TW201040152A - Method for preparing ascorbic acid derivatives - Google Patents
Method for preparing ascorbic acid derivatives Download PDFInfo
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- TW201040152A TW201040152A TW099114348A TW99114348A TW201040152A TW 201040152 A TW201040152 A TW 201040152A TW 099114348 A TW099114348 A TW 099114348A TW 99114348 A TW99114348 A TW 99114348A TW 201040152 A TW201040152 A TW 201040152A
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/02—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings
- C07D307/34—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D307/56—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D307/62—Three oxygen atoms, e.g. ascorbic acid
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/34—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide
- A61K31/341—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having five-membered rings with one oxygen as the only ring hetero atom, e.g. isosorbide not condensed with another ring, e.g. ranitidine, furosemide, bufetolol, muscarine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
Abstract
Description
COSM-02564TW 201040152 六、發明說明： 【發明所屬之技術頜域】 以下揭露係關於一種製備3_〇'經取代之抗壞血酸之方法’特定 言之，為-種增加反應速率及提高產f之新穎方法。 【先前技術】 L-抗壞血酸為-種具有抗氧化劑功能之物質，且已經使用於各 種領域中（例如化妝品及藥劑），特定言之，係用於抑制黑色素 〇 累積。當抗壞血酸使用於食物中時，抗壞血酸之膠原蛋白-生物合 成作用及促進生長作用可避免褐變反應（browning)、保持風味、 以及維持新鮮。 然而，抗壞血酸在空氣中易因熱、光、以及氧氣而氧化。特定 言之，在含水相中，會促進抗壞血酸之氧化及分解。因此’當抗 每血酸使用在藥劑、化妝品、以及食物等中時，在製造及長時間 諸存的過程中可能發生效度（titer )降低及變色。 q 為了解決這些問題，已研究出抗壞血酸之3號位置上之〇H基 圈經低碳數烷基基團取代之化合物。用以製造這些化合物之方法 係揭露於文獻中，例如美國專利第4,552,888號’及J. Med. Chem.， 43, 450 ( 1965 )及 Can, J. Chem·, 31, 793 ( 1988)，其中抗壞血酸 及甲醇鈉（NaOMe )係在作為溶劑之二甲亞石風（dimethyl sulfoxide， 〇Ms〇)及二曱基甲醯胺（dimethyl formamide，DMF)中反應以 #到抗壞血酸鈉，接著使抗壞血酸鈉與烷基鹵化物反應。 然而’該方法在抗壞血酸之3號位置上引入烷基基團有所限制， 足會製造許多副產物。COSM-02564TW 201040152 VI. Description of the invention: [Technology of the jaw region of the invention] The following disclosure relates to a method for preparing 3_〇'-substituted ascorbic acid, which is specifically described as a method for increasing the reaction rate and improving the yield of f method. [Prior Art] L-ascorbic acid is a substance having an antioxidant function and has been used in various fields (e.g., cosmetics and pharmaceuticals), specifically, for inhibiting melanin 累积 accumulation. When ascorbic acid is used in food, the collagen-biosynthesis and growth-promoting effects of ascorbic acid avoid browning, maintain flavor, and maintain freshness. However, ascorbic acid is easily oxidized in the air by heat, light, and oxygen. In particular, in the aqueous phase, oxidation and decomposition of ascorbic acid are promoted. Therefore, when anti-peracid is used in pharmaceuticals, cosmetics, foods, and the like, titer reduction and discoloration may occur during manufacture and long-term survival. q In order to solve these problems, a compound in which the hydrazine H ring of the ascorbic acid at the position 3 is substituted with a lower alkyl group has been studied. Methods for making these compounds are disclosed in the literature, for example, in U.S. Patent No. 4,552,888, and J. Med. Chem., 43, 450 (1965) and Can, J. Chem., 31, 793 (1988), Ascorbic acid and sodium methoxide (NaOMe) are reacted in a solvent of dimethyl sulfoxide (〇Ms〇) and dimethyl formamide (DMF) to #to ascorbate, followed by sodium ascorbate Reacts with an alkyl halide. However, this method has a limitation in introducing an alkyl group at the position 3 of ascorbic acid, and it is sufficient to produce many by-products.
