99748-10-4

Upstream product

• 65827-58-9 1,2,4,6-tetra-O-acetyl-3-O-benzyl-α-D-mannopyranoside 
• 65877-60-3 1,2,4,6-tetra-O-acetyl-α-D-mannopyranose 
• 7693-46-1 4-Nitrophenyl chloroformate 
• 530-26-7 D-Mannose 
• 3458-28-4 D-Mannose 
• 93714-01-3 methyl 3-O-benzyl-α-D-mannopyranoside 
• 3162-96-7 methyl-4,6-O-phenylmethylene-α-D-mannopyranoside 
• 2774-19-8 (2R,4aR,6S,7S,8R,8aR)-8-Benzyloxy-6-methoxy-2-phenyl-hexahydro-pyrano[3,2-d][1,3]dioxin-7-ol 
• 617-04-9 (2R,3S,4S,5S,6S)-2-(hydroxymethyl)-6-methoxytetrahydro-2H-pyran-3,4,5-triol 

Downstream Products

• 1266609-51-1 1,3,4,5-tetra-O-benzyl-2-O-(2,4,6-tri-O-acetyl-3-O-carbamoyl-α-D-mannopyranosyl)-β-L-gulopyranoside 
• 1266609-55-5 (2R,3R,4S,5S,6R)-2-(acetoxymethyl)-4-(carbamoyloxy)-6-(((2R,3S,4S,5R,6S)-4,5-diacetoxy-6-(acetoxymethyl)-2-(2-(2-(((benzyloxy)carbonyl)amino)ethoxy)ethoxy)tetrahydro-2H-pyran-3-yl)oxy)tetrahydro-2H-pyran-3,5-diyl diacetate 
• 162111-91-3 3,4,6-tetra-O-acetyl-2-O-(2,4,6-tri-O-acetyl-3-O-carbamoyl-α-D-mannopyranosyl)-α-L-gulopyranosyl diphenylphosphate 
• 162153-19-7 1,3,4,6-tetra-O-benzyl-2-O-(2,4,6-tri-O-acetyl-3-O-carbamoyl-α-D-mannopyranosyl)-β-L-gulopyranoside 
• 162111-85-5 diphenylphosphoryl-2,4,6-tri-O-acetyl-3-O-carbamoyl-α-D-mannopyranoside 
• 217180-23-9 Acetic acid (2R,3S,4S,5R,6R)-5-acetoxy-6-acetoxymethyl-2-[(2R,3S,4S,5R,6S)-6-acetoxymethyl-4,5-bis-benzyloxy-2-(2,2,2-trichloro-acetimidoyloxy)-tetrahydro-pyran-3-yloxy]-4-carbamoyloxy-tetrahydro-pyran-3-yl ester 
• 217180-22-8 6-O-acetyl-3,4-di-O-benzyl-2-O-(2,4,6-tri-O-acetyl-3-O-carbamoyl-α-D-mannopyranosyl)-α/β-gulopyranoside 
• 102871-16-9 1,6-di-O-acetyl-3,4-di-O-benzyl-2-O-(2,4,6-tri-O-acetyl-3-O-carbamoyl-α-D-mannopyranosyl)-L-gulopyranose 

Relevant academic research and scientific papers

Multi-gram scale synthesis of a bleomycin (BLM) carbohydrate moiety: exploring the antitumor beneficial effect of BLM disaccharide attached to 10-hydroxycamptothecine (10-HCPT)

