488-41-5

Usage

Originator

Myelobromol,Hormonchemie,W. Germany,1967

Uses

Antineoplastic.

Manufacturing Process

750 g D-mannitol are dissolved in 4,000 ml of a 48% aqueous hydrogenbromide solution, whereupon the solution thus obtained is saturated at 0°Cwith gaseous hydrogen bromide until a HBr content of 69 to 70% is achieved.The reaction mixture is heated for 6 hours at 60°C in an autoclave, is thendecolorized with charcoal, extracted with 1 liter chloroform twice and dilutedwith 7 liters of water. The pH value of the solution is adjusted by means ofsodium bicarbonate to1 to 2. The crystals precipitated after cooling for a dayare filtered and washed with water until free from acid. 250 g crude 1,6-dibromo-1,6-didesoxy-D-mannitol are obtained. MP 176° to 178°C. Analysis:Br % = 52 (calc.: 51.9).250 g of the crude DBM are dissolved in 2.5 liters of hot methanol and ondecolorizing and filtration 2.5 liters of dichloroethane are added. 220 g ofcrystalline DBM are obtained. MP 178°C. Br % = 51.9.

Therapeutic Function

Cancer chemotherapy

General Description

White powder.

Air & Water Reactions

Insoluble in water.

Reactivity Profile

A halogenated alcohol. Flammable and/or toxic gases are generated by the combination of alcohols with alkali metals, nitrides, and strong reducing agents. They react with oxoacids and carboxylic acids to form esters plus water. Oxidizing agents convert them to aldehydes or ketones. Alcohols exhibit both weak acid and weak base behavior. They may initiate the polymerization of isocyanates and epoxides.

Fire Hazard

Flash point data for 1,6-DIBROMO-1,6-DIDEOXY-D-MANNITOL are not available, but 1,6-DIBROMO-1,6-DIDEOXY-D-MANNITOL is probably combustible.

InChI:InChI=1/C6H12Br2O4/c7-1-3(9)5(11)6(12)4(10)2-8/h3-6,9-12H,1-2H2/t3-,4-,5+,6+/m0/s1

Upstream product

• 641-74-7 1,4:3,6-dianhydro-D-mannitol 
• 69-65-8 mannitol 
• 19895-66-0 1,2:5,6-di-anhydro-D-mannitol 
• 17107-32-3 1,6-dibromo-1,6-dideoxy-3,4-O-isopropylidene-D-mannitol 
• 56-23-5 tetrachloromethane 
• 7789-60-8 phosphorus tribromide 
• 506-96-7 Acetyl bromide 

Downstream Products

• 15430-91-8 1,6-Didesoxy-1,6-diiod-D-mannit 
• 226226-31-9 C₈H₁₀O₃ 
• 1069-23-4 (3R,4R)-1,5-hexadiene-3,4-diol 

Relevant academic research and scientific papers

Revisiting Bromohexitols as a Novel Class of Microenvironment-Activated Prodrugs for Cancer Therapy

Bromohexitols represent a potent class of DNA-alkylating carbohydrate chemotherapeutics that has been largely ignored over the last decades due to safety concerns. The limited structure?activity relationship data available reveals significant changes in cytotoxicity with even subtle changes in stereochemistry. However, no attempts have been made to improve the therapeutic window by rational drug design or by using a prodrug approach to exploit differences between tumour physiology and healthy tissue, such as acidic extracellular pH and hypoxia. Herein, we report the photochemical synthesis of highly substituted endoperoxides as key precursors for dibromohexitol derivatives and investigate their use as microenvironment-activated prodrugs for targeting cancer cells. One endoperoxide was identified to have a marked increased activity under hypoxic and low pH conditions, indicating that endoperoxides may serve as microenvironment-activated prodrugs.

A process for preparing dibromo mannitol method

The invention discloses a method for preparing dibromo mannitol method, added in SO42 - /ZrO2 @ GO solid super strong acid catalyst, hydrogen bromide at a relatively low concentration can still be smooth reaction, join the bromide ion in the reaction of the material, can improve the reaction selectivity, catalytic reaction rate, effectively contribute to the reaction, the yield of the lifting dibromo mannitol. The method of the invention low cost, simple operation, safety and environmental protection, easy industrialized application.