201040152 COSM-02564TW 此外’由於二甲亞砜（DMSO)及二曱基甲醯胺（DMF)具有 @彿點’且3號位置經取代之抗壞血酸在質子性（protic)溶劑中 具有高溶解度’故難以純化所得之抗壞血酸。在許多情形下，在 純化中應使用管柱層析法 (column chromatography)。因此，產 也非g低且難以建立一具成本效益之製程。 為了解決這些問題’日本專利公開申請案第1983-57373號係揭 種方法’在第一步驟中’以亞異丙基保護抗壞血酸上之5號 0 〜位置上之0Η基團’以合成5,6-0-亞異丙基抗壞血酸作為前 驅物· A $ - h ，社弟二步驟中，使該5,6-0-亞異丙基抗壞血酸與烷基鹵化 物反應以得到3-〇_烷基-5,6-0-亞異丙基抗壞血酸；而在第三步驟 ’該保護基團係藉由水解作用自3-0-烷基-5,6-0-亞異丙基抗壞 血^移除’且在5號及6號位置上再次生成〇H基團，以得到3-0-貌基抗壞血酸。然而，因為在第三步驟中使用高度質子性溶劑， 故該方法具有整體產率下降之缺點。 本案申請人亦已開發出各種具有高產率之方法，而這些方法係 〇 敘述於韓國專利第10-0761959、10-0500503、以及10-0548989號 中。 4而’本案申請人所敘述的這些方法雖然具有良好轉化率，但 具有反應時間過久之缺點。該等方法同時具有難以自產物中移除 雜處之缺點，因而純化成本居高不下。 本案申請人已研究來解決由其所開發之方法中的限制，且藉由 開發一種透過簡單過程用以縮短反應時間及降低純化成本之新穎 方法來完成本發明。 4201040152 COSM-02564TW In addition, 'as dimethyl sulfoxide (DMSO) and dimethyl carbamide (DMF) have @佛点' and the ascorbic acid substituted at position 3 has high solubility in protic solvents' It is difficult to purify the obtained ascorbic acid. In many cases, column chromatography should be used in the purification. Therefore, production is not low and it is difficult to establish a cost-effective process. In order to solve these problems, Japanese Patent Application Laid-Open No. 1983-57373 discloses a method of 'protecting 5' in the first step by protecting the 0 Η group at the 5th position of the ascorbic acid by isopropylidene in the first step. 6-0-isopropylidene ascorbic acid as a precursor · A $ - h, in the second step of the process, the 5,6-0-isopropylidene ascorbic acid is reacted with an alkyl halide to obtain 3-anthracene Base-5,6-0-isopropylidene ascorbic acid; and in the third step 'the protecting group is hydrolyzed from 3-0-alkyl-5,6-0-isopropylidene ascorbic acid ^Remove' and regenerate the 〇H group at positions 5 and 6 to obtain 3-0-formyl ascorbic acid. However, since a highly protic solvent is used in the third step, the method has the disadvantage of a decrease in overall yield. Applicants of the present invention have also developed various methods of high yield, and these methods are described in Korean Patent Nos. 10-0761959, 10-0500503, and 10-0548989. 4 While the methods described by the applicant of the present invention have a good conversion rate, they have the disadvantage of being too late in reaction time. These methods have the disadvantage of being difficult to remove impurities from the product, and thus the purification cost is high. The applicant of the present invention has studied to solve the limitations in the method developed thereby, and has completed the present invention by developing a novel method for shortening the reaction time and reducing the purification cost by a simple process. 4
201040152 COSM-02564TW 【發明内容】 <技術問題> 本發明之目的係提供一種製備3-0經取代之抗壞血酸之方法， 其能夠明顯地增加反應速率及提高產率、且降低純化成本。本案 申請人已努力達到上述目的，並因而發現這些目的可藉由簡單方 法達到。 【實施方式】 下文，將以所附圖式詳細描述例示實施態樣。 ❹ 本發明係關於一種製備由化學式I所示之3-0-烷基-經取代之抗 壞血酸之方法，包括： a) 以醯基保護抗壞血酸中之5,6-二羥基，如流程圖I ; b ) 於一驗性化合物存在下，藉由一介面反應 (interfacial-reaction)，使5,6-二驢基經保護之抗壞血酸與 烧基lS化物反應；以及 c) 去保護所得之3-0-烷基-5,6-0-二醯基抗壞血酸： Q [化學式I]201040152 COSM-02564TW SUMMARY OF THE INVENTION <Technical Problem> An object of the present invention is to provide a process for producing 3-0 substituted ascorbic acid which can significantly increase the reaction rate and increase the yield, and reduce the purification cost. The applicant in this case has worked hard to achieve the above objectives and has thus