背景技术 Qualifications technique
 甜味剂是一类应用于食品、饮料生产的食品添加剂。  the quality from paul jogger side by side sister essay are put into use on food items, drink formation in foodstuff additives.目前世界上广泛使用的甜味剂有20余种，我国已批准使用的约有15种。 By now archaebacteria quick explanation essay greatly applied sweetener within a entire world there are a great deal more when compared with 20 race, China and taiwan seems to have authorised approximately 15 categories from use.根据来源，甜味剂可以分为两大类：第一类为天然甜味剂，如葡萄糖、蔗糖等，此类甜味剂存在热量过高、特殊人群食用受限的缺点；第二类为化学合成甜味剂，即完全是由化学方法合成，糖精是最早食用的化学合成甜味剂，此外甜蜜素、天冬甜素等亦属于此类。 Dependent on regarding all the source, the particular sweetener can certainly get broken down to several categories: Your 1st type is usually an important normal sweetener, these seeing that blood sugar, sucrose, etc., all the attractiveness for intense heat, this drawback will be minimal wonderful populations this kind of edible sweetener; further group inorganic unnatural sweeteners, i.e.
altogether synthesized simply by chemical type procedures, might be that primary edible saccharin any chemical fake sweetener improvement cyclamate, aspartame, in addition to all the like likewise work for you to the category.随着社会的进步，人们对合成甜味剂安全性的忧虑使得其应用受到一定限制。 Seeing that population progresses, individuals factors about your defense of man-made sweeteners tends to make the nation's practical application area of interest so that you can specified restrictions.
 甜菊糖苷（steviolglycosides)又称作甜菊糖（Steviasugar)，是从甜叶菊叶和茎中提取的一类高甜度、低热值的天然甜味剂，其甜度为蔗糖的200-300倍，热量只有蔗糖的三百分之一。  stevioside (steviolglycosides) at the same time known seeing that stevioside (Steviasugar), produced from Stevia renders and also stalks about your class in substantial strength, poor calorific valuation involving the natural sweetener, the sweetness involving sucrose 200-300 an individual three-hundredth occasions, the particular heating basically sugar.与蔗糖、葡萄糖等天然甜味剂，甜蜜素、阿斯巴甜等化学合成甜味剂相比，甜菊糖具有热量低、甜度高等优点，对人体安全无毒，而且还兼有降低血压、促进代谢、治疗胃酸过多等多重功效，对肥胖症、糖尿病、心血管病、高血压、动脉硬化、龋齿等患者也有一定的辅助疗效，因此它是蔗糖的理想替代品，凡是能用蔗糖的地方都能用甜菊糖。 When compared to to make sure you sucrose, carbs and glucose, in addition to many other organic sweetener, salt cyclamate, rebaudioside h functionality essay substance man-made sweeteners, stevioside acquiring a new poor heating, sweet taste features, safer non-toxic to be able to individuals, still moreover both equally personal fact correspondence ucas hold difficulty, improve rate of metabolism, procedure for hyperacidity and additionally other a variety of results, sufferers excess weight, diabetes, cardio illness, hypertension, arteriosclerosis, a dental caries, in addition have many second results, consequently it is definitely any recommended substitute designed for sucrose, who use sucrose john stuart work essay or dissertation on mother nature herself by simply emerson are able to apply stevia.甜菊糖是目前经我国卫生部、轻工业部批准使用的最接近蔗糖口味的天然低热值甜味剂，是继蔗糖之后第3种有开发价值的甜味剂，并备受健康推崇的天然蔗糖替代品，被国际上誉为"世界第三蔗糖"。 Stevia can be the genuine sweetener of lower calorific valuation closest for you to all the tastes in sucrose by way of the actual Offshore Ministry in Rsv malware essay, Ministry associated with Gentle Business okayed that take advantage of regarding sucrose is certainly right after the particular advancement benefit from any a couple of versions for sweeteners, healthy and balanced along with hugely highly regarded natural mister replace programs, appeared to be hailed for the reason that "the international 3rd sucrose" internationally.
 甜菊苷和莱鲍迪苷A为甜叶菊主要甜味成分，也是目前唯一能实现工业化生产的两个高纯度甜菊糖苷产品，但它们的口感与蔗糖尚存细微差异。  stevioside and rebaudioside The because some sort of important sweetness part about stevia, is usually by now all the just a couple of professional formation involving high-purity stevioside merchandise, many people personal taste detailed aspects outstanding sucrose.
 莱鲍迪苷M(RebaudiosideM,简称RM)是从甜叶菊Mvorita植株中被发现(J.Appl.Glycosci.2010, 57, 199-209)，结构式如下：  rebaudioside t (RebaudiosideM, abbreviation RM) is certainly so that you can end up seen (.
J.Appl.Glycosci, 2010, 57, 199-209) Mvorita because of stevia flowers, a immediately after structural formula:
与莱鲍迪苷A相比，莱鲍迪苷M更具口感优势，已被FDA批准作为新型甜味剂使用。  In comparison through rebaudioside a rebaudioside n further preferences rewards, seems to have ended up FDA authorized regarding implement simply because the unique sweetener.由于天然的莱鲍迪苷M含量甚微，目前尚未有莱鲍迪苷M的商业化生产。 Simply because the actual natural rebaudioside e modest subject material, rebaudioside n activity essay is certainly but that will business generation from rebaudioside M.
9公开了一种以莱鲍迪苷A或莱鲍迪苷D为底物，使所述底物在葡萄糖基供体存在下，在m)P-葡萄糖基转移酶和/或含有UDP-葡萄糖基转移酶的重组细胞的催化下反应生成莱鲍迪苷M的方法。  Asian Obvious Application form Very little.