A two-bromine mannitol preparation method (by machine translation)

The invention discloses a method of preparing a two-bromine mannitol, added in SO4 2 - /TiO2 ? GO solid super strong acid catalyst, hydrogen bromide at a relatively low concentration can still be smooth reaction, join the bromide ion in the reaction of the material, can improve the reaction selectivity, catalytic reaction rate, effectively contribute to the reaction, the yield of the lifting dibromo mannitol. The method of the invention low cost, simple operation, safety and environmental protection, easy industrialized application. (by machine translation)

Application of cation exchange resin to improvement of yield in bromination reaction of hexanehexol

The invention relates to an application of cation exchange resin to a bromination reaction of hexanehexol. Yield of dibromohexanehexol is substantially increased in the preparation processes of dibromohexanehexol from hexanehexol by using the cation exchange resin, and the effects are obviously better than the effects in the prior art.

Stereoregular poly-O-methyl [m,n]-polyurethanes derived from D-mannitol

Novel linear carbohydrate-derived [m,n]-polyurethanes are successfully prepared using D-mannitol as renewable and low cost starting material. The key comonomer, 1,6-di-O-phenylcarbonyl-2,3,4,5-tetra-O-methyl-D-mannitol is polymerized with a diamine synthesized from D-mannitol or with alkylenediamines. These polymerization reactions afford, respectively, a [6,6]-polyurethane entirely based on a carbohydrate derivative or [m,n]-polyurethanes constituted by a poly-O-methyl substituted unit alternating with a polymethylene chain. All these polymers are stereoregular, as result of the C2 axis of symmetry of mannitol. The optically active polyurethanes are characterized by standard methods (FTIR, RMN, GPC, TGA, and DSC). Thus, GPC analysis reveals weight-average molecular weights between 18,000 and 25,000 Da. Thermal studies (DSC) indicate that the polymers obtained are amorphous materials with T g values dependent on the structure and chain length of the diamine constituent.

Short and efficient synthesis of polyhydroxylated tetrahydrothiophene, tetrahydrothiopyrane and thiepane from bielectrophilic erythro, threo, xylo, ribo, arabino, manno and gluco α,ω-dibromoalditol derivatives

Polyhydroxylated tetrahydrothiophene, tetrahydrothiopyrane and thiepane rings have been readily obtained in excellent yields (78-95%) from thioheterocyclisation of the bielectrophilic peracetylated α,ω-dibrominated derivatives of tetritols (erythritol (1) and d,L-threitol (4)), pentitols (xylitol (7), ribitol (10) and D-arabinitol (14)) and hexitols (D-mannitol (17) and D-glucitol (20)), respectively. With 2,3,4,5-tetra-O-acetyl-1,6-dibromo-1,6-dideoxy-D-glucitol (21) as substrate, the unexpected 2,6-anhydro derivative 25 was obtained. This could be attributed to previous S= regioselective nucleophilic attack at C-1 position followed by 1,2-transesterification and 2,6-O-heterocyclisation. The preferential attack at C-1 of the D-glucitol derivative 21 subsequently allowed a facile direct synthesis in good yields of 2,3,4,5,6-penta-O-acetyl-1-bromo-1-deoxy-D-glucitol (26), 2,3,4,5-tetra-O-acetyl-6-bromo-6-deoxy-1-thiobutyl-1-deoxy-D-glucitol (28) and 2,3,4,5-tetra-O-acetyl-6-bromo-6-deoxy-1-thiooctyl-1-deoxy-D-glucitol (28).

Total synthesis of 3-deoxy-D-manno-2-octulosonic acid (KDO) and 2-deoxy-β-KDO

(equation presented) Total syntheses of KDO and 2-deoxy-β-KDO are reported. The C2-symmetric dienediol 4 was desymmetrized by conversion to its corresponding 1,4-dioxanone 5. Ireland-Claisen rearrangement of 5 provided the 6-vinyldihydropyran-2-carboxylate template 6. Double-Sharpless asymmetric dihydroxylation gave the tetraol 7a, which was converted to KDO and 2-deoxy-β-KDO using methods similar to those previously reported. This synthetic scheme provides a flexible route to KDO and KDO analogues.

2,5:3,4-DIANHYDRO-1,6-DIDEOXY-6-(TRIMETHYLAMINO)-D-ALLITOL AND -D-GALACTITOL

A new, four-step synthesis of 2,5:3,6-dianhydro-1-deoxy-D-glucitol 16 was worked out, starting from 1,6-dibromo-1,6-dideoxy-D-mannitol.Compound 16 was converted into different 4-O-acyl derivatives, the 3,6-anhydro rings of which where opened with hydrogen bromide, yielding the corresponding 6-bromo compounds.These were converted, via the 6-azides, into the 6-(dimethylamino) derivatives, the sulfonic esters of which gave, on treatment with base, the 2,5:3,4-dianhydro-D-allitol and -D-galactitol derivatives.These were converted with methyl iodide into the corresponding quaternary salts.On biological testing, only the D-allitol derivative showed weak, muscarine-like activity.