DOCSLIB.ORG

Enantioselective Alcohol Synthesis Using Ketoreductases, Lipases Or an Aldolase

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Enantioselective Alcohol Synthesis Using Ketoreductases, Lipases Or an Aldolase Enantioselective Alcohol Synthesis using Ketoreductases, Lipases or an Aldolase Menno J. Sorgedrager Cover: Representing “Diversity in Parameter Space” Part of a screenprint by J.C. van de Griendt; in honour of my father Enantioselective Alcohol Synthesis using Ketoreductases, Lipases or an Aldolase Proefschrift ter verkrijging van de graad van doctor aan de Technische Universiteit Delft, op gezag van Rector Magnificus, prof. dr. ir. J.T. Fokkema, voorzitter van het College van Promoties, in het openbaar te verdedigen op 29 mei 2006 om 12.30 uur door Menno Jort SORGEDRAGER ingenieur in de bioprocestechnologie geboren te Groningen Dit proefschrift is goedgekeurd door de promotor: Prof. dr. R.A. Sheldon Toegevoegd promotor: Dr. ir. F. van Rantwijk Samenstelling promotiecommissie: Rector Magnificus Voorzitter Prof. dr. R.A. Sheldon Technische Universiteit Delft, promotor Dr. ir. F. van Rantwijk Technische Universiteit Delft, toegevoegd promotor Prof. dr. W.R. Hagen Technische Universiteit Delft Prof. dr. J.A.M. de Bont Technische Universiteit Delft Prof. dr. A. Liese Technische Universiteit Hamburg Prof. dr. ir. A.P.G. Kieboom Universiteit van Leiden Dr. G. Huisman Codexis Inc. (USA, CA) The research described in this thesis was financially supported and performed in cooperation with Codexis inc. (Redwood City, USA). ISBN: 90-9020702-3 Copyright 2005 by M.J. Sorgedrager All rights reserved. No part of the material protected by this copyright notice may be reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, or by any information storage and retrieval system, without written approval from the author. Contents INTRODUCTION Chapter 1 Introduction 1 PART I: LIPASE CATALYSED RESOLUTION OF ALDOL ADDUCTS Chapter 2 Lipase catalysed Resolution of Nitro aldol Adducts 21 Chapter 3 Optimising the Deracemisation of Nitro aldol Adducts 33 PART II ENANTIOSELECTIVE CARBONYL REDUCTION Chapter 4 Asymmetric Reduction with Candida Magnoliae Ketoreductase S1 47 Chapter 5 Asymmetric Carbonyl-Reductions with Microbial Ketoreductases 63 PART III ENANTIOSELECTIVE ALDOL REACTION: DERA Chapter 6 Production and Optimisation of 2-deoxyribose-5-phosphate Aldolase 79 Chapter 7 DERA as Catalyst for Statin Precursors 97 Chapter 8 Cross-linked Enzyme Aggregates of DERA 113 Summary 125 Samenvatting 127 Dankwoord 129 Curriculum vitae 132 1 Introduction Introduction Introduction The carbonyl group is probably the most important functional group in organic chemistry. Besides aldehydes and ketones, many functional groups contain the C=O bond, to which they own much of their behaviour in chemistry, such as carboxylic acids, acidhalides, acid anhydrides, esters and amides. When the molecule is bearing at least one α-hydrogen, which is acidic due to the electron-withdrawing effect of the carbonyl group and therefore can be abstracted by a strong base, these compounds are able to react via the resulting enolate ion. This forms the basis for a variety of synthetically usefull C-C bond forming reactions. Michael addition, aldol and Claissen reactions are examples of this reaction pathway. One of the most important of these reactions is probably the aldol reaction. Besides taking a central role in synthetic organic chemistry, this reaction is vital for all living organisms in nature. Aldol-type reactions are the key step in the metabolic pathways of micro-organisms, where it takes part in the breakdown of carbohydrates. Besides its role in anabolism, the aldol reaction is often applied in catabolism as well. The aldol reaction is initiated by the formation of the enolate by a base, followed by nucleophilic attack hereof on another carbonyl carbon (Figure 1.1). Depending on the reaction conditions it is possible to isolate the β-Hydroxy carbonyl compound or the unsaturated product that is