Classifications

• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
  • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
  • C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
  • C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
  • C07H1/00—Processes for the preparation of sugar derivatives
• • C—CHEMISTRY; METALLURGY
  • C07—ORGANIC CHEMISTRY
  • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
  • C07H13/00—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids
  • C07H13/02—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids
  • C07H13/04—Compounds containing saccharide radicals esterified by carbonic acid or derivatives thereof, or by organic acids, e.g. phosphonic acids by carboxylic acids having the esterifying carboxyl radicals attached to acyclic carbon atoms
• • C—CHEMISTRY; METALLURGY
  • C13—SUGAR INDUSTRY
  • C13K—SACCHARIDES OBTAINED FROM NATURAL SOURCES OR BY HYDROLYSIS OF NATURALLY OCCURRING DISACCHARIDES, OLIGOSACCHARIDES OR POLYSACCHARIDES
  • C13K13/00—Sugars not otherwise provided for in this class

Definitions

• the present invention relates methods of making sucralose.
• Sucralose (4,1 ',6'-chloro-4,1 ',6'-trideoxygalactosucrose) is a non-calorie sweetner that is produced by selective chlorination of sucrose. It is 400-600 times as sweet as sucrose and provides a clean sweet taste that does not leave an unpleasant aftertaste. Its exceptional heat stability makes sucralose a promisinig sugar substitute in preparing low- or non-calorie food and beverages. [0004] Synthesis of sucralose from sucrose requires chlorination at A-, 1 '- and 6'- positions of sucrose.
• sucralose-6-ester Two primary hydroxyl groups (V and 6') and one secondary hydroxyl group (4-) need to be replaced with chlorine while the third primary hydroxyl group (6-) is unaffected. Therefore, one route to synthesize sucralose is to first protect the 6- hydroxyl group via esterification to generate sucrose-6-ester, convert the partly protected sucrose to sucralose-6-ester by selective chlorination under certain
• sucrose-6-ester comprises formation of a sucrose alkyl 4,6-orthoester which is hydrolized to generate a mixture of 4- and 6- monoesters of sucrose.
• the sucrose-4-ester is then converted to sucrose-6-ester under basic conditions (US Patent No. 5,440,026).
• Sucrose-6-ester can also be prepared via tin-mediated reactions.
• Acetic anhydride is used as esterifying agent and dibutyl tin as catalyst.
• a method for the synthesis of a sucrose 6-ester comprising reacting a mixture comprising sucrose, an ester and an organic solvent with a solid super acid catalyst for a period of time and at a temperature sufficient to produce sucrose 6-ester, wherein the ester comprises ethyl acetate, the organic solvent comprises DMF and wherein the solid super acid comprises SO 4 2- -TiO 2 ZAI 2 O 3 .
• a method for the synthesis of a sucrose 6-ester comprising reacting a mixture comprising sucrose, an ester and an organic solvent with a solid super acid catalyst for a period of time and at a temperature sufficient to produce sucrose 6-ester, wherein the
• ester comprises ethyl acetate
• the organic solvent comprises DMF
• the solid super acid comprises SO 4 2" --TiO 2 .
• a process for the synthesis of sucrose-6-ester from sucrose comprises reacting a mixture comprising sucrose, an ester and an organic solvent with a solid super acid catalyst for a period of time and at a temperature sufficient to produce sucrose-6-ester.
• the catalyst is then filtered and can be reused for the same reaction.
• the ester is distilled to afford a mixture comprising sucrose-6-ester and the organic solvent. If the organic solvent is one that is compatible for the chlorination reation, the obtained sucrose-6-ester solution can be used for the next step in sucralose synthesis without further purification.
• the choice of organic solvents is determined by the solubility of the sucrose and the ester in the solvents, as well as the safety and toxicity considerations, especially if the sucrose-6-ester is to be used for the syntheis of sucralose, a food additive. Another consideration that should be taken into account in selecting a solvent is whether the solvent is suitable for the next step in sucralose synthesis, the chlorination reaction.
• the solvent is preferably a polar inorganic solvent.
• the polar organic solvent is preferably N,N-dimethylformamide (DMF) as DMF is a suitable solvent for the chlorination reaction.
• DMF N,N-dimethylformamide
• sucrose-6-ester can be used directly for chlorination reaction without further purification.
• the amount of the organic solvent to be used may be determined by the above-mentioned solubility considerations.
• the polar solvent is DMF, it is preferably used in an amount of approximately 5 mL/g sucrose.
• the ester is preferably ethyl acetate (EtOAc).
• the amount of the ester to be used will be determined to facilitate the conversion of the desired sucrose-6-ester and suppress the formation of outgrowth.
• the ester is EtOAc, it is preferably used in an amount of from 5 to 12 mol/mol sucrose.
• the solid super acid catalyst may be selected from a group consists of one or a mixture of sulfated oxide of an element selected from those of group 3, group 4, group 5, group 6, group 7, group 8 group 9, group 10, group 1 1 , group 12, group 13, group 14, group 15 and those of the series of lanthanides, alone or combined with each other.
• solid super acid catalyst examples include SO 4 2" -TiO 2 /AI 2 O 3 , SO 4 2" - Fe 2 O 3 ZAI 2 O 3 , SO 4 2" -ZnO/AI 2 O 3 , SO 4 2" -CeO 2 /AI 2 O 3 , SO 4 2" -ZrO 2 /AI 2 O 3 , SO 4 2" ⁇ TiO 2 /AI 2 O 3 or SO 4 2" ⁇ TiO 2 , and the more preferable catalysts are SO 4 2" ⁇ TiO 2 /AI 2 O 3 and SO 4 2" - TiO 2 .
• the catalyst may be SO 4 2" ⁇ TiO 2 /AI 2 O 3 , AI 2 O 3 infused in titanous sulfate solution and then calcinated to generate SO 4 2" ⁇ TiO 2 /AI 2 O 3 solid super acid.
• SO 4 2" ⁇ TiO 2 solid super acid may be prepared by titanous sulfate calcinations.
• a one-step synthesis of sucrose-6- acetate comprises selective esterification with EtOAc at the 6- position of sucrose in the presence of solid super acid such as SO 4 2- -TiO 2 ZAI 2 O 3 or SO 4 2" ⁇ TiO 2 .
• solid super acid such as SO 4 2- -TiO 2 ZAI 2 O 3 or SO 4 2" ⁇ TiO 2 .
• Acetate syrup (40 g, contained 22g/0.05 mol of sucralose 6-acetate), which was prepared in example 2, was added to acetic anhydride (100 ml_, 1.05 mol). Pyridine (2 ml_) was added thereto and the reaction was stirred at 50 0 C for 3 h. The reaction mixture was then cooled to 20 0 C. Methanol (60 ml_) was added dropwise to maintain the reaction temperature below 50 0 C. The mixture was distilled at a temperature below 60 0 C under reduced pressure to get TGSPA syrup. The obtained syrup was dissolved in toluene (300 ml_) and washed by brine (50 ml_).
• the combined organic phase was distilled to TGSPA concentrated syrup under reduced pressure at a temperature below 60 0 C.
• the obtained syrup was dissolved in toluene (40 ml_) at 70 0 C and cooled to room temperature for recrystallization.
• the crystals were filtered recrystallized two more times to yield about 26 g pure TGSPA (0.42 mol, 85% yield).
• TGSPA (10 g, 0.016 mol) was dissolved in methanol (100 ml_) and cooled to 15 0 C. 20% Sodium methoxide/methanol solution (4 g, 0.015 mol) was added thereto and stirred for 5 h at room temperature. After the reaction was complete it was neutralized and filtered by hydrogen strong acid ion exchange resin, which was consequently washed by methanol (2x50 ml_). The filtrate was distilled to soft foam under reduced pressure below 30 0 C. The foam was dissolved in distilled water (100