The “tumor-seeking” role of bleomycin (BLM) disaccharide has been demonstrated to serve as a promising tool for cancer diagnosis and a potential ligand for targeted therapy. However, these practical applications are often hampered by the lack of BLM disaccharide. Herein, an efficient multi-gram synthesis of peracetylated BLM disaccharide 20 is achieved by a TMSOTF-mediated glycosidation coupling manner in 43.6% overall yield in terms of benzyl galactoside. The critical innovation of the synthetic strategy is that inexpensive benzyl galactoside was first adopted to prepare an l-gulose subunit 3 as a glycosyl acceptor, with a much shorter route in 73.0% yield, and a 3-O-carbamoyl-mannose donor 4 was achieved in 47.2% yield by lowering the amount of dibutyltin oxide, and merging aminolysis and selective deacetylation into a one-pot reaction. Next, the incorporation of BLM disaccharide into 10-hydroxycamptothecin (10-HCPT), a non-specific model compound, to form conjugate 1 could significantly improve the antitumor activity and display obvious selectivity toward cancerous and normal cells in comparison with 10-HCPT. Moreover, BLM disaccharide itself was non-cytotoxic, clearly indicating the importance and potential of BLM disaccharide in solving the targeted antitumor therapy of cytotoxic drugs.

Preparation methods of 2-hydroxygulose receptor derivative, bleomycin disaccharide and precursor of bleomycin disaccharide

The invention discloses a preparation method of a 2-hydroxygulose receptor derivative. The method comprises the following steps: carrying out a series of reactions of ylidene protection on benzyl-beta-galactoside, 3-position configuration inversion, deacetylation, and selective acetylation. Meanwhile, the invention also discloses a method for preparing bleomycin disaccharide and a precursor of bleomycin disaccharide by using the 2-hydroxygulose receptor derivative prepared by the method as a receptor. According to the invention, through the adoption of the preparation method of the 2-hydroxygulose receptor derivative, the problems that sources of natural L-gulose are rare, cost is too high, and industrialization is not facilitated and the like are solved; meanwhile, the problems that the bleomycin disaccharide and the precursor of the bleomycin disaccharide are low in yield, reaction operability and repeatability are poor, industrialization is not facilitated and the like are solved. The preparation methods have the advantages that raw materials are cheap and easily available, the yield is high, the operability is high, conditions can be easily controlled, industrial amplificationcan be realized, efficiency is high, cost is low, and the like.

SUGAR-LINKER-DRUG CONJUGATES

The present disclosure relates to sugar-linker-drug conjugates, of the formula [A-B-]n-L-D, wherein A is a saccharide; B is a spacer, n is an integer selected from 1 to 3; L is a linker group and D is a drug having a chemically reactive functional group selected from the group consisting of a primary or secondary amine, hydroxyl, sulfhydryl, carboxyl, aldehyde and ketone. Pharmaceutical compositions comprising the conjugates and methods of using thern are also provided.

SACCHARIDE CONJUGATES

This invention relates to compounds comprising a saccharide conjugated to an imaging agent or a reporter group, compositions comprising them and methods of using them. Specifically BLM-disaccharide and BLM-monosaccharide conjugates containing different linker groups and an imaging agent or a reporter group are provided for the targeting and imaging of tumors.

CARBOHYDRATE-MEDIATED TUMOR TARGETING

Tumors can be selectively targeted via compounds provided herein according to the formula, or a pharmaceutically acceptable salt thereof, wherein RA and RB are as defined herein. Tumors can be imaged or targeted for therapeutic treat

Total synthesis of bleomycin A2 and related agents. 4. Synthesis of the disaccharide subunit: 2-O-( 3-O-Carbamoyl-α-D-mannopyranosyl)-L-gulopyranose and completion of the total synthesis of bleomycin A2

The chemical synthesis of 2-O-(3-O-carbamoyl-α-D-mannopyranosyl)-L-gulopyranose and its incorporation into a total synthesis of bleomycin A2 (1) readily adaptable to the preparation of structural analogs are detailed. Key strategic elements of

Synthesis of the Carbohydrate Moiety of Bleomycin. 2,3,4,6-Tetra-O-substituted D-Mannose Derivatives

As part of the synthesis of the carbohydrate moiety of bleomycin , two different approaches were employed for the synthesis of appropriate 3-O-carbamoylmannose precursors.One approach, which required