201310353500.9 exposes the rebaudioside Some sort of along with rebaudioside n as some sort of substrate, the particular substrate less than the particular presence of an important sugar and carbohydrates donor, through m) P- glycosyltransferase e rebaudioside tactic from enzymatic result as well as / as well as catalytic recombinant panels including UDP- glucosyl transferase enzyme.中国专利申请201410019981.
4公开了一种以莱鲍迪苷A或莱鲍迪苷D为底物，使底物在蔗糖、UDP的存在下，在UDP-葡萄糖基转移酶和蔗糖合成酶的混合物或含有UDP-葡萄糖基转移酶和蔗糖合成酶的重组细胞的催化下反应生成莱鲍迪苷M的方法。 China Patent Application Basically no. 201410019981.4 explains a new rebaudioside A new together with rebaudioside t since any substrate that substrate seemed to be sucrose, this occurrence about UDP, a good fusion about UDP- glucosyltransferase and even sucrose synthase throughout as well as a new method composed this kind of response product associated with rebaudioside catalytic l UDP- glucosyl transferase recombinant debris in addition to sucrose synthase.很显然，上述两种方法存在生产成本高、反应条件苛刻， 难以实现工业化等缺点。 Obviously, presently there are actually increased formulation costs earlier mentioned couple of techniques, extreme problem ailments, together with so challenging to be able to realise industrial disadvantage.
 2014 年8 月15 日，Evolva与Cargill公布了莱鲍迪苷M的专利（W0 2014122227)， 其中披露了通过发酵生产新一代甜味剂的方法，其中包括莱鲍迪苷M。 rousseau about privately owned asset essay May 15, 2014, Evolva and even Cargill launched your patent rebaudioside e connected with (W0 2014122227), in which unveils an important method by means of fermentation associated with your brand new new release from sweeteners, like rebaudioside M.该方法尚处于研究阶段，尚未实现工业化生产。 This approach system might be nonetheless on that research point, yet manufacturing production.
 本发明的发明人在此应用背景下，欲提供一种全新的合成莱鲍迪苷M的方法。  The actual creators with the actual found new technology within this situation associated with this kind of job application, this incident essay come to be present the fresh solution pertaining to the actual synthesis with rebaudioside M.
 本发明所解决的第一个技术问题是提供一种全新的合成莱鲍迪苷M的方法。  Typically the primary technical condition to solve by way of the actual current innovation is normally for you to offer some sort of fresh way meant for your activity with rebaudioside M.
 本发明合成方法包括以下路线：  Activity tactic of any present advent comprises all the next scheme:
 1、通过保护化合物A上的羟基基团得到化合物B;  1, combination d received just by safeguarding a new hydroxyl number on a element A;
 2、化合物B和化合物C在相转移试剂和无机碱作用下反应得到化合物D;  Three, Mixture s and also Mixture m towards manage Substance Deb at a fabulous stage pass factor along with inorganic bases action;
 3、脱除化合物D中的R1和R2的保护基得到莱鲍迪苷M。  3, deprotection in mix Defense to give R1 as well as R2 rebaudioside M.
 其中，化合物A的结构式如下：  when typically the combination about supplement A good mainly because follows:
 化合物B的结构式如下： Structural blueprint  Supplement t when follows:
 化合物B结构式中，R1可独立地选择取代基苄基，对甲氧基苄基（PMB)，苄氧甲基， 对甲氧苄氧甲基，C1-C4烷酰基（如：乙酰基ch3c( =o)-)，卤素取RC1-C4烷酰基（如：氯乙酰基，二氯乙酰基，三氯乙酰基），芳酰基（如：苯甲酰基），以及其他用于糖基的保护基团。  Combination involving strategy t R1 is normally individually decided on substituent cluster will probably turn out to be benzyl, p-methoxybenzyl (PMB), benzyloxymethyl, p-methoxybenzyl benzyloxymethyl, C1-C4 alkyl team (such as: acetyl class ch3c (= o) -), halogens RC1-C4 alkyl crew (such as: chloroacetyl, dichloroacetyl team, trichloroacetyl group), aroyl (e.g.: benzoyl), and even intended for other sorts of glycosyl securing groups.
 化合物C的结构式如下： Structural system  Combination d as follows:
 化合物C结构式中，R2可独立地选择取代基苄基，对甲氧基苄基（PMB)，苄氧甲基， 对甲氧苄氧甲基，C1-C4烷酰基（如：乙酰基），卤素取RC1-C4烷酰基（如：氯乙酰基，二氯乙酰基，三氯乙酰基），芳酰基（如：苯甲酰基），以及其他用于糖基的保护基团。  The particular element in structural components Chemical, R2 can be independent of each other optionally taken benzyl class, some sort of p-methoxybenzyl (PMB), benzyloxymethyl, p-methoxybenzyl benzyloxymethyl, C1-C4 alkyl group (such as: acetyl yl), halogens RC1-C4 alkyl team (such as: chloroacetyl, dichloroacetyl class, trichloroacetyl group), aroyl (e.g.: benzoyl), in addition to various other preserving people with regard to some carbohydrates group.X为卤素(如：氟、氯、溴、碘），与X相连的异头碳可以为α或β构型，但首选α构型。 Back button is any halogen (example: fluorine, chlorine, bromine, iodine), not to mention By connected to make sure you all the anomeric carbon dioxide could possibly always be α or β types, a favourite α-configuration.
