DOCSLIB.ORG

(12) Patent Application Publication (10) Pub. No.: US 2006/0135609 A1 Toone Et Al

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
(12) Patent Application Publication (10) Pub. No.: US 2006/0135609 A1 Toone Et Al US 20060135609A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0135609 A1 TOOne et al. (43) Pub. Date: Jun. 22, 2006 (54) OPHTHAMOLOGICAL DRUGS Related U.S. Application Data (75) Inventors: Eric J. Toone, Durham, NC (US); (60) Provisional application No. 60/620,320, filed on Oct. David L. Epstein, Bahama, NC (US); 21, 2004. Pratap Challa, Durham, NC (US); Philip W. Snyder, Cambridge, MA Publication Classification (US); Xin Chen, Chapel Hill, NC (US); Mitchell A. deLong, Raleigh, NC (US) (51) Int. Cl. A6II 3L/225 (2006.01) Correspondence Address: (52) U.S. Cl. .............................................................. 514/547 Michael Best & Friedrich LLP Suite 3300 (57) ABSTRACT 100 East Wisconsin Avenue The present invention relates generally to ophthamological drugs. More specifically, the inventon relates to a method of Milwaukee, WI 53202-4108 (US) modifying (derivatizing) ophthamological drugs so as to (73) Assignee: Duke University. Durham, NC increase their penetration through the cornea. The invention also relates to drugs modified (derivatized) in accordance (21) Appl. No.: 11/255,478 with the instant method and to the use of same in treating conditions associated with elevated intraocular pressure, (22) Filed: Oct. 21, 2005 particularly, glaucoma. 15.0 10.0 5. O -- OD (drug) -A-OS (control) Time (hours) Patent Application Publication Jun. 22, 2006 Sheet 1 of 10 US 2006/01 35609 A1 O O V O v ves O CN: Y O O ve O OO O O O Cs V O GN C eue Sequoy effueuo 96 Patent Application Publication Jun. 22, 2006 Sheet 2 of 10 US 2006/01 35609 A1 N v O GN O O V & C eue Sequoy efueuo % Patent Application Publication Jun. 22, 2006 Sheet 3 of 10 US 2006/01 35609 A1 ---NS.. D O S. O) E s C. C. O eue Sequoy efueuo % Patent Application Publication Jun. 22, 2006 Sheet 4 of 10 US 2006/01 35609 A1 ??? (6H uul) Ol Patent Application Publication Jun. 22, 2006 Sheet 5 of 10 US 2006/0135609 A1 SNst 9 d c o ? C u? O C O cy N N v r- O o C c o CO N N N N N N CN N N w wer ve v- ve- wo (6H uu) dOl Patent Application Publication Jun. 22, 2006 Sheet 6 of 10 US 2006/0135609 A1 5-O-Ribitol (2,3-dichloro-4-(thiophene-2-carbonyl)phenoxyacetate O C { Cl OH pH ory O N-N-N-t OH O OH 5 15 O 10 s 5 -5 s E E - -- 0 SS SS N- -10 Y-1 3. 3 -5 -15 -10 -20 -O-anolin -15 -O-anoin -O-tanolin + 10% ticrynafen -o-lanolin + 15% ticrynafen O 20 40 60 80 100 120 140 160 O 20 40 60 80 100 120 140 160 time (hours) time (hours) 10% 15% IOP reduction from baseline, IOP reduction from baseline, mmHg mmHg time control ticrynafen control ticrynafen ---------- - = 4 (n=4) (n 4) baseline 23.6 23.4 21.9 22.2 24 hrs 21.1 (-2.3) 20.6 (-2.8) 22.8 (+0.9) 23.2 (+1.0) 48 hrs 22.4 (-l.2) 21.0 (-2.4) 21.8 (-0.1) 21.0 (-1.2 72 hrs 20.3 (-3.3) 19.9 (-3.5) 20.3 (-1.6) 20.6 (-1.6) 6 days 22.2 (-1.4 22.0 (-1.6) 24.3 (-2.4 23.7 (+1.5) FIG. 6 Patent Application Publication Jun. 22, 2006 Sheet 8 of 10 US 2006/01 35609 A1 5-O-(90.1 lo, 15R)-15-2-Benzo[b]thiophen-2-yl)-16, 17, 18,19,20-pentanor 5,6,13,14-tetrahydro-9,11,15-trihydroxyprostanoylxylitol Cl D oH ÖH S Hd dH 23.0 22.5 0.004% 22.0 IOP reduction from untreated 21.5 