Heparan sulfate (HS) and heparin are linear sulfated heteropolysaccharides that consist of alternating a1-4-linked d-glucosamines (GlcN) and 1-4-linked uronic acids, with an a-linkage for l-iduronic acid (IdoA) and a b-linkage for d-glucuronic acid (GlcA). Possible modifications include 2-Osulfation on the uronic acid residues, and one or more modifications on the glucosamine residues, including N-sulfation, N-acetylation, 6-O-sulfation, and 3-O-sulfation. Heparin and low-molecular-weight heparin (LMWH) are the most commonly used anticoagulants or antithrombotic drugs. Compared to HS, heparin has a higher level of sulfation and a higher IdoA content. [1] Heparin is mostly produced by mast cells, and heparan sulfates are produced by different cell types in animals. [2] They are attractive synthetic targets because of the therapeutic application of heparin, and the important roles of HS and heparin in regulating cancer growth, blood coagulation, inflammation, assisting against viral and bacterial infections, signal transduction, lipid metabolism, and cell differentiation. [3] Synthetic heparins can eliminate the side effects caused by inherently heterogeneous heparins purified from natural sources. Their syntheses, however, present great synthetic challenges owing to their structural complexity. Although much progress has been made over the last decade in terms of synthesis, analysis, and understanding of complex HS and heparin, the mechanisms for the formation and regulation of HS/heparin and the structure-function relationship of com-plex HS/heparin are still not fully understood. [2] A tailor-made synthetic process is still lacking.Early chemical syntheses of heparin fragments and analogues [4] required many protection and deprotection steps, making the synthesis of even relatively small oligosaccharides time-consuming and rather inefficient. More recently, various chemical synthetic approaches [5] including target-oriented, [6] modular, [7] combinatorial, [8] one-pot, [9] and solid-phase [10] syntheses, have been developed and used to produce HS/heparin oligosaccharides that range from di-to octasaccharides of different sequences and sulfation patterns. Glycan microarrays have been developed to study heparin/ HS-protein interactions. [11] Nevertheless, the synthesis of HS oligosaccharides of non-repetitive sequences is much more challenging than that of oligosaccharides with repetitive sequences. Synthetic efficiency decreases dramatically as the length of the target molecule increases. Furthermore, variations in the structure and length of the target molecules can completely change the whole synthetic design.Traditional methods of purifying oligosaccharides after enzymatic digestion of GAG chains have provided useful quantities of HS/heparin oligosaccharides for early structureactivity relationship studies. [12] Cloning and characterization of HS biosynthetic enzymes have allowed chemoenzymatic syntheses of various HS/heparin derivatives. [13] Bioactive HS structures that bind to antithrombin, fibroblast gr...