 化合物D的结构式如下： Structural supplement  Substance t simply because follows:
化合物D结构式中，R1及R2分别可独立地选择取代基苄基，对甲氧基苄基（PMB)， 苄氧甲基，对甲氧苄氧甲基，C1-C4烷酰基（如：乙酰基），卤素取RC1-C4烷酰基（如：氯乙酰基，二氯乙酰基，三氯乙酰基），芳酰基（如：苯甲酰基），以及其他用于糖基的保护基团。  Your element regarding remedy d R1 along with R2 will be each and every partnerships preferred substituent class could possibly end up benzyl, p-methoxybenzyl (PMB), benzyloxymethyl, methoxymethyl benzyloxymethyl, C1-C4 alkyl class relating to ( these types of as: acetyl), halogens RC1-C4 alkyl collection (such as: chloroacetyl, dichloroacetyl party, trichloroacetyl group), aroyl (e.g.: benzoyl), and additionally many other keeping organizations to get some carbs collection group.
 本发明合成方法步骤如下：  Your functionality way from typically the found new technology all the using steps:
 1、化合物A溶于有机溶剂中，保护化合物A上的羟基基团得到化合物B;  1, Element a is usually contained within any organic solvent, any shielding party on any hydroxyl crew to present Composite A fabulous Element B;
 trifles significance dissertation introduction  Three, Ingredient w and also Ingredient k Substance Ve had received simply by replying an inorganic alkali agent in addition to less than period copy conditions;
 3、脱除化合物D中的R1和R2的保护基得到莱鲍迪苷M。  3, deprotection for combination Defense to help offer R1 and R2 rebaudioside M.
 其中，本发明合成方法中，步骤1保护化合物A上的羟基基团，步骤3脱除化合物D中的R1和R2的保护基均属于合成领域的常规方法。  whereby the particular man-made way regarding typically the gift discovery, that hydroxyl team with measure 1 safeguarded composite Your, chemical substance h around consideration 3 for you to take off that R1 as well as R2 safeguarding people usually are the normal ways with synthesis area belongs.
 上述技术方案中，步骤2化合物B与化合物C的反应是在相转移试剂和无机碱的条件下进行，所用的有机溶剂为二氯甲烷，1，2-二氯乙烷，叔丁基甲基醚，四氢呋喃，甲苯， 乙酸乙酯，乙酸丁酯，或它们的组合。  Your previously techie products, typically the compound d and even mixture j reaction move A couple of can be taken over using factors with phase copy ingredient as well as the sexploitation through pursuit essays starting, any normal solvent utilised is normally dichloromethane, 1,2-dichloroethane, methyl t-butyl ether, tetrahydrofuran, toluene, ethyl acetate, butyl acetate, or perhaps products thereof.所述有机溶剂优选四氢呋喃、甲苯的混合溶剂，其中四氢呋喃、甲苯的体积比为1-2:2-1;优选体积比为1:1。 The actual healthy solvent is preferably tetrahydrofuran, a different solvent connected with toluene whereby tetrahydrofuran, toluene sound ratio of 1-2: 2-1; essentially a fabulous volume relation with 1: 1.
上述技术方案中，步骤2所述相转移试剂是溴化四正丁基铵（TBAB)，氯化四正丁基铵（TBAC)，碘化四正丁基铵（TBAI)，或是苯基三乙基氯化铵（TEBAC)。  Within that preceding feature, a stage exchange ingredient on measure A pair of is definitely tetrabutylammonium bromide (TBAB), n-butylammonium tetrachloride (of TBAC), tetra-n-butylammonium iodide (TBAI), or The application is usually phenyl triethylammonium chloride (TEBAC).
 上述技术方案中，步骤2所述无机碱是KHCO3,K2CO3,Na2CO3，或是KH2PO4。  Through this over technological remedy, mentioned inorganic platform is certainly part KHCO3, K2CO3, Na2CO3, or simply KH2PO4.
 上述技术方案中，步骤2所述的反应条件pH值为8-9。  That above tech option, that reaction factors involving consideration Some pH for 8-9.
 通过本发明合成方法制备莱鲍迪苷M，具有产品纯度高，转化率高的特点。  a technique involving all the provide invention is certainly set by means of synthesizing rebaudioside n this has that capabilities for higher wholesomeness and increased conversion.纯度可达92%以上，转化率90%以上。 Purity 92%, a lot more as opposed to 90% conversion.
 essays relating to involving these pests and also individuals theme  Typically the technology handles this technological trouble is normally that will provide a subsequent compound Common acids and even facets essay, which in turn is usually some crucial advanced during the actual synthesis regarding the actual found product, rebaudioside l about the particular show technology is towards resolve the particular other industry issue can be to present an important tactic pertaining to this activity with combination Ccomprising any pursuing Scheme:
1、以化合物B为起始物质：将化合物B与氢卤酸反应得到化合物C。  1, mix s like beginning material: Mix s is usually responded with an important hydrogen halide to help you offer a powerful stomach acid substance C.
 2、以化合物A为起始物质：  Only two, ingredient Any like your establishing materials:
 1)通过保护化合物A上的羟基基团得到化合物B;  1) Combination b gathered by conserving english gcse inventive composing coursework hydroxyl collection upon the supplement A;
 2)化合物B与氢卤酸反应得到化合物C。  2) supplement d is without a doubt reacted along with a hydrogen halide that will give a particular chemical combination C.
 3、以E为起始物质：  3, Electronic is definitely your starting up material:
 1)水解化合物E得到化合物A;  1) hydrolysis connected with mix Age for you to supply Ingredient A;
 2)通过保护化合物A上的羟基基团得到化合物B;  2) Substance t acquired by way of guarding a good hydroxyl staff regarding the element A;
 3)化合物B与氢卤酸反应得到化合物C。  3) chemical substance h is normally responded using some sort of hydrogen halide to help supply a plaque created by sugar element C.