formed by subsequent dehydration. In the latter case it is referred to as aldol condensation. β-Hydroxy carbonyl compounds are versatile and interesting intermediates. They can easily be synthesised directly via an aldol reaction of the corresponding aldehydes. The β-ketoesters, later described in this Chapter in connection with their reduction into β-Hydroxy esters, are easily accessible via the aldol reaction analogue for esters known as the Claisen condensation. Base H H O OH dehyration O - - O H2C O H2C O O Figure 1.1 The aldol reaction and subsequent condensation of acetaldehyde 2 Chapter 1 The demand for optically pure intermediates has grown rapidly in recent years. Therefore it is of growing importance to control chirality during a reaction. Although there are various chemical methods available1 biocatalysts are more and more applied to achieve this goal.1,2 Enzymes from the classes hydrolases, oxidoreductases and lyases are synthetically interesting for this purpose. Lipases, able to hydrolyze esterbonds; Ketoreductases, able to reduce carbonyl groups and aldolases that perform aldol reactions are well suited to synthesize enantiopure secondary alcohols. Biocatalysis: Kinetic resolution vs asymmetric synthesis Two strategies are possible to obtain homochiral compounds. One is a kinetic resolution of a racemic mixture, in which the enzyme catalyses the reaction of the two enantiomers of the substrate with different rates. The lipase mediated esterification of racemic secondary alcohols (Chapters 2 and 3) is a well known example of applying a kinetic resolution strategy. The other is an asymmetric synthesis starting from a prochiral substrate. In an asymmetric synthesis a new chiral centre is introduced into the substrate molecule. Examples of asymmetric syntheses, which are reported in this thesis, are the asymmetric reduction mediated by ketoreductases (Chapters 4 and 5) and the DERA catalysed aldol reaction (Chapters 6-8). The efficiency of a resolution process is dependent on the difference in rate in which the two enantiomers are converted. This is indicated with the enantiomeric ratio (E), which is the ratio of the two pseudo-first order kinetic rate constants (eq. 1.1). The enantiomeric excess of a compound (ee) is the excess amount of one enantiomer compared to the total amount of both enantiomers (eq. 1.2). The enantiomeric ratio: R RR k ()VKmax / m E ≡= (eq. 1.1) S SS k ()VKmax / m 3 Introduction The enantiomeric excess: ()cc− ee = RS (eq. 1.2) ()ccRS+ cx: Concentration enantiomer x The E value can be determined from experimental data via the conversion and either the ee of the substrate or the ee of the product.3 ln{() 1−−ξ ( 1 ees )} Via substrate: E = (eq. 1.3) ln{}()() 1−+ξ 1 ees ln{ 1−+ξ ( 1 eep )} Via product: E = (eq. 1.4) ln{} 1−−ξ () 1 eep E: Enantiomeric ratio ees: Enantiomeric excess of the substrate eep: Enantiomeric excess of the product ξ: Conversion An alternative method for calculating the enantiomeric ratio (E) directly from the enantiomeric excess of the substrate (ees) and the product (eep) is given by equation 1.5. The conversion of an irreversible reaction without substrate inhibition (up to 40% conversion) can then be calculated directly from the optical purities of the substrate (ees) and the product (eep) according to equation 1.6.3 ()11−+ee() ee Direct from ee’s: E = lnss ln (eq. 1.5) 11++ee ee ee ee ()sp() sp ee Conversion: ξ = s (eq. 1.6) ()ees + eep In a classical kinetic resolution two enantiomers of a racemic mixture are transformed to product with different reaction rates. In the ideal situation only one of the enantiomers reacts to product and thus yields a maximum conversion of 50 % of the total amount of substrate. To overcome this limitation many efforts have been made to combine the racemisation of the substrate in the resolution proces4 in a so-called dynamic kinetic resolution 4 Chapter 1 (DKR, Figure 1.2) The biggest challenge here is to find conditions that are compatible with both processes. Fast Fast (S)-Substrate (S)-Product (S)-Substrate (S)-Product in Situ Racemisation Slow Slow (R)-Substrate (R)-Product (R)-Substrate (R)-Product Classical kinetic resolution Dynamic kinetic resolution Figure 1.2 General schemes for a classical kinetic resolution and a dynamic kinetic resolution Lipase resolution Lipases are enzymes of the hydrolase group. In nature they catalyse the hydrolysis of triglycerides and other long chain fats and oils. Besides their normal substrates most lipases accept a very broad range of acyl donors and acyl acceptors5. Since lipases generally exhibit mostly a high stability, accept a wide variety of substrates and have a wide occurrence in nature, they have become readily available and industrially applicable enzymes. They have current industrial applications as detergent enzymes, in food and paper technology and in the pharmaceutical and speciality chemicals industry5. In their natural reaction lipases operate at an oil/water interface and convert sparingly water soluble triglycerides. Therefore, it is perhaps not surprising that they exhibit high stability and activity in organic media. Whereas in aqueous media ester hydrolysis is the main reaction of a lipase, in non- aqueous media the reaction with other nucleophiles such as alcohols, esters, hydrogenperoxides, ammonia and amines becomes possible. 5 Introduction Asp O O H His N N H O Asp - Asp O O O O O Ser O O NH HN H H His O N O His N R N N O O Asp H O H O O Ser O O Ser O NH HN H HN His NH O N O O O N R Free ROAc H O Acyl enzyme enzyme intermediate - (with acyldonor) O O (with alcohol) Ser NH HN O O Tetrahedral intermediates Figure 1.3 Catalytic machanism of a lipase catalyzed esterification of a chiral alcohol with vinyl acetate as model acyl donor. The active site of a lipase consists of a catalytic triad of serine, histidine and aspartate. In most lipases a flexible lid of one or more short α helices covers this active site. In the open form the substrate (acyl donor) can enter the active site and bind with the serine to form the tetrahedral intermediate.
Load more

Recommended publications
  • “Polyols: a Primer for Dietetic Professionals” Is a Self-Study
    1 “Polyols: A primer for dietetic professionals” is a self-study module produced by the Calorie Control Council, an accredited provider of continuing professional education (CPE) for dietetic professionals by the Commission on Dietetic Registration. It provides one hour of level 1 CPE credit for dietetic professionals. The full text of the module is in the notes section of each page, and is accompanied by summary points and/or visuals in the box at the top of the page. Directions for obtaining CPE are provided at the end of the module. 2 After completing this module, dietetic professionals will be able to: • Define polyols. • Identify the various types of polyols found in foods. • Understand the uses and health effects of polyols in foods. • Counsel clients on how to incorporate polyols into an overall healthful eating pattern. 3 4 Polyols are carbohydrates that are hydrogenated, meaning that a hydroxyl group replaces the aldehyde or ketone group found on sugars. Hydrogenated monosaccharides include erythritol, xylitol, sorbitol, and mannitol. Hydrogenated disaccharides include lactitol, isomalt, and maltitol. And hydrogenated starch hydrolysates (HSH), or polyglycitols (a wide range of corn syrups and maltodextrins), are formed from polysaccharides (Grabitske and Slavin 2008). 5 Nearly 54 percent of Americans are trying to lose weight, more than ever before. Increasingly, they are turning toward no- and low-sugar, and reduced calorie, foods and beverages to help them achieve their weight loss goals (78% of Americans who are trying to lose weight) (CCC 2010). Polyols, found in many of these foods, are becoming a subject of more interest. 6 They are incompletely digested , therefore are sometimes referred to as “low- digestible carbohydrates.” Polyols are not calorie free, as there is some degree of digestion and absorption of the carbohydrate.