control, mmHg 21.0 time (n= 4) 20.5 - W / I O y f -- TTDay 0 -0.3orror-r---------------- 20.0 Day 1 -0.8 Day 2 -1.3 19.5 k Day 3 -1.5 19.0 k Day 5 -0.7 18.5 Day 7 -1.5 -O-- untreated Day 10 -0.1 18.0 -O- + O.O.04% Day 11 -1.0 17.5 Day 12 -0.8 17.0 t Day 14 -0.1 0 2 4 6 10 12 14 Time (days) FIG. 8 Patent Application Publication Jun. 22, 2006 Sheet 9 of 10 US 2006/0135609 A1 l-O-((9o, Ilo, 15R)-15-(2-Benzo(blthiophen-2-yl)- 5 16, 17, 18,19,20-pentanor-5,6,13, 1 4-tetrahydro-9, -0-0.004% -0- 0.02% 11, 15-trihydroxyprostanoyl-11-hydroxy-3,6,9- trioxaundecane HO OH -20 0 20 40 60 80 100 120 time (hours) 0.004% OP 0.02% IOP Change IOP (Change from Baseline), Change IOP (Change from Baseline), from mmHg from mmHg Untreated Untreated Control, Control, mmHg -ms time untreated treated untreated treated (n=4) (n-4) (n=4) (n= 4) Day 1 morning 24.0+0.8 (0) 24.0+09 (0) 0. 18.1t1.2 (0) 17.5tl.8 (0) -0.6 afternoon 25.1+0.5 (+1.1) 22.3+0.4 (-1.7) -2.8 17.3t 1.2 (-0.8) 14.5it1.3 (-3.0) -2.8 Day 2 morning 25.5-0.7 (+1.5) 23.3+0.6 (-0.7) -2.2 18.0t:0.9 (-0.1) 16.5+0.7 (-1.0) -1.5 afternoon 24.1+0.9 (+0.1). 22.4+0.7 (-1.6) -1.7 17.6+1.2 (-0.5) 15.2+1.3 (-2.3) -2.4 Day 3 morning 24.20.7 (+0.2). 22.8+0.8 (-1.2) -1.4 17.6+1.4 (-0.5) 15.8+1.0 (-17) -1.8 afternoon 25.1+0.7 (+1.1) 23.5+0.6 (-0.5) -1.6 17.6tl.2 (-0.5) 15.3tl.3 (-2.2) -2.3 Day 4 morning 24.0tl.2 (0) 22.0+0.9 (-2.0) -2.0 17.2+0.9 (-0.9) 15.8+10 (-1.7) -14 afternoon 23.2+0.4 (-0.8) 22.0+0.3 (-2.0) -1.2 19.8+1.1 (+1.7) 16.8+09 (-0.7) -3.0 Day 5 morning 23.3+0.6 (-0.7) 22.1+0.7 (-1.9) -12 18.5:1.1 (+0.4) 16.5-0.9 (-1,0) -2.0 afternoon. 24.9.7 (+0.9) 23.00.3 (-2.0) -19 17.8+0.8 (-0.3) 15.9+0.9 (-1.6) -19 FIG. 9 US 2006/01 35609 A1 Jun. 22, 2006 OPHTHAMOLOGICAL DRUGS resistance of the nerve tissue to damage, and the compliance of connective tissue surrounding and Supporting the optic CROSS-REFERENCE TO RELATED nerve. One agent, Memantine, is in phase III clinical trials APPLICATIONS (Allergan) as an agent that may prove to be neuroprotective. 0001. This application claims priority under 35 U.S.C. 0008. The topical application of ophthamological drugs S119(e) to U.S. Provisional Patent Application No. 60/620, for the treatment of glaucoma requires penetration of the 320 filed Oct. 21, 2004, the entire content of which is hereby drug through the cornea and into the anterior chamber, incorporated by reference. which contains aqueous humor, which then drains into the conventional outflow pathway (trabecular meshwork and TECHNICAL FIELD Schlemm's canal) and the uveal-scleral pathway (unconven 0002 The present invention relates, in general, to oph tional outflow pathway). Intraocular pressure is lowered by thamological drugs, and, in particular, to a method of drugs acting in the trabecular meshwork/Schlemm's canal modifying ophthamological drugs so as to increase their and the uveal-scleral pathway. Penetration of the drug penetration through the cornea into the anterior chamber. through the cornea requires a balance of hydrophobic and The invention further relates to such modified drugs and to hydrophilic characteristics. The drug must be sufficiently the use of same in treating diseases/disorders of the eye, soluble in non-polar media to diffuse into the cornea and Such as glaucoma and other conditions related to elevated sufficiently soluble in polar (aqueous) media to diffuse out of intraocular pressure. the cornea into the aqueous humor. BACKGROUND 0009. Many drugs potentially useful for the treatment of glaucoma are carboxylic acids (e.g., phenoxyacetic acids or 0003 Glaucoma is one of the three leading causes of cinnaminic acids). Carboxylic acids are typically delivered blindness in the United States and a leading cause of in buffered aqueous solution; near neutral pH, carboxylic blindness in the world. Over 2.2 million people in the United acids exist as the deprotonated carboxylate salt. Ionized States have glaucoma, and several million more are at risk carboxylate salts, while soluble in aqueous Solution, will not of developing the disease. As the population ages, the penetrate the cornea. Such drugs can be delivered as pro number of individuals with glaucoma will continue to grow drug esters. The use of pro-drug esters, which are cleaved since glaucoma affects the oldest individuals disproportion enzymatically (e.g., in the cornea) to regenerate the active ately. compound, can enhance penetration of drug through the 0004 Glaucoma is not just one disease, rather, it is a cornea into the anterior chamber. spectrum of conditions that share a final common pathway 0010 Unfortunately, many esters are too hydrophobic of acquired, progressive deterioration of the neuronal com (non-polar) to diffuse out of the relatively non-polar external ponents of the optic nerve.
Load more

Recommended publications
  • Aldrich FT-IR Collection Edition I Library
    Aldrich FT-IR Collection Edition I Library Library Listing – 10,505 spectra This library is the original FT-IR spectral collection from Aldrich. It includes a wide variety of pure chemical compounds found in the Aldrich Handbook of Fine Chemicals. The Aldrich Collection of FT-IR Spectra Edition I library contains spectra of 10,505 pure compounds and is a subset of the Aldrich Collection of FT-IR Spectra Edition II library. All spectra were acquired by Sigma-Aldrich Co. and were processed by Thermo Fisher Scientific. Eight smaller Aldrich Material Specific Sub-Libraries are also available. Aldrich FT-IR Collection Edition I Index Compound Name Index Compound Name 3515 ((1R)-(ENDO,ANTI))-(+)-3- 928 (+)-LIMONENE OXIDE, 97%, BROMOCAMPHOR-8- SULFONIC MIXTURE OF CIS AND TRANS ACID, AMMONIUM SALT 209 (+)-LONGIFOLENE, 98+% 1708 ((1R)-ENDO)-(+)-3- 2283 (+)-MURAMIC ACID HYDRATE, BROMOCAMPHOR, 98% 98% 3516 ((1S)-(ENDO,ANTI))-(-)-3- 2966 (+)-N,N'- BROMOCAMPHOR-8- SULFONIC DIALLYLTARTARDIAMIDE, 99+% ACID, AMMONIUM SALT 2976 (+)-N-ACETYLMURAMIC ACID, 644 ((1S)-ENDO)-(-)-BORNEOL, 99% 97% 9587 (+)-11ALPHA-HYDROXY-17ALPHA- 965 (+)-NOE-LACTOL DIMER, 99+% METHYLTESTOSTERONE 5127 (+)-P-BROMOTETRAMISOLE 9590 (+)-11ALPHA- OXALATE, 99% HYDROXYPROGESTERONE, 95% 661 (+)-P-MENTH-1-EN-9-OL, 97%, 9588 (+)-17-METHYLTESTOSTERONE, MIXTURE OF ISOMERS 99% 730 (+)-PERSEITOL 8681 (+)-2'-DEOXYURIDINE, 99+% 7913 (+)-PILOCARPINE 7591 (+)-2,3-O-ISOPROPYLIDENE-2,3- HYDROCHLORIDE, 99% DIHYDROXY- 1,4- 5844 (+)-RUTIN HYDRATE, 95% BIS(DIPHENYLPHOSPHINO)BUT 9571 (+)-STIGMASTANOL
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2009/0156618 A1 Tollefson (43) Pub