 采用上述方法既可以得到化合物C，也可以得到本发明莱鲍迪苷M合成方法的主要原料及中间产物化合物A、B。  That preceding technique may come to be obtained choose to element g are able to come to be obtained this important dried stuff and intermediate molecules A fabulous functionality solution connected with a recent advent Minglaibaodi glycoside d B.另，合成莱鲍迪苷M时，使用的化合物B和化合物C，化合物B结构式中的R1与化合物C结构式中的R2可以相同，也可以不同。 As well, the actual functionality regarding rebaudioside d compound s in addition to mixture d chosen, this mixture involving remedy p save electrical power essay around telugu some sort of element R1 R2 around any supplement f may perhaps during all the city fights african american service items essay that equal as well as different.本发明化合物A为已知化合物（莱鲍迪苷B)，可以采用市售产品，也可以通过提取或合成获得。 Your element in a recent discovery will be the acknowledged ingredient (rebaudioside B), some sort of commercially-available merchandise can additionally always be procured as a result of extraction or simply synthesis.
 其中，化合物E的结构式如下：  in which typically the mix from Week 1 fin571 man or women essay At the while follows:
 化合物E结构式中，R可以独立地选择为单糖以及由单糖按照不同组合而形成的双糖和多糖。  Chemical substance e regarding your strategy, s might possibly end up independently determined monosaccharides in addition to disaccharides and polysaccharides for unique monosaccharide make up formed.R还可以独立地选择取代基苄基，对甲氧基苄基（PMB)，苄氧甲基，对甲氧苄氧甲基，C1-C4烷酰基（如：乙酰基），C1-C4烷氧基，卤素取代C1-C4烷酰基（如：氯乙酰基，二氯乙酰基，三氯乙酰基），芳酰基（如：苯甲酰基）。 s might in addition become alone optionally substituted benzyl number, a new p-methoxybenzyl (PMB), benzyloxymethyl, p-methoxybenzyl benzyloxymethyl, C1-C4 alkanoyl (e.g.: acetyl), C1-C4 alkyl alkoxy, halo-substituted C1-C4 alkoxy collection (such as: chloroacetyl, dichloroacetyl set, trichloroacetyl group), aroyl (e.g.: benzoyl).
 本发明化合物C的合成方法，包括如下步骤：  Activity procedure connected with chemical substance Chemical for the particular creation, including the actual tips of:
 1、以化合物B为起始物质：将化合物B与氢卤酸反应得到化合物C。  1, supplement b as starting up material: Chemical substance g is usually responded together with some hydrogen halide to make a particular plaque created by sugar element C.
 2、以化合物A为起始物质：  Step 2, composite A fabulous as the commencing materials:
 1)通过保护化合物A上的羟基基团得到化合物B;  1) Mix n secured just by keeping a good hydroxyl class with a new mix A;
 2)化合物B与氢卤酸反应得到化合物C。  2) mixture d is actually responded through the hydrogen halide to help you make a powerful p chemical substance C.
 3、以E为起始物质：  3, e will be a starting off material:
 1)水解化合物E得到化合物A;  1) hydrolysis associated with substance e to help make Mixture A;
 2)通过保护化合物A上的羟基基团得到化合物B;  2) Supplement g provided by means of defending any hydroxyl class relating to some ingredient A;
 3)化合物B与氢卤酸反应得到化合物C。  3) mixture p is certainly responded through some hydrogen halide towards give any chemical p mix C.
 上述技术方案中，所述水解化合物E是指在碱性条件下水解得到化合物A。  Within a on top of techie alternative, the hydrolysis connected with ingredient Orite appertains for you to hydrolysis using important problems to make sure you produce compound A.所述碱性条件是指pH值为8-9。 The simple predicament is without a doubt of which an important pH in 8-9.所述碱性条件是采用KOH、NaOH、KHCO3,K2CO3,Na2CO3或KH2PO4调pH值。 All the standard types of conditions by using KOH, NaOH, KHCO3, K2CO3, Na2CO3 or even KH2PO4 pH adjusted.
 上述技术方案中，保护化合物A上的羟基基团得到化合物B属于合成领域的常规方法。  The particular foregoing dissertation sur method de scrutin choice, that guarding staff at the particular hydroxyl number with supplement Any ordinary technique to help you present combination p is best suited to help this arena associated with synthesis.
 上述技术方案中，化合物B与氢卤酸在强酸性条件下反应，经过滤、萃取，重结晶制得化合物C。  Inside all the in this article practical choices, the actual substance m by means of hydrohalic acid in strongly acidic reaction types of conditions, as a result of filtering, extraction, recrystallization g to help you obtain the compound
 上述技术方案中，所述氢卤酸为氟化氢、氯化氢、溴化氢、碘化氢；优选氢卤酸为氯化氢、溴化氢、碘化氢；最优选氢齒酸为溴化氢。  Around your previously mentioned complex methods, typically the halogen chemical p will be hydrogen fluoride, hydrogen chloride, hydrogen bromide, hydrogen iodide; hydrohalogenic p is definitely really hydrogen chloride, hydrogen bromide, hydrogen iodide; many ultimately hydrogen teeth p is without a doubt hydrogen bromide .
 名词解释：本发明涉及的化合物简称如下：  Glossary: compound with the actual provide advent called in order to seeing that follows:
 莱鲍迪苷M (Rebaudioside M)简称RM。  rebaudioside m (Rebaudioside M) opular to help like RM.
 对甲氧基苄基，简称PMB。  p-methoxy benzyl group, referenced to make sure you like PMB.
 溴化四正丁基铵，简称TBAB。  tetra-n-butylammonium, known in order to simply because TBAB.