    [Show full text]
  • Dental and Metabolic Effects of Lactitol in the Diet of Laboratory Rats
    Downloaded from British Journal of Nutrition (1989), 61, 17-24 17 https://www.cambridge.org/core Dental and metabolic effects of lactitol in the diet of labolratory rats BY T. H. GRENBY AND A. PHILLIPS Department of Oral Medicine and Pathology, United Medical and Dental Schools, Guy’s Hospital, London SEI 9RT . IP address: (Received 17 May 1988 - Accepted 30 August 1988) 170.106.35.93 I. Because so little is known about the properties of lactitol as a possible alternative bulk sweetener to sucrose, it was tested in two large-scale experiments in laboratory rats. Matched groups of caries-active Osborne-Mendel rats were fed.on uniform diets containing lactitol and compared with a sucrose control in both experiments, plus a xylitol control in the first experiment. , on 2. In the early stages of the experiments weight gains and food utilization were better on the Sucrose than on 26 Sep 2021 at 05:12:03 the lactitol regimens. Body-fat storage was higher on the sucrose than on the polyol regimens. 3. At the end of 8 weeks the mandibular molars were examined for dental plaque accumulation and dental caries. The dental caries scores when 160 g sucrose/kg in the diet was replaced by lactitol were lower by a highly significant margin, bringing them down to the same low level as those on a 160 g xylitol/kg regimen. 4. Testing lactitol in a manufactured food product, shortbread biscuits, in comparison with ordinary sucrose biscuits, showed differences in plaque scores (significant) and caries levels (highly significant), with 60 % fewer lesions on the lactitol regimen.
    [Show full text]
  • Polyols Have a Variety of Functional Properties That Make Them Useful Alternatives to Sugars in Applications Including Baked Goods
    Polyols have a variety of functional properties that make them useful alternatives to sugars in applications including baked goods. Photo © iStockphoto.com/Synergee pg 22 09.12 • www.ift.org BY LYN NABORS and THERESA HEDRICK SUGAR REDUCTION WITH Polyols Polyols are in a unique position to assist with reduced-sugar or sugar-free reformulations since they can reduce calories and complement sugar’s functionality. ugar reduction will be an important goal over the of the product’s original characteristics may still be main- next few years as consumers, government, and in- tained with the replacement of those sugars by polyols. Sdustry alike have expressed interest in lower-calorie In addition, excellent, good-tasting sugar-free products and lower-sugar foods. The 2010 Dietary Guidelines for can be developed by using polyols. Polyols are in a unique Americans put a strong emphasis on consuming fewer position to assist with reduced-sugar or sugar-free refor- calories and reducing intake of added sugars. The In- mulations; since they are only partially digested and ab- stitute of Medicine (IOM) held a public workshop in sorbed, they can reduce calories and complement sugar’s November 2010 to discuss ways the food industry can functionality. Polyols provide the same bulk as sugars and use contemporary and innovative food processing tech- other carbohydrates. Additionally, polyols have a clean, nologies to reduce calorie intake in an effort to reduce sweet taste, which is important since consumers are not and prevent obesity, and in October 2011 recommended likely to sacrifice taste for perceived health benefits. Poly- front-of-package labeling that includes rating the product ols have a host of other functional properties that make based on added sugars content.
    [Show full text]
  • Sweet Sensations by Judie Bizzozero | Senior Editor
    [Confections] July 2015 Sweet Sensations By Judie Bizzozero | Senior Editor By R.J. Foster, Contributing Editor For many, terms like “reduced-sugar” or “sugar-free” do not go with the word “candy.” And yet, the confectionery industry is facing growing demand for treats that offer the taste people have grown to love without the adverse health effects they’re looking to avoid. Thankfully, there is a growing palette of ingredients from which candy makers can paint a new picture of sweetness that will be appreciated by the even most discerning of confectionery critics. SUGAR ALCOHOLS Also referred to as polyols, sugar alcohols are a common ingredient in reduced-sugar and sugar-free applications, especially confections. Funny thing, they’re not sugars or alcohols. Carbohydrate chains composed of monomeric, dimeric and polymeric units, polyols resemble both sugars and alcohols, but do not contain an ethanol molecule. All but two sugar alcohols are less sweet than sugar. Being only partially digestible, though, replacing a portion of a formulation’s sugar with a sugar alcohol reduces total calories without losing bulk (which can occur when replacing sugar with high-intensity sweeteners). Unique flavoring, texturizing and moisture-controlling effects also make polyols well-suited for confectionery products. Two very common and very similar monomeric polyols are sorbitol and mannitol. Present in a variety of fruits and vegetables, both are derived from products of cornstarch hydrolysis. Sorbitol is made via hydrogenation of glucose, which is why sorbitol is sometimes referred to as glucitol. Mannitol is created when fructose hydrogenation converts fructose into mannose, for which the final product, mannitol, is named.
