as GLycosyl Donors,” Carbohydrate Research, 281(2), 253-276 (1996).
Noti et al., “Preparation and Use of Microarrays Containing Synthetic Heparin Oligosaccharides for the Rapid Analysis of Heparin-Protein Interacitons,” Chemistry: A European Journal, 12(34), 8664-8686 (2006).
Lohman et al., “A Sterochemical Surprise at the Late Stage of the Synthesis of a Fully N-Differentiated Heparin Oligosaccharides Containing Amino, Acetamido, and N-Sulfonate Groups,” Journal of Organic Chemistry, 69(12), 4081-4093 (2004).
Yu et al., “Novel Efficient Routes to Heparin Monosaccharides and Disaccharides Achived via Regio- and Stereoselective Glycosidation,” Organic Letters, 6(5), 723-726 .(2004).
Tabeur et al, “L-iduronic acid derivatives as glycosyl donors,” Carohydr. Res. 23;281(2)253-76.
Hirsh et al,, “Guide to Anticoagulant Therapy: Heparin: A Statement for Healthcare Professionals From The American the American Heart Association,” Circulation, Jun. 19, 2001;103(24)2994-3018.
Lee et al, “Synthesis of Heparin Oligosaccharides,” J. Am Chem. Soc, 126:476-477 (2004) Publication Date Dec. 19, 2003, Plus Supplemental Information.

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