    US 20090156618A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/0156618 A1 Tollefson (43) Pub. Date: Jun. 18, 2009 (54) 1-(1-(2-ETHOXYETHYL)-3-ETHYL-7- Related U.S. Application Data (4-METHYLPYRIDIN-2-YLAMINO) - 1H-PYRAZOLO 4.3-D PYRIMIDIN-5-YL) (60) Provisional application No. 60/735,320, filed on Nov. PPERDINE-4-CARBOXYLIC ACID AND 10, 2005. SALTS THEREOF Publication Classification (51) Int. Cl. (75) Inventor: Michael B. Tollefson, Dardenne A 6LX 3/59 (2006.01) Prairie, MO (US) C07D 487/04 (2006.01) A6IP 9/12 (2006.01) A6IP 25/00 (2006.01) Correspondence Address: A6IP 9/00 (2006.01) PFZER INC. PATENT DEPARTMENT, Bld 114 M/S 114, (52) U.S. Cl. ...................................... 514/262.1; 54.4/262 EASTERN PONT ROAD (57) ABSTRACT GROTON, CT 06340 (US) The present invention comprises 1-(1-(2-ethoxyethyl)-3- ethyl-7-(4-methylpyridin-2-ylamino)-1H-pyrazolo 4.3-d (73) Assignee: Pfizer Inc pyrimidin-5-yl)piperidine-4-carboxylic acid and its salts. The invention further comprises pharmaceutical composi tions, methods of treatment, and synthetic methods relating to (21) Appl. No.: 111558,306 1-(1-(2-ethoxyethyl)-3-ethyl-7-(4-methylpyridin-2- ylamino)-1H-pyrazolo 4.3-dipyrimidin-5-yl)piperidine-4- (22) Filed: Nov. 9, 2006 carboxylic acid and its salts. Patent Application Publication Jun. 18, 2009 Sheet 2 of 2 US 2009/0156618 A1 "SOIHZ US 2009/0156618 A1 Jun. 18, 2009 1-(1-(2-ETHOXYETHYL)-3-ETHYL-7- 1H-pyrazolo 4,3-dipyrimidin-5-yl)piperidine-4-carboxylic (4-METHYLPYRIDIN-2-YLAMINO) - acid and its pharmaceutically acceptable salts.
    [Show full text]
  • Campro Catalog Stable Isotope
    Introduction & Welcome Dear Valued Customer, We are pleased to present to you our Stable Isotopes Catalog which contains more than three thousand (3000) high quality labeled compounds. You will find new additions that are beneficial for your research. Campro Scientific is proud to work together with Isotec, Inc. for the distribution and marketing of their stable isotopes. We have been working with Isotec for more than twenty years and know that their products meet the highest standard. Campro Scientific was founded in 1981 and we provide services to some of the most prestigious universities, research institutes and laboratories throughout Europe. We are a research-oriented company specialized in supporting the requirements of the scientific community. We are the exclusive distributor of some of the world’s leading producers of research chemicals, radioisotopes, stable isotopes and environmental standards. We understand the requirements of our customers, and work every day to fulfill them. In working with us you are guaranteed to receive: - Excellent customer service - High quality products - Dependable service - Efficient distribution The highly educated staff at Campro’s headquarters and sales office is ready to assist you with your questions and product requirements. Feel free to call us at any time. Sincerely, Dr. Ahmad Rajabi General Manager 180/280 = unlabeled 185/285 = 15N labeled 181/281 = double labeled (13C+15N, 13C+D, 15N+18O etc.) 186/286 = 12C labeled 182/282 = d labeled 187/287 = 17O labeled 183/283 = 13C labeleld 188/288 = 18O labeled 184/284 = 16O labeled, 14N labeled 189/289 = Noble Gases Table of Contents Ordering Information.................................................................................................. page 4 - 5 Packaging Information ..............................................................................................