    [Show full text]
  • Lactitol, Bulk Sweetener for Sugar Free and Reduced Calories Hard
    Sugar Free Dental Properties Lactitol is noncariogenic. It is not fermented by the oral micro flora, so its consumption does not lead to Lactitol, Bulk Sweetener for the formation of acids that deminer- alize the tooth enamel. Also, the building up of tooth plaque is much less for lactitol-containing hard can- dies when compared to sugar. Its Sugar Free and Reduced noncariogenic properties have been shown in various clinical trials (Grenby and Desai, 1988; Grenby, 1989; Grenby and Phillips, 1989; Grenby et al., 1989; van der Calories Hard Candy Hoeven, 1986). REGULATORY ASPECTS A self-affirmation petition for the Generally Recognized as Safe status of lactitol, submitted by Purac, was his paper will discuss the prop- intense sweetener like aspartame or accepted for filing by the Food and Terties, regulatory aspects, and acesulfame-K. The taste, sweetening power, and Drug Administration in September applications of lactitol in hard can- 1993. The safety of lactitol has been dies. Lactitol is a disaccharide sugar profile of such sweetener combina- tions are very close to those of substantiated by numerous animal alcohol made from lactose by cat- and human studies. This safety alytic hydrogenation. sucrose. Its clean sweet taste allows a superb flavor release. research has been reviewed by sev- eral international authoritative bod- BENEFITS OF LACTITOL Reduced Calories ies (JEFCA, 1983; EEC, 1984). The Taste The FDA allows the use of a self- joint FAO/WHO Committee on Lactitol has a clean, sweet, sugar- determined value of 2.0 kilocalorie Food Additives has approved lacti- like taste without an aftertaste. The per gram for lactitol.
    [Show full text]
  • Constipation in Adults Search Date October 2006 Frank Frizelle and Murray Barclay
    Dig . estive system disor Constipation in adults Search date October 2006 Frank Frizelle and Murray Barclay ABSTRACT INTRODUCTION: Although there are defined criteria for the diagnosis of constipation, in practice, diagnostic criteria are less rigid, and in part depend on the perception of normal bowel habit. Constipation is highly prevalent, with approximately 12 million general practitioner prescriptions for laxatives in England in 2001. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of non-drug interventions, and of other interventions, in adults with idiopathic chronic con- stipation? We searched: Medline, Embase, The Cochrane Library and other important databases up to October 2006 (BMJ Clinical evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 42 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: arachis oil, biofeedback, bisacodyl, cascara, docusate, exercise, glycerine suppositories, glycerol, high-fibre diet, increasing fluids, ispaghula husk, lactitol, lactulose, macrogols (polyethylene glycols), magnesium salts, methylcellulose, paraffin, phosphate enemas, seed oils, senna, sodium citrate enemas, sterculia. der QUESTIONS s What are the effects of non-drug interventions in adults with idiopathic chronic constipation?. 3 What are the effects of other treatments in adults with idiopathic chronic constipation?.
    [Show full text]
  • Comparative Modes of Action of Lactitol and Lactulose in the Treatment of Hepatic Encephalopathy
    Gut: first published as 10.1136/gut.28.3.255 on 1 March 1987. Downloaded from Guit, 1987, 28, 255-259 Comparative modes of action of lactitol and lactulose in the treatment of hepatic encephalopathy D H PATIL, D WESTABY, Y R MAHIDA, K R PALMER, R REES, M L CLARK, A M DAWSON, AND D B A SILK From the Department of Gastroenterology and Nutrition, Central Middlesex Hospital, London, and Department of Gastroenterology, St Bartholomew's Hospital, London SUMMARY Lactitol, an unabsorbed sugar with defined laxative threshold and superior taste properties has been suggested as an alternative to lactulose in the treatment of hepatic encephalopathy. In the present study we have compared the colonic metabolism of the two sugars using an in vitro faecal incubation system. Both sugars were readily metabolised by faecal bacteria producing volatile fatty acids and the metabolism was inhibited by neomycin. The effect of lactitol and lactulose on terminal ileal and colonic pH was monitored in six normal subjects using a radiotelemetry technique. Both sugars significantly lowered right colonic pH (basal -6 51±0.48 vs lactitol -563±0 50; lactulose -5*18±0*82, p<0.05). The pH of rest of the colon and terminal ileum was unaffected. Neomycin given concurrently with lactulose abolished acidification of right colon. As lactitol and lactulose have similar effects within the colon, lactitol would appear to have a role in the treatment of hepatic encephalopathy. As neomycin antagonises the effect of lactulose in the colon, its concurrent use may be less effective in the treatment of hepatic encephalopathy.