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• Saccharide Compounds (AREA)
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• Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
• Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

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• 2006
  • 2006-10-25 US US11/552,813 patent/US20080103295A1/en not_active Abandoned
• 2007
  • 2007-10-19 TW TW096139366A patent/TW200833707A/zh unknown
  • 2007-10-24 CA CA002667366A patent/CA2667366A1/en not_active Abandoned
  • 2007-10-24 EP EP07854399A patent/EP2097432A4/en not_active Withdrawn
  • 2007-10-24 JP JP2009534842A patent/JP2010508286A/ja active Pending
  • 2007-10-24 CN CNA2007800436663A patent/CN101558076A/zh active Pending
  • 2007-10-24 BR BRPI0718058-6A2A patent/BRPI0718058A2/pt not_active IP Right Cessation
  • 2007-10-24 RU RU2009119517/04A patent/RU2009119517A/ru not_active Application Discontinuation
  • 2007-10-24 KR KR1020097010473A patent/KR20090082421A/ko not_active Withdrawn
  • 2007-10-24 WO PCT/US2007/082424 patent/WO2008052077A2/en not_active Ceased
  • 2007-10-24 AU AU2007308948A patent/AU2007308948A1/en not_active Abandoned
  • 2007-10-24 MX MX2009004356A patent/MX2009004356A/es not_active Application Discontinuation

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