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2007/0254920 A1 Delong Et Al
    US 20070254920A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2007/0254920 A1 deLong et al. (43) Pub. Date: Nov. 1, 2007 (54) PRODRUG DERIVATIVES OF ACIDS USING (52) U.S. Cl. ......................... 514/319; 514/323: 514/573; ALCOHOLS WITH HOMOTOPIC HYDROXY 514/415: 514/443; 514/469; GROUPS AND METHODS FOR THEIR 546/196; 546/201: 546/206; PREPARATION AND USE 548/495; 549/49; 549/462 (75) Inventors: Mitchell A. deLong, Raleigh, NC (US); (57) ABSTRACT Jill M. McFadden, Chapel Hill, NC This invention relates to novel homotopic prodrugs and (US); Susan M. Royalty, Cary, NC medicaments and methods for their preparation, testing and (US); Eric J. Toone, Durham, NC use. In one embodiment, the homotopic prodrug has the (US); Jeffrey D. Yingling, Apex, NC general formula (US) Correspondence Address: O MICHAEL BEST & FRIEDRCH LLP 100 E WISCONSNAVENUE Rb, Suite 3300 --- MILWAUKEE, WI 53202 (US) wherein (73) Assignee: Aerie Pharmaceuticals, Inc., Research Triangle Park, NC (21) Appl. No.: 11/412,207 (22) Filed: Apr. 26, 2006 -- Publication Classification is a biologically-active moiety comprising a carboxylic acid functional group, and R is a homotopically-symmetrical (51) Int. Cl. alcohol bonded to the biologically-active moiety through the A6 IK 3/558 (2006.01) carboxylic acid functional group to form an ester linkage, as CO7D 409/02 (2006.01) well as optical isomers, enantiomers, pharmaceutically CO7D 405/02 (2006.01) acceptable salts, biohydrolyzable amides, esters, and imides CO7D 403/02 (2006.01) thereof and combinations thereof. US 2007/0254920 A1 Nov. 1, 2007 PRODRUG DERVATIVES OF ACDS USING WO 99/12896, and WO 99/12898.) However, such modifi ALCOHOLS WITH HOMOTOPIC HYDROXY cations have either resulted in only modest increases in GROUPS AND METHODS FOR THEIR half-life or resulted in compounds with diminished potency.
    [Show full text]
  • (12) United States Patent (10) Patent No.: US 7,304,086 B2 Schilling Et Al
    USOO7304086B2 (12) United States Patent (10) Patent No.: US 7,304,086 B2 Schilling et al. (45) Date of Patent: *Dec. 4, 2007 (54) INHIBITORS OF GLUTAMINYL CYCLASE WO WOOO,53596 9, 2000 WO WO O1/34594 A1 5, 2001 (75) Inventors: Stephan Schilling, Halle/Saale (DE); WO WO O2, 13821 2, 2002 WO WO O2, 16318 A1 2, 2002 Mirko Buchholz, Halle/Saale (DE): WO WO O2O16318 A1 * 2/2002 Andre Johannes Niestroj, Sennewitz WO WO O2/O66459 A1 8, 2002 (DE); Ulrich Heiser, Halle/Saale (DE): WO WO O2/O92103 A1 11 2002 Hans-Ulrich Demuth, Halle/Saale (DE) WO WO O2O94813 A1 * 11/2002 WO WO 03/04.0174 A2 5, 2003 (73) Assignee: Probiodrug AG, Halle/Saale (DE) WO WO O3,O70732 8, 2003 WO WO O3068738 8, 2003 (*) Notice: Subject to any disclaimer, the term of this WO WO O30954.21 A1 * 11/2003 patent is extended or adjusted under 35 WO WO 2004O26815 A2 * 4, 2004 U.S.C. 154(b) by 20 days. WO WO 2004/089366 10, 2004 WO WO 2004/098591 A2 11 2004 This patent is Subject to a terminal dis WO WO 2004/098.625 A2 11 2004 claimer. OTHER PUBLICATIONS (21) Appl. No.: 11/051,760 Haley et al. Giorn. Ital. Chemioterap. (1962) 6-9 (No. 3), 213-24. Abstract from CAS attached. (22) Filed: Feb. 4, 2005 Hough et al. Pharmacology, Biochemistry and Behavior 1999, 65(1), 61-66. * Abstract from CAS attached.* (65) Prior Publication Data Morissette et al. Advanced Drug Delivery Reviews 2004, 56. US 2005/0215573 A1 Sep.