found that these objectives can be achieved by a simple method. [Embodiment] Hereinafter, embodiments will be exemplified in detail with reference to the accompanying drawings. The present invention relates to a process for the preparation of 3-0-alkyl-substituted ascorbic acid of formula I, comprising: a) protecting the 5,6-dihydroxy group of ascorbic acid with a thiol group, as in Scheme I; b) reacting 5,6-dimercaptoprotected ascorbic acid with a burnt lS compound by an interfacial-reaction in the presence of an inert compound; and c) deprotecting the resulting 3-0 -alkyl-5,6-0-dimercapto ascorbic acid: Q [Chemical Formula I]
(其中R為C1至C7烷基基團）(wherein R is a C1 to C7 alkyl group)
201040152 COSM-02564TW201040152 COSM-02564TW
[流程圖i][Flowchart i]
201040152 COSM-02564TW201040152 COSM-02564TW
m 八句國系签图 Ο 卜丁、史日 (其中R為Cl至C7烷基基 至C4烧基基團或苯基基團其中之一）。 在此方法中，在以醯基鹵化物保護抗壞血酸之5號及6號位置 上之羥基中，相較於韓國專利第10_0761959號（其為本案申請人 之先前申請案）中所敘述之以乙縮醛的保護，此方法中之反應速 率係增加大約50%或更多。因此，本發明具有在整體過程中可縮 短反應時間之優點。舉例言之，當根據本發明之方法使用酿基齒 化物時，定量地（quantitativeb〇保護抗 〇 團費時大崎時。另-方面，捕目彻_^ = 法中使用乙祕保護該基團則費時5小時（實施例…使用酿基 豳化物保護為本發明之—重要特徵，藉以增加保護過程中之反應 速率’且可因此提高產量。另外，由於使賴基㈣物的保護合 增加疏水性，故在步驟b)之3_〇•醯化反應之過程令，雜質^ 如副產物及驗）在-含水層中係_地溶解及分離。因此，僅有 作為產物之3_0_絲_5,6_〇_二縣抗壞血酸會溶解在-有機溶劑 層中’且可簡單地分離及純仆兮 电化該產物0因此，此方法係提供-種 能夠在製備過程令簡單地分離甚私+丈 " 早刀離產物之手段。在此方法中，每—成 6m Eight-country signature Ο Bu Ding, Shi Ri (where R is a Cl to C7 alkyl group to one of a C4 alkyl group or a phenyl group). In this method, in the hydroxyl group at positions 5 and 6 which protects ascorbic acid with a mercapto halide, it is described in Korean Patent No. 10_0761959 (which is the prior application of the applicant) The protection of the acetal, the reaction rate in this method is increased by about 50% or more. Therefore, the present invention has the advantage that the reaction time can be shortened in the overall process. For example, when the brewing base toothing is used according to the method of the present invention, quantitatively (protective b〇 protects the anti-small group from time-consuming Osaki. On the other hand, the use of the secretory _^ = method to protect the group It takes 5 hours (Example...protection using the thiolated hydrazine as an important feature of the invention, thereby increasing the reaction rate in the protection process' and thus increasing the yield. In addition, the hydrophobicity of the lysine (tetra) is increased due to the hydrophobicity. Sex, so in the process of step 3), the process of the deuteration reaction, such as impurities, such as by-products and tests, is dissolved and separated in the aquifer. Therefore, only 3_0_丝_5,6_〇_二县ascorbic acid as a product will be dissolved in the -organic solvent layer' and can be easily separated and purely electrochemically oxidized. Therefore, this method provides Being able to simply separate the very private + Zhang " early knife away from the product during the preparation process. In this method, each into 6