    [Show full text]
  • EUROPEAN PHARMACOPOEIA 10.0 Index 1. General Notices
    EUROPEAN PHARMACOPOEIA 10.0 Index 1. General notices......................................................................... 3 2.2.66. Detection and measurement of radioactivity........... 119 2.1. Apparatus ............................................................................. 15 2.2.7. Optical rotation................................................................ 26 2.1.1. Droppers ........................................................................... 15 2.2.8. Viscosity ............................................................................ 27 2.1.2. Comparative table of porosity of sintered-glass filters.. 15 2.2.9. Capillary viscometer method ......................................... 27 2.1.3. Ultraviolet ray lamps for analytical purposes............... 15 2.3. Identification...................................................................... 129 2.1.4. Sieves ................................................................................. 16 2.3.1. Identification reactions of ions and functional 2.1.5. Tubes for comparative tests ............................................ 17 groups ...................................................................................... 129 2.1.6. Gas detector tubes............................................................ 17 2.3.2. Identification of fatty oils by thin-layer 2.2. Physical and physico-chemical methods.......................... 21 chromatography...................................................................... 132 2.2.1. Clarity and degree of opalescence of
    [Show full text]
  • Sugar Alcohols Fact Sheet
    International Food Information Council Sugar Alcohols Fact Sheet September 2004 BACKGROUND Sugar alcohols or polyols, as they are also called, have a long history of use in a wide variety of foods. Recent technical advances have added to the range of sugar alcohols available for food use and expanded the applications of these sugar replacers in diet and health-oriented foods. They have been found useful in sugar-free and reduced-sugar products, in foods intended for individuals with diabetes, and most recently in new products developed for carbohydrate controlled eating plans. Sugar alcohols are neither sugars nor alcohols. They are carbohydrates with a chemical structure that partially resembles sugar and partially resembles alcohol, but they don’t contain ethanol as alcoholic beverages do. They are incompletely absorbed and metabolized by the body, and consequently contribute fewer calories. The polyols commonly used include sorbitol, mannitol, xylitol, maltitol, maltitol syrup, lactitol, erythritol, isomalt and hydrogenated starch hydrolysates. Their calorie content ranges from 1.5 to 3 calories per gram compared to 4 calories per gram for sucrose or other sugars. Most are approximately half as sweet as sucrose; maltitol and xylitol are about as sweet as sucrose. Sugar alcohols occur naturally in a wide variety of fruits and vegetables, but are commercially produced from other carbohydrates such as sucrose, glucose, and starch. Along with adding a sweet taste, polyols perform a variety of functions such as adding bulk and texture, providing a cooling effect or taste, inhibiting the browning that occurs during heating and retaining moisture in foods. While polyols do not actually prevent browning, they do not cause browning either.
    [Show full text]
  • Lactitol for Sugarfree Compressed Sweets
    Lactitol For Sugarfree Compressed Sweets Ria Van Hoef PURAC America, Inc. n the food industry different types of tablets are pro- tablets made with different direct compressible polyols. Iduced, such as mints and tabletop sweetener tablets. The water absorption of the tablets made with lactitol is A modern way to make tablets is direct compression. negligible, only 0.1 percent after nine days. The sorbitol The advantages of direct compression above other tablets reach, at these conditions, equilibrium at approx- methods are diverse and mentioned below: imately 2 percent. Because of the low hygroscopicity of • Reduction of costs, caused by reduction of processing lactitol tablets, the moisture barrier of the packaging can time and manufacturing steps. be low and high packaging costs can be avoided. • Ease of processing, without moisture and heat, because Another important issue in sugarfree confections is no granulation steps are necessary. the tooth-friendliness of the ingredients. The tooth- • Avoidance of high compaction pressures. friendliness can be measured with the Mühlemann test. Direct compression is a process, in which all the ingre- This test is developed for measuring the pH of the den- dients are mixed together in a powder blend and directly tal plaque. Based on this test a product may be called compressed into a tablet. It is possible to make sugarfree tooth friendly when the pH of the dental plaque does not tablets by direct compression. Suitable excipients can be drop below 5.7 within a 30 minute period after con- polyols (sugar alcohols), like sorbitol, mannitol or lac- sumption. In Figure 3 lactitol is compared with sucrose, titol.The newest direct compressible polyol is lactitol dc which shows lactitol as a very tooth-friendly ingredient.