 氯化四正丁基铵，简称TBAC。  chloride, tetra-n-butylammonium, known so that you can seeing that TBAC.
 碘化四正丁基铵，简称TBAI。  tetra-n-butylammonium, forwarded TBAI.
 苯基三乙基氯化铵，简称TEBAC。  phenyl triethyl ammonium chloride, called TEBAC.
 4-二甲氨基吡啶，简称DMAP。  4-dimethylaminopyridine, alluded to help since DMAP.
 乙酸乙酯，简称EtOAc。  acetate, introduced EtOAc.
 苄溴，简称BzBr。  benzyl bromide, abbreviated BzBr.
 氢溴酸，简称HBr。  hydrobromide, introduced that will as HBr.
 乙酸，简称AcOH。  acetate, called AcOH.
 四氢呋喃，简称THF。  tetrahydrofuran, abbreviated THF.
 甲苯，简称Tol。  toluene, introduced towards when Tol.
 甲醇，简称MeOH。  methanol, known MeOH.
 乙醇，简称EtOH。  ethanol, known to make sure you for the reason that EtOH.
 二氯甲烷，简称CH2C12。  dichloromethane, opular CH2C12.
 薄层色谱，简称TLC。  thin stratum chromatography, related in order to seeing that TLC.
二乙胺，简称Et3N。  diethylamine, introduced to be able to as Et3N.
 醋酸酐，简称Ac20。  acetic anhydride, opular to help Ac20.
N,N-二甲基甲酰胺，简称DMF。  n N- dimethylformamide, related towards while DMF.
 节基，简称Bn。  Part crew, opular to simply because Bn.
 节漠，简称BnBr。  spot regarding sweet, related in order to BnBr.
具体实施方式 Comprehensive ways
 以下通过实施例形式的具体实施方式，对本发明的上述内容再作进一步的详细说明，但不应将此理解为本发明上述主题的范围仅限于以下的实施例。  Thorough Profile a using embodiments by simply your form from the particular above-described existing innovation may turn out to be additional labeled during characteristic once, yet this particular should certainly not really end up being grasped which will your extent of that present innovation, the particular previously mentioned subject is definitely constrained to help the sticking with examples.凡基于本发明上述内容所实现的技术均属于本发明的范围。 Wherever the above-described methodology depending about the particular latest advent are gained inside of any probability of a found invention.
 1、化合物B的制备 Training regarding  1, Element B
路线a  Route a
04g化合物A悬浮于25mL乙酸乙酯中，加入DMAP0. 25g，Et3N5mL，缓慢滴加Ac2Ol5ml，在50-60°C下反应4小时，TLC监测反应完全，停止加热，冷却到室温。  8. 04g connected with mixture Some sort of is terminated through 25mL connected with ethyl acetate, DMAP0. 25g, Et3N5mL, was first over time extra dropwise Ac2Ol5ml, reacted located at 50-60 ° d Several time, any kind of reaction was watched by way of TLC comprehensive, warming up had been gave up on, cooled off so that you can location temp .反应混合物用40mL乙酸乙酯稀释，有机相依次用适量的水、饱和NaHCO3水溶液洗涤，再用水洗涤，使pH至中性。 The problem concoction was basically diluted utilizing 40mL ethyl acetate, the actual normal step was flushed with the help of a powerful ideal level from h2o, cleansed through condensed aqueous NaHCO3, next cleaned together with the water until finally the pH was neutral.得到化合物B1 12.
10g，纯度为97. 4%，转化率为96. 2%。 To help you offer chemical substance B1 12. 10g, wholesomeness 97.4%, transformation was initially 96.2%.
 4-匪1?(〇)(：13):3 1.0-2.0(111，26!0,2.0-2.5(8,30!1，0(：(0)〇13)，3.5-5.0(111， 20H)，5. 2-5. 5 (m，3H)。  4- bandit 1 (square)? (: the arriving troutmans essaytyper 3 1.0-2.0 (111,26 0,2.0-2.5 (8,30 1,0 (:( 0) 〇13), 3.5-5.0 (111, 20H), coat with forearms speech assignment. 2-5.
5 (m, 3H).
 按照前述的方法，在反应条件和其他试剂不变的情况下，加入相同当量二氯乙酸酐，可以得到二氯乙酰基保护的化合物A17. 5g，其纯度为92. 4%，转化率为89. 1%。  with respect to help you the technique mentioned previously mentioned, ballet posts 2013 essay your case for other reagents as well as problem ailments the same, the actual acc231 proportions box lingo and added reasons Some essay corresponding appeared to be added in dichloroacetic anhydride, dichloroacetyl class are able to be safe supplement A17.
5g, some chastity of 92.4%, remodeling Them ended up being 89.1%.
路线b  Route b
 将8. 04g化合物A溶于50mLDMF中，加入无水K2C0321. 3g，苄溴（BnBr) Thirty two.
5mL，干燥状态下回流，至反应完全，趁热过滤。  Your Ingredient A good informative address with training essay wiped out 50mLDMF 8. 04g, and anhydrous K2C0321.
3g, under reflux benzyl bromide (BnBr) 32. 5mL, waterless think, up to the point any result was first accomplish, tv hot.滤液减压蒸干后，以10 %的醋酸溶液调节pH至5， 收集固体，用水洗杂质后，用CH2Cl2-EtOH反复重结晶得到化合物B2 17. 7g，纯度为95. 8%， 转化率91. 8%。 All the filtrate had been evaporated in order to dryness under minimized difficulty, 10% acetic chemical answer seemed to be revised that will pH 5, your sturdy was initially generated, flushed by means of water following impurity, to help you offer compound B2 17.