201040152 COSM-02564TW 分係以相同速率反應，但若需要的話，使用一過量之成分可導致 更有效之純化及更高之產率。如此修飾均在熟悉此項技術之人士 所理解之範圍内，而細節於此毋需贅述。 在步驟a)中所使用之有機溶劑之例子係包括任何非質子性溶 劑’且較佳之有機溶劑為使用例如丙酮、乙醚、戊烷、己烷、以 及庚烧。醯基_化物之例子包括’但不限於，氯化乙醯（acetyl chloride )及苯甲醯氣（benzoyl chloride )。保護步驟中之反應溫度 係介於室溫及50°C之間，較佳為30至50。(：，及反應時間為0.5 〇 至3小時，較佳為1至2小時。可在如此溫度及時間下達到該定 量保護。該保護一般係在相同速率下實施。然而，使用1至10% 之過量醯基鹵化物可使產率增加且可採用熟悉此項技術之人士所 進行之一般反應。 步驟b)係在一含水層及一有機層之雙層中藉由介面反應達到。 首先，5,6-二酿基抗壞血酸及驗（例如KHC03)係溶解於該含水 層中。接著，加入烧基鹵化物至該有機溶劑層（例如乙酸乙酯及 Q 乙醚）中。該有機溶劑係在高溫下回流以製造3-0-烷基-5,6-0-二 醯基抗壞血酸。回流溫度可根據所使用之溶劑而適當地選擇。所 製得之3-0-烷基-5,6-0-二醯基抗壞血酸係溶解在該有機層中，而 當反應繼續進行時，未反應之5,6-二醯基抗壞血酸及鹼仍保留在 該含水層中。因此，當反應繼續進行時’產物係自發地溶解及分 離在該有機層中。在此過程中，反應速率藉由加入0.01至2重量 份之四級銨鹽類而變得更快速，以5,6-0-二醯基抗壞血酸計。四 級銨鹽類之例子係包括，但不限於，三甲基丁基銨氯化物 (trimethylbutylammonium chloride)等。 7The 201040152 COSM-02564TW sub-system reacts at the same rate, but using an excess of the ingredients, if desired, results in more efficient purification and higher yields. Such modifications are within the purview of those skilled in the art, and details are not described herein. Examples of the organic solvent used in the step a) include any aprotic solvent' and it is preferred to use an organic solvent such as acetone, diethyl ether, pentane, hexane, or heptane. Examples of sulfhydryl groups include, but are not limited to, acetyl chloride and benzoyl chloride. The reaction temperature in the protecting step is between room temperature and 50 ° C, preferably 30 to 50. (:, and the reaction time is from 0.5 Torr to 3 hours, preferably from 1 to 2 hours. The quantitative protection can be achieved at such temperatures and times. The protection is generally carried out at the same rate. However, 1 to 10% is used. The excess sulfhydryl halide can increase the yield and can be carried out by a person skilled in the art. Step b) is achieved by an interfacial reaction in a double layer of an aqueous layer and an organic layer. First, 5,6-di-branched ascorbic acid and a test (e.g., KHC03) are dissolved in the aqueous layer. Next, a calcined halide is added to the organic solvent layer (e.g., ethyl acetate and Q ethyl ether). The organic solvent was refluxed at a high temperature to produce 3-0-alkyl-5,6-0-dimercapto ascorbic acid. The reflux temperature can be appropriately selected depending on the solvent to be used. The obtained 3-0-alkyl-5,6-0-dimercapto ascorbic acid is dissolved in the organic layer, and when the reaction is continued, the unreacted 5,6-dimercapto ascorbic acid and the base are still Retained in the aquifer. Therefore, the product is spontaneously dissolved and separated in the organic layer as the reaction proceeds. In this process, the reaction rate becomes faster by adding 0.01 to 2 parts by weight of the quaternary ammonium salt, based on 5,6-0-dimercapto ascorbic acid. Examples of the quaternary ammonium salt include, but are not limited to, trimethylbutylammonium chloride and the like. 7
201040152 COSM-02564TW 步驟b)係持續！至2小時，接著藉由冷卻而終止。接著，實施 步驟c)去保B蔓所得之3_〇_院基_5,6_〇_二酿基抗壞血酸。該去保 護係於酸存在下，於—醇溶射實施。使用之酸類較佳為例如三 氣乙酸。醇類之例子包括，但不限於，異丙醇、丁醇、以及乙醇。 不受限制下，去保護-般係在50至70°CT實施2至8小時。 <有利效果> 藉由使用本發明之方法，可縮短整體反應時間。另外，由於當 q 3-〇_烷化反應繼續進行時，產物係溶解在有機層中，故促進產物 的刀離，因而可達到較高產率。因此，本發明具有可在室溫下短 時間内獲得所欲之南產率及純度之產物的優點，且可提供一種用 以大規模製造之具成本效益之方法。 <最佳態樣> 將以以下實施例詳細描述本發明。 實施例 實施例1 :保護步驟 〇 將1公斤抗壞血酸溶解在3.3公斤丙酮及0.29公斤己烷之混合 浴劑中，接著攪拌加入0.131公克之氯化乙醯至該溶液中。接著， 該反應係在4〇t：下實施2小時。在冷卻之後，在20。(：減壓下實施 蒸餾法以移除丙酮及己烷，以製造以乙醯基保護之5,6-二醯基抗 壞血酸。藉由紅外光光譜（IR)及氫核磁共振（b-NMR)確認產 物。 實施例：製備3-0-乙基-5,6-0-二乙醯基氧基抗壞血酸 將1公斤實施例1所製造之5,6-二乙醯基氧基抗壞血酸溶解在5 公斤一甲基酸胺及11公斤純水之混合水溶液中。