Spaced heparinoids: a new class of heparin-like molcules

A process for the preparation of spaced heparinoids of Formulas 1 and 2,

• wherein
• S1, S2, S3, S4, and S5 are independently selected from the group comprising:
• wherein L1, L2, and L3 are independently selected from the group consisting of —CO(CH2)aCO—;
• —CO(CH2)bNHCO—;
• —CONH(CH2)cCO—;
• —CONH(CH2)dNHCO—;
• —CO(CH2)eNHCO(CH2)fCONH(CH2)gCO—;
• X is —N3, —NH—, —NH2, —NHAc, —NHSO3Na, or —NCO;
• Y is —OH, —OMe, —OCH2CF3, or C5-C10-OAryl;
• R1 is —H, —CH2OH or C1-C10 Alkyl;
• R2 is Bn or PMB;
• R3 is C1-C10 Acyl or Bz;
• and R4 is —COOH or —COONa;
• and subscripts ‘a’, ‘b’, ‘c’, ‘d’, ‘e’, ‘f’, and ‘g’ independently vary from 1-10, and wherein the steps comprising:
• (a) preparing the trichloroacetimidates of azidosaccharides as described in paragraph [0032];
• (b) glycosylating the acetimidate derivatives of the azidosaccharides in Step ‘a’ as described in the specification, paragraph [0032];
• (c) reducing the azide in Step ‘b’ to the corresponding mine using either Zn/ammonium chloride or triphenylphosphine as described in paragraphs [0034] or [0035] respectively;
• (d) reacting the amino sugars in Step ‘c’ with disuccinimidyl carbonate as described in paragraph;
• [0036];
• (e) reacting the saccharide isocyanates in Step ‘d’ with diamines as described in paragraph;
• [0037];
• (f) reacting the saccharides-amine in Step ‘e’ with t-Boc protected amino acid NHS-ester (linker) as described in paragraph [0038];
• (g) removing the t-Boc protected saccharides in Step ‘f’ with 3N HCl/MeOH as described in paragraph [0039];
• (h) globally deacetylating the saccharides in Step ‘g’ with NaOMe/MeOH as described in paragraph [0040];
• (i) reacting the amino sugars in Step ‘i’ with disuccinimidyl suberate as described in paragraph;
• [0041];
• and
• (j) O-sulfonating or N-sulfonating the oligosaccharides in Step ‘i’ with pyrdine-sulfur trioxide complex as described in paragraphs [0042] and [0043] respectively.