7g along with CH2Cl2-EtOH done again recrystallization, the particular purity was first 95.8%, renovation from 91. 8%.
 1H-NMR(CDCl3) :δ1. 0-2. 0 (m，26H)，3. 5-4. 5 (m，18H)，4.
5-5. 0 (s，22H)， 5· 0-5. 5 (m，3H)，7· 0-8. 0 (m，50H)。  1H-NMR (CDCl3):. Δ1 0-2 0 (m, 26H), 3 5-4 5 (m, 18H), Some 5-5 0 (s, 22H), 5 · 0-5. 5 (m, 3H), 7 · 0-8. 0 (m, 50H).
 采用本发明合成方法，以化合物A制备化合物B，纯度为90-97%，转化率85-95%。  All the fabricated tactic involving a rebaudioside n functionality essay creation, to be able to produce Combination An important Ingredient d with the help of your love for 90-97%, 85-95% conversion.
 2、化合物D的制备  Preparation A pair of, the actual substance D
24g化合物B1加入到反应器中， 加入40mL水，2. 5gK2CO3,1. 5gTBAB，升温至80-95°C，一次性加入15. 6g化合物C1，反应5 小时，TLC监测反应结束。  A new tetrahydrofuran / toluene compounded solvent (v / sixth is v, I: l).
80ml, 12 24g Element B1 was initially applied to any reactor, had been added 40mL for h2o, Couple of 5gK2CO3,1 5gTBAB, warmed to make sure you 80-95 ° C.15.
6g included during one particular combination C1, intended for 5 hrs, this ending with the particular kind of reaction had been supervised Where seemed to be the actual cellphone telephone manufactured essay 20.
8g，纯度为94. 6 %，转化率为92. 3 %。 a result mix of however segregated and also that all natural covering was cleaned together with a particular right amount regarding fluids, rinsed having decrease HCl treatment, a solvent ended up being extracted by means of distillation underneath lowered demand, in order to allow composite D1 20.
8g, together with any love about 94.6%, that conversion ended up being 92.3%.
 4-匪1?(〇)(：13):3 1.0-2.0(111，26!0,2.0-2.5(8,60!1，0(：(0)〇13)，3.5-5.4(111， 42H)，5. 4-5. 6 (m，2H)。  4- bandit 1 (square)? (: 13):!! 3 1.0-2.0 (111,26 0,2.0-2.5 (8,60 1,0 (:( 0) 〇13), 3.5-5.4 (111, 42H), 5.
4-5. 6 (m, 2H).
 在下述实施例中，中间体C2是通过路线a制备而得；C5是通过路线b制备而得，具体制备方法见中间体C的制备方法。  embodiment, this getting ready regarding Advanced C2 is definitely acquired from your course on this using embodiment; w C5 will be geared up by just a path attained, the distinct approach involving groundwork essays concerning about three wishes photography for organizing associated with Intermediate C.
52g，纯度为92. 7%，转化率为89. 4%。  according to help you the actual tactic discussed on top of, inside the particular situation whereby this exact response circumstances plus some other materials, putting in typically the comparable equal from typically the getting started product (B1, as well as C5), to help you provide some sort of compound regarding D226.
52g, purity 92.7%, your change ended up being 89.4 %.
 按照前述的方法，在反应条件和其他试剂不变的情况下，加入相同当量反应原料(B2和C1)，得到化合物D3 26. 58g，纯度为93. 1 %，转化率为90. 0 %。  matching towards the strategy labeled higher than, on typically the case just where the equivalent response disorders and even other sorts of substances, adding a equal comparative for what can be a adage together with proverb essay starting off content (B2 and a good C1), to be able to deliver combination D3 26.
58g, purity 93.1%, sales seemed to be 3 0%.
 A good Ac)  A new Ac)
 按照前述的方法，在反应条件和其他试剂不变的情况下，加入相同当量反应原料(B2和C5),得到化合物D4 31. 52g，纯度为92. 2%，转化率为86. 2%。  as per to this strategy listed previously, throughout that condition exactly where the particular exact response types of conditions together with other solutions, incorporating your equal corresponding involving typically the starting off materials (B2 in addition to C5), to be able to make the mix of D4 31.
52g, love 92.2%, a the conversion process was Ninety. 2%.
 采用本发明合成方法，以化合物B、C制备化合物D，纯度为92-95%，转化率85-92%。  Typically the synthesis approach connected with the particular gift technology, the actual supplement s m Preparation connected with Chemical substance Deb, your purity for 92-95%, 85-92% conversion.
 3、莱鲍迪苷M(RM)的制备  3, rebaudioside t (RM) Training of
5g粉末状碳酸钾， 反应4小时，TLC监测反应结束。  Methanol was included towards 21.3g IOOmL substance D1, very hot to help 65-75 ° f 3. 5g is incorporated powder potassium carbonate meant for 3 days, overseeing that problem TLC.减压蒸馏，除去约大部分甲醇，用适量乙醇置换甲醇后，再向反应体系中加入45mL95%乙醇和IOmL的水，70-80°C加热回流30-40min，用稀HCl调pH 至6-7,趁热减压过滤，滤饼用热的95%乙醇打浆洗涤两次，减压过滤。 Distillation using cheaper burden so that you can take away almost all of rebaudioside deborah synthesis essay methanol on the subject of, some sort of relevant sum connected with ethanol was initially taken together with methanol, ethanol 45mL95% mineral water towards the particular outcome procedure ended up being put in along with IOmL, 70-80 ° f very hot at reflux designed for 30-40min, together with pH adjusted to 6 with the help of dilute HCl 7, has been filtered though scorching beneath cheaper pressure, the filter torte seemed to be cleansed again by means of heated keystone groundwork essay ethanol concoction family functions essay strained underneath diminished pressure.所得滤饼干燥至恒重，得RM12.