接著，將〇 8201040152 COSM-02564TW Step b) is continuous! Up to 2 hours, then terminated by cooling. Next, step c) is carried out to protect the 3_〇_院基_5,6_〇_di-branched ascorbic acid obtained from B. The deprotection is carried out in the presence of an acid in an alcohol spray. The acid to be used is preferably, for example, triacetic acid. Examples of alcohols include, but are not limited to, isopropanol, butanol, and ethanol. Unrestricted, the general protection is carried out at 50 to 70 ° CT for 2 to 8 hours. <Advantageous Effects> By using the method of the present invention, the overall reaction time can be shortened. Further, since the product is dissolved in the organic layer when the q 3-〇_alkylation reaction is continued, the knife-off of the product is promoted, so that a higher yield can be attained. Accordingly, the present invention has the advantage of obtaining a product of desired yield and purity in a short period of time at room temperature, and provides a cost-effective method for large-scale manufacturing. <Best Aspect> The present invention will be described in detail by the following examples. EXAMPLES Example 1: Protection step 〇 1 kg of ascorbic acid was dissolved in a mixed bath of 3.3 kg of acetone and 0.29 kg of hexane, followed by stirring to add 0.131 g of chlorinated ethyl acetate to the solution. Next, the reaction was carried out for 2 hours at 4 Torr. After cooling, at 20. (: Distillation was carried out under reduced pressure to remove acetone and hexane to produce 5,6-dimercapto ascorbic acid protected with acetamidine. By infrared spectroscopy (IR) and hydrogen nuclear magnetic resonance (b-NMR) The product was confirmed. Example: Preparation of 3-0-ethyl-5,6-0-diethyldecyloxyascorbic acid 1 kg of 5,6-diethyldecyloxyascorbic acid produced in Example 1 was dissolved in 5 a mixed aqueous solution of kilograms of monomethylamine and 11 kg of pure water. Next, 〇 8
201040152 COSM-02564TW 公斤溴乙炫溶解在10公斤乙酸乙酯中。將兩溶液混合攪拌。在 60 C下反應2小時之後，會自水層中分離出一有機層，並使用過 量水沖洗該有機層三次。接著，在2〇t：下減壓蒸餾被分離出之該 有機層，得到標題化合物，產率97%。自第！圖確認產物之身分。 實施例3:製備3-0-乙基-抗壞血酸201040152 COSM-02564TW kg of bromide is dissolved in 10 kg of ethyl acetate. The two solutions were mixed and stirred. After reacting at 60 C for 2 hours, an organic layer was separated from the aqueous layer, and the organic layer was washed three times with excess water. Then, the organic layer was separated under reduced pressure to give the title compound (yield: 97%). Since the first! The figure confirms the identity of the product. Example 3: Preparation of 3-0-ethyl-ascorbic acid
將1公斤實施例2所製造之3_〇_乙基_5,6_二乙醯基氧基抗壞血 酸加入至含有10公克三就乙酸、〇.3公斤正丁醇、以及〇 5公斤水 之1公斤異丙醇溶液中，並在贼下授拌實施反應2小時。在室 溫下減㈣縮該溶液以製造—黏滞液體。加人乙醇至該黏滞液體 中亚/辰縮以得到3·乙基·抗壞血酸之粗結晶。接著，將3•乙基_抗 壞血酸之粗結晶自乙酸乙醋/乙醇（8:2)再結晶以得到8.6公克 (95%) 3-0-乙基-抗壞血酸之白色結晶。 mp.113至114。〇;氫核磁共振（1hnmr)(甲醇似類）口口以，谷 ，3·58 至 3 67 ( 2H，m)，3 77 至 385(ιη， m) ’ 4.54 (2Η，q) ’ 4.75 (1H，d，l 3Hz)。1 kg of 3_〇_ethyl_5,6-diethyldecyloxyascorbic acid produced in Example 2 was added to contain 10 g of triacetin, 33 kg of n-butanol, and 5 kg of water. In a 1 kg isopropyl alcohol solution, the reaction was carried out for 2 hours under a thief. The solution is reduced (4) at room temperature to produce a viscous liquid. Ethanol is added to the viscous liquid to reduce the crystals of 3·ethyl·ascorbic acid. Next, crude crystals of triethyl-ascorbic acid were recrystallized from ethyl acetate/ethanol (8:2) to give white crystals of 8.6 g (95%) of 3-0-ethyl-ascorbic acid. Mp.113 to 114. 〇; hydrogen nuclear magnetic resonance (1hnmr) (methanol-like) mouth, valley, 3.58 to 3 67 (2H, m), 3 77 to 385 (ιη, m) ' 4.54 (2Η, q) ' 4.75 ( 1H, d, l 3Hz).