    [Show full text]
  • Nutrition Bytes
    UCLA Nutrition Bytes Title Are There Healthy Sweeteners: The Effects of Sugar Substitutes on the Gut Microbiome Permalink https://escholarship.org/uc/item/6bs6b2zz Journal Nutrition Bytes, 20(1) ISSN 1548-4327 Author Yun, Lisa Publication Date 2016 Peer reviewed eScholarship.org Powered by the California Digital Library University of California Are There Healthy Sweeteners: The Effects of Sugar Substitutes on the Gut Microbiome Yun, Lisa, University of California, Los Angeles, David Geffen School of Medicine Keywords: Sugar Substitute, Gut Microbiome, artificial sugar, sweetener Abstract Objective: This study was designed to examine the effects of sugar substitutes on the gut microbiome. Methods: PUBMED was used to find articles that studied the gut microbiome after consumption of a sugar substitute in humans. Both observational and interventional studies were selected for this review. Results: Starting with 31 articles found on PUBMED, 5 articles were included to be reviewed after 26 articles were excluded. Three natural sugar substitutes and four categories of artificial sweeteners were studied. Maltitol, lactitol, and isomalt were the natural sugar substitutes, and aspartame, acesulfame-K, non-caloric artificial sweeteners, and saccharin were the artificial sweeteners. The outcomes for Bifidobacteria, Bacteroides, Clostridium, Lactobacilli, Fusobacterium prausnitzii, and Enterobacteriaceae were addressed. Natural sugar substitutes were seen to increase bacterial populations that are believed to be beneficial to humans while artificial sweeteners established bacterial populations that are considered harmful to health. Conclusions: The studies examined suggest cautious use of artificial sweeteners due to its effects on the gut microbiome while natural sugar substitutes could have potential health benefits. Introduction Sugar substitutes could allow for a lower calorie diet which is important considering the current obesity epidemic.
    [Show full text]
  • Polyols: Beyond Sweet Taste
    [Sweeteners] Vol. 17 No. 10 October 2007 Ww Polyols: Beyond Sweet Taste By: Robin Steagall and Lyn O’Brien Nabors Polyols are neither sugars nor alcohols. They are a group of low-digestible carbohydrates, similar in structure to sugar molecules, except for the substitution of a hydroxyl group in place of the aldehyde group found on sugars. This substitution is the reason polyols are commonly referred to as sugar alcohols. The substitution of a single hydroxyl group preserves enough of the chemical structure of sugar to give polyols many of the physical properties of sugars, so they can often replace sugar and corn sweeteners in many applications. The structural differences also impart special functional and health benefits to polyol-containing products. The health benefits were discussed in the April 2007 issue of Food Product Design. This provides an overview of the functional benefits of polyols. Physical properties Polyols and sugars have several physical properties that are important in food processing. Understanding the different physical and functional characteristics among polyols is key to selecting the best polyol for a food application. Sweetness. Ingredient sweetness is usually measured in relation to sucrose, which has a sweetness reference value of 1 or 100%. Polyol sweetness varies and depends in part on the application. Generally, polyols vary in sweetness from about half as sweet to equally as sweet as sucrose. Taste and flavor. Other components of flavor are the persistence of sweetness, presence or absence of aftertaste, and the sweetness profile. Polyols are nonreactive and easily combine with high-intensity sweeteners in sugar-free chewing gums, candies, frozen desserts and baked goods.
    [Show full text]