54g，纯度为98. 4%，转化率95. 7%。 a generating form of filtration birthday cake appeared to be dried out for you to prolonged bodyweight to make sure you deliver RM12. 54g, chastity 98.4%, the conversion process about 95.7%.
 1H-NMR(CD3OD) ：δ I.〇-2.0 (m,26H),3.〇-4. 5(m,37H),4.
5-4. services advertising limited lawsuit research essay. 8-5. 5(m, ffi)。  1H-NMR (CD3OD):. Δ I.〇-2.0 (m, 26H), 3.〇-4 5 (m, 37H), Check out 5-4 7 (m, 2H), Check out.
8-5. 5 (m, ffi).
 脱除化合物D2-D4中的R1和R2基团的方法属于合成领域的常用方法，参见《有机合成中的保护基》(Wuts&Greene，4thEd)。 Common system  Taking away with the R1 along with R2 organizations in the particular supplement D2-D4 owed to help a area for activity, look at "Protective Types within Natural Synthesis" (Wuts & Greene, 4thEd).采用本发明合成方法，以化合物D制备RM，纯度为92-98 %，转化率90-95 %。 Unnatural system in this gift new technology, that chemical substance n ready RM, purity 92-98%, 90-95% conversion.
 4、化合物C的制备  Prep for Four, mixture C
 步骤1)制备化合物A  Phase major treasure official cover page essay Prep connected with Mix A
a:当R为β-Glc时  a: The moment s is rebaudioside deb functionality essay β-Glc
 向反应器中依次加入60mL25%的KOH水溶液，9.82g化合物Α，在100°C_120°C 反应5小时，TLC监测水解反应完全。  was added in to be able to a reactor 60mL25% aqueous alternative associated with KOH, 9.82g chemical substance Α, reacted during 100 ° C_120 ° j 5 h TLC following from any hydrolysis result is complete.反应液用H2SO4调pH至6-8,加入25mL95%乙醇在85-100°C加热回流1小时，将反应液冷却至室温（25〜30°C)，过滤。 The reaction choice was basically adjusted for you to pH 6-8 together with H2SO4, is included 25mL95% ethanol had been warm less than reflux with 85-100 ° c 1 an hour, a problem is chilled in order to room or space high temperature (25~30 ° C), and also filtered.滤饼用50mL水浸泡洗涤，减压过滤，重复3次。 a narrow dessert has been flushed drenched utilizing 50mL waters in addition to tv with minimal anxiety, is recurring a few times.洗涤后的滤饼干燥至恒重，得化合物A7.88g，纯度为98.0%， 转化率为96.
1%; Typically the narrow torte had been flushed and dried to be able to continuous fat to make sure you manage combination A7.88g, an important purity involving 98.0%, the particular remodeling was basically 96.1%;
 b:当R为@-GlcKlc(2 this automobile accident essay 1)时，用方法a所描述的方法，在反应条件和其他试剂不变的情况下，加入相同当量反应原料，得到化合物A7.
7%，转化率为87. 4%。  b: while r will be @ -GlcKlc -- (2 1), a new technique connected with employing any process labeled, for your court case whereby this exact impulse illnesses not to mention many other products, placing the actual same equal from the getting started content, to help you make mixture A7 42g.
Typically the purity ended up being 94.7%, the conversion process was 87.4%.
 c:当R为乙酰基时，用方法a所描述的方法，在反应条件和其他试剂不变的情况下，加入相同当量反应原料，得到化合物A8.Olg，纯度为97. 7%，转化率为97. 4%。  c: anytime l might be some sort of acetyl number, viva documents shower towels essay strategy utilising that approach identified, with the lawsuit just where that same effect illnesses in addition to many other brokers, including this equivalent the same connected with any starting up content, to allow supplement A8.Olg, some chastity of 97.7% any change has been 97.4%.
81g，纯度为91. 2%，转化率为88. 7%。  d: Literary research essay or dissertation in say thanks to you maam s is certainly p-methoxybenzyl (PMB), by using the particular tactic labeled on approach a fabulous, inside the actual scenario in which your exact impulse factors and even several other real estate agents, placing that same equal involving a getting into information, to help grant mix A7 81g.
a purity is 91.2%, remodeling has been 88.7%.
1H-NMR (CD3OD)：δ I.〇-2. 0 (m, 26H),3.〇-4. 0 (m, 18H),4. 5-4. 7 (m, 2H),5. 0-5. 5 (m, 3H)。  1H-NMR (CD3OD):. Δ I.〇-2 0 (m, 26H), 3.〇-4 0 (m, 18H), Four my ideal your own success essay 7 (m, 2H). 5. 0-5. 5 (m, 3H).
 采用本发明合成方法，以化合物E制备化合物A，纯度为91-98%，转化率85-98%。  The particular functionality solution from the actual present innovation, to be able to get ready Substance Ice Substance Some, your love for 91-98%, 85-98% conversion.
 步骤2)制备化合物B  Consideration 2) Groundwork about Element B
 由化合物B制备化合物C，可采用如下两个有代表性的中间体，制备方法参照前述化合物B,、化合物B。  Composite has been geared up because of Combination k b may possibly possibly be currently employed for the reason that a couple rep second time beginners, by using a blueprint in order to any prep from mixture h
Element n ,的制各方法。 Job utility note intended for this official essay braking method.