【圖式簡單說明】 >第1圖所*騎_中所製備之3·〇·乙基_5紅乙醯基氧基抗 壞赢酸進行核磁共振光譜分析結果之_表。 【主要元件符號說明】 (無）[Simplified description of the drawing] > Figure 1 shows the results of nuclear magnetic resonance spectroscopy analysis of 3·〇·ethyl_5-erythroyloxy anti-bad acid prepared in the riding. [Main component symbol description] (none)
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103113333A (en) * | 2012-12-20 | 2013-05-22 | 浙江普洛康裕制药有限公司 | Synthesizing method of vitamin C ethyl ether |
| CN105218494A (en) * | 2015-11-16 | 2016-01-06 | 哈尔滨理工大学 | Vitamin C fat acid diester and preparation method thereof |
| CN110305085A (en) * | 2019-07-23 | 2019-10-08 | 宁夏启元药业有限公司 | Crystal form A, preparation method and the lightening compositions of 3-O- ethylascorbyl ether |
| CN110343096A (en) * | 2018-04-08 | 2019-10-18 | 湖北阿泰克生物科技股份有限公司 | A kind of method of round-robin method synthesis 3-O- alkyl -5,6-O- isopropylidene ascorbic acid |
| CN110642816A (en) * | 2019-09-25 | 2020-01-03 | 旖肽(上海)生物科技有限公司 | Crystalline 3-O-ethyl vitamin C and preparation method and application thereof |
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| CN112142697B (en) * | 2020-10-28 | 2022-05-06 | 浙江拓普药业股份有限公司 | Vc ethyl ether production process |
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| HRP930131A2 (en) * | 1993-02-05 | 1997-02-28 | Bozidar Suskovic | Amino-ascorbic acid derivatives, process for the preparation and use thereof |
| DE19750526A1 (en) | 1997-11-14 | 1999-05-20 | Basf Ag | Ascorbic acid derivatives containing cosmetic and pharmaceutical preparations |
| KR100500503B1 (en) * | 2001-05-30 | 2005-07-14 | (주)코스몰 | Process for preparing a crystal 3-0-alkyl ascorbic acid |
| KR100548989B1 (en) * | 2003-04-09 | 2006-02-08 | (주)코스몰 | Manufacturing of 3-O-Alkyl-ascorbic Acid |
| KR100761959B1 (en) * | 2006-10-12 | 2007-10-04 | (주)코스몰 | Method for preparating crystalline 3-o-alkyl-ascorbic acid |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103113333A (en) * | 2012-12-20 | 2013-05-22 | 浙江普洛康裕制药有限公司 | Synthesizing method of vitamin C ethyl ether |
| CN103113333B (en) * | 2012-12-20 | 2015-07-08 | 浙江普洛康裕制药有限公司 | Synthesizing method of vitamin C ethyl ether |
| CN105218494A (en) * | 2015-11-16 | 2016-01-06 | 哈尔滨理工大学 | Vitamin C fat acid diester and preparation method thereof |
| CN105218494B (en) * | 2015-11-16 | 2017-05-31 | 哈尔滨理工大学 | The preparation method of vitamin C fat acid diester |
| CN110343096A (en) * | 2018-04-08 | 2019-10-18 | 湖北阿泰克生物科技股份有限公司 | A kind of method of round-robin method synthesis 3-O- alkyl -5,6-O- isopropylidene ascorbic acid |
| CN110343096B (en) * | 2018-04-08 | 2022-12-02 | 湖北阿泰克生物科技股份有限公司 | Method for synthesizing 3-O-alkyl-5, 6-O-isopropylidene ascorbic acid by circulation method |
| CN110305085A (en) * | 2019-07-23 | 2019-10-08 | 宁夏启元药业有限公司 | Crystal form A, preparation method and the lightening compositions of 3-O- ethylascorbyl ether |
| CN110642816A (en) * | 2019-09-25 | 2020-01-03 | 旖肽(上海)生物科技有限公司 | Crystalline 3-O-ethyl vitamin C and preparation method and application thereof |
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