    [Show full text]
  • Benzyl-L-Threitol
    A Publication of Reliable Methods for the Preparation of Organic Compounds Working with Hazardous Chemicals The procedures in Organic Syntheses are intended for use only by persons with proper training in experimental organic chemistry. All hazardous materials should be handled using the standard procedures for work with chemicals described in references such as "Prudent Practices in the Laboratory" (The National Academies Press, Washington, D.C., 2011; the full text can be accessed free of charge at http://www.nap.edu/catalog.php?record_id=12654). All chemical waste should be disposed of in accordance with local regulations. For general guidelines for the management of chemical waste, see Chapter 8 of Prudent Practices. In some articles in Organic Syntheses, chemical-specific hazards are highlighted in red “Caution Notes” within a procedure. It is important to recognize that the absence of a caution note does not imply that no significant hazards are associated with the chemicals involved in that procedure. Prior to performing a reaction, a thorough risk assessment should be carried out that includes a review of the potential hazards associated with each chemical and experimental operation on the scale that is planned for the procedure. Guidelines for carrying out a risk assessment and for analyzing the hazards associated with chemicals can be found in Chapter 4 of Prudent Practices. The procedures described in Organic Syntheses are provided as published and are conducted at one's own risk. Organic Syntheses, Inc., its Editors, and its Board of Directors do not warrant or guarantee the safety of individuals using these procedures and hereby disclaim any liability for any injuries or damages claimed to have resulted from or related in any way to the procedures herein.
    [Show full text]
  • Ion Channels
    UC Davis UC Davis Previously Published Works Title THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels. Permalink https://escholarship.org/uc/item/1442g5hg Journal British journal of pharmacology, 176 Suppl 1(S1) ISSN 0007-1188 Authors Alexander, Stephen PH Mathie, Alistair Peters, John A et al. Publication Date 2019-12-01 DOI 10.1111/bph.14749 License https://creativecommons.org/licenses/by/4.0/ 4.0 Peer reviewed eScholarship.org Powered by the California Digital Library University of California S.P.H. Alexander et al. The Concise Guide to PHARMACOLOGY 2019/20: Ion channels. British Journal of Pharmacology (2019) 176, S142–S228 THE CONCISE GUIDE TO PHARMACOLOGY 2019/20: Ion channels Stephen PH Alexander1 , Alistair Mathie2 ,JohnAPeters3 , Emma L Veale2 , Jörg Striessnig4 , Eamonn Kelly5, Jane F Armstrong6 , Elena Faccenda6 ,SimonDHarding6 ,AdamJPawson6 , Joanna L Sharman6 , Christopher Southan6 , Jamie A Davies6 and CGTP Collaborators 1School of Life Sciences, University of Nottingham Medical School, Nottingham, NG7 2UH, UK 2Medway School of Pharmacy, The Universities of Greenwich and Kent at Medway, Anson Building, Central Avenue, Chatham Maritime, Chatham, Kent, ME4 4TB, UK 3Neuroscience Division, Medical Education Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY, UK 4Pharmacology and Toxicology, Institute of Pharmacy, University of Innsbruck, A-6020 Innsbruck, Austria 5School of Physiology, Pharmacology and Neuroscience, University of Bristol, Bristol, BS8 1TD, UK 6Centre for Discovery Brain Science, University of Edinburgh, Edinburgh, EH8 9XD, UK Abstract The Concise Guide to PHARMACOLOGY 2019/20 is the fourth in this series of biennial publications. The Concise Guide provides concise overviews of the key properties of nearly 1800 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties.
    [Show full text]
  • Bio-Based Chemicals from Renewable Biomass for Integrated Biorefineries
    energies Review Bio-Based Chemicals from Renewable Biomass for Integrated Biorefineries Kirtika Kohli 1 , Ravindra Prajapati 2 and Brajendra K. Sharma 1,* 1 Prairie Research Institute—Illinois Sustainable Technology Center, University of Illinois, Urbana Champaign, IL 61820, USA; [email protected] 2 Conversions & Catalysis Division, CSIR-Indian Institute of Petroleum, Dehradun, Uttarakhand 248005, India; [email protected] * Correspondence: [email protected] Received: 10 December 2018; Accepted: 4 January 2019; Published: 13 January 2019 Abstract: The production of chemicals from biomass, a renewable feedstock, is highly desirable in replacing petrochemicals to make biorefineries more economical. The best approach to compete with fossil-based refineries is the upgradation of biomass in integrated biorefineries. The integrated biorefineries employed various biomass feedstocks and conversion technologies to produce biofuels and bio-based chemicals. Bio-based chemicals can help to replace a large fraction of industrial chemicals and materials from fossil resources. Biomass-derived chemicals, such as 5-hydroxymethylfurfural (5-HMF), levulinic acid, furfurals, sugar alcohols, lactic acid, succinic acid, and phenols, are considered platform chemicals. These platform chemicals can be further used for the production of a variety of important chemicals on an industrial scale. However, current industrial production relies on relatively old and inefficient strategies and low production yields, which have decreased their competitiveness with fossil-based alternatives. The aim of the presented review is to provide a survey of past and current strategies used to achieve a sustainable conversion of biomass to platform chemicals. This review provides an overview of the chemicals obtained, based on the major components of lignocellulosic biomass, sugars, and lignin.
    [Show full text]
  • Sugar Alcohols a Sugar Alcohol Is a Kind of Alcohol Prepared from Sugars
    Sweeteners, Good, Bad, or Something even Worse. (Part 8) These are Low calorie sweeteners - not non-calorie sweeteners Sugar Alcohols A sugar alcohol is a kind of alcohol prepared from sugars. These organic compounds are a class of polyols, also called polyhydric alcohol, polyalcohol, or glycitol. They are white, water-soluble solids that occur naturally and are used widely in the food industry as thickeners and sweeteners. In commercial foodstuffs, sugar alcohols are commonly used in place of table sugar (sucrose), often in combination with high intensity artificial sweeteners to counter the low sweetness of the sugar alcohols. Unlike sugars, sugar alcohols do not contribute to the formation of tooth cavities. Common Sugar Alcohols Arabitol, Erythritol, Ethylene glycol, Fucitol, Galactitol, Glycerol, Hydrogenated Starch – Hydrolysate (HSH), Iditol, Inositol, Isomalt, Lactitol, Maltitol, Maltotetraitol, Maltotriitol, Mannitol, Methanol, Polyglycitol, Polydextrose, Ribitol, Sorbitol, Threitol, Volemitol, Xylitol, Of these, xylitol is perhaps the most popular due to its similarity to sucrose in visual appearance and sweetness. Sugar alcohols do not contribute to tooth decay. However, consumption of sugar alcohols does affect blood sugar levels, although less than that of "regular" sugar (sucrose). Sugar alcohols may also cause bloating and diarrhea when consumed in excessive amounts. Erythritol Also labeled as: Sugar alcohol Zerose ZSweet Erythritol is a sugar alcohol (or polyol) that has been approved for use as a food additive in the United States and throughout much of the world. It was discovered in 1848 by British chemist John Stenhouse. It occurs naturally in some fruits and fermented foods. At the industrial level, it is produced from glucose by fermentation with a yeast, Moniliella pollinis.
    [Show full text]
  • The Generation and Reactivity of Organozinc Carbenoids
    The Generation and Reactivity of Organozinc Carbenoids A Thesis Presented by Caroline Joy Nutley In Partial Fulfilment of the Requirements for the Award of the Degree DOCTOR OF PHILOSOPHY of the UNIVERSITY OF LONDON Christopher Ingold Laboratories Department of Chemistry University College London London WCIH OAJ September 1995 ProQuest Number: 10016731 All rights reserved INFORMATION TO ALL USERS The quality of this reproduction is dependent upon the quality of the copy submitted. In the unlikely event that the author did not send a complete manuscript and there are missing pages, these will be noted. Also, if material had to be removed, a note will indicate the deletion. uest. ProQuest 10016731 Published by ProQuest LLC(2016). Copyright of the Dissertation is held by the Author. All rights reserved. This work is protected against unauthorized copying under Title 17, United States Code. Microform Edition © ProQuest LLC. ProQuest LLC 789 East Eisenhower Parkway P.O. Box 1346 Ann Arbor, Ml 48106-1346 Through doubting we come to questioning and through questioning we come to the truth. Peter Abelard, Paris, 1122 Abstract This thesis concerns an investigation into the generation and reactivity of organozinc carbenoids, from both a practical and mechanistic standpoint, using the reductive deoxygenation of carbonyl compounds with zinc and a silicon electrophile. The first introductory chapter is a review of organozinc carbenoids in synthesis. The second chapter opens with an overview of the development of the reductive deoxygenation of carbonyl compounds with zinc and a silicon electrophile since its inception in 1973. The factors influencing the generation of the zinc carbenoid are then investigated using a control reaction, and discussed.
    [Show full text]
  • A Simple Synthesis of 2-Keto-3-Deoxy-D-Erythro-Hexonic
    A