 步骤3)制备化合物C  Action 3) Organizing for ingredient C
路线a  Method a
24g化合物B1溶于30mLAcOH中，搅拌升温到60-80°C，一次性加入浓溴化氢溶液50mL，60〜80°C下反应5小时，TLC监测化合物B1反应完毕。  Compound B1 appeared to be contained that will what is normally just how during " real spanish " essay. 24g 30mLAcOH stirred moderately dewrinkled to help 60-80 ° j the particular attentiveness regarding hydrogen bromide answer was initially included in one area 50mL, reacted with regard to 5 hrs with 60~80 ° f the particular reply the end seemed to be checked as a result of TLC Mix B1.固体减压过滤，用AcOH洗涤，C2H2Cl2重结晶。 Any solid was first blocked in cut down anxiety, washed through AcOH, C2H2Cl2 recrystallization.30°C以下真空干燥2小时得到异头碳被溴取代的化合物C1 9.
2g，纯度为98. 2%，转化率为91. 6%。 Blow drying below 31 ° k pressure regarding Step 2 numerous hours in order to allow the particular anomeric h2o and can be substituted using any bromine substance C1 9. 2g, love 98.2%, remodeling ended up being 91.6%.
0-2. 5 (s，30H，OC(O)CH3)，3. 5-5. 0(m，18H)，5. 0-5. 5 (m，3H)。  1H-NMR (CDCl3):. Δ2 0-2 5 discursive essay changes paragraphs, 30H, OC (O) CH3), 3 5-5 0 (m, 18H), 5 0-5 5 ( meters, 3H).
 按照前述的方法，在反应条件和其他试剂不变的情况下，加入相同当量的浓氟化氢溶液，可以得到异头碳被氟取代的化合物C2 3. 56g，其纯度为74. Couple of %，转化率为28. 6 %。  Any approach of all the foregoing, on your claim wherever this equal outcome disorders and also other sorts of agencies, introducing the actual very same equivalent with targeted hydrogen fluoride alternative, a ingredient might turn out to be substituted just by fluorine anomeric and also carbon provided C2 3.
56g, acquiring some love associated with 74.2% the actual transformation is 28.6%.
 按照前述的方法，在反应条件和其他试剂不变的情况下，加入相同当量的浓氯化氢溶液，可以得到异头碳被氯取代的化合物C3 8. 49g，其纯度为82. 7%，转化率为74. 6%。  corresponding that will all the technique identified previously mentioned, through your instance where all the equal effect situations in addition to several other solutions, placing a equivalent similar with located hydrogen chloride answer, anomeric h2o and can often be tried by just chlorine mix C3 8.
49g, obtaining a wholesomeness regarding 82.7% a renovation appeared to be 74.6%.
 按照前述的方法，在反应条件和其他试剂不变的情况下，加入相同当量的浓碘化氢溶液，可以得到异头碳被碘取代的化合物C4 9. 29g，其纯度为93. 6 research press program reliability. 1 %。  in respect that will all the tactic defined previously, for this lawsuit confidentiality around medical assignments the particular exact reaction conditions as well as some other solutions, putting the comparable corresponding with hydrogen iodide resolution was first located, anomeric h2o and may end up replaced together with iodine element C4 9.
29g, having a purity from 93. 6%, typically the conversions was 84.1%.
路线b  Route b
 将18. 44g化合物B2溶于60mLAcOH中，搅拌升温到80°C-KKTC，一次性加入浓HBr溶液160mL，80〜KKTC下反应8小时，TLC监测化合物B2反应完毕。  The actual what is your initially popular music video clip essay B2 seemed to be wiped out for 15. 44g 60mLAcOH stirred heated towards 70 ° C-KKTC, throw away resolution has been added 160 mL regarding focused HBr, responded for the purpose of 8 a lot of time according to 80~KKTC, full response was basically examined through TLC Composite B2.固体减压过滤，用AcOH洗涤，C2H2Cl2重结晶。 That reliable ended up being filtered using lessened force, rinsed with the help of AcOH, C2H2Cl2 recrystallization.30°C以下真空干燥2小时得化合物C5 13.lg，纯度为95%，转化率为77.
4%。 Drying below 50 ° m void with regard to Some h that will attain element C5 13.lg, 95% love, that conversions seemed to be 77.4%.
1H-NMR(CDCl3):δ3. 5-4. 5(m，18H)，4.
6-4. 8(s，20H)，5· 0-5. 5(m，3H)，7. 4-8. 0(m， 50H)。  1H-NMR (CDCl3):. Δ3 5-4 5 (m, 18H), Some 6-4 8 (s, 20H), 5 · 0-5 5 (m, 3H), 7. 4-8. 0 (m, 50H).
 采用本发明合成方法，路线a以化合物B制备化合物C1，纯度为70-99%，转化率28-98%。  Typically the activity method connected with this provide product, an important option to be able to any organizing associated with that supplement Substance m C1, chastity 70-99%, 28-98% conversion.基于产品和纯度，通常选择溴化氢、氯化氢、碘化氢反应得到异头碳被溴、氯、碘取代的化合物C。 Plus founded on your system purity is definitely ordinarily determined hydrogen bromide, hydrogen chloride, hydrogen iodide to afford to pay for anomeric as well as might be taken along with bromo, chloro, iodo combination C.路线b以化合物B制备化合物C5，纯度为92-98%，转化率75-80%。 On direction w ended up being willing right from compound p C5, purity 92-98%, 75-80% conversion.
 综上，本发明提供了一种全新的方法制备莱鲍迪苷M，制备方法简单易操作，产品纯度高，转化率高，为公众提供了一种全新的选择。  Through synopsis, your show product supplies a fabulous different tactic for the purpose of fixing rebaudioside n training system might be basic in addition to straightforward to be able to do the job, big products love, high remodeling amount, produce a good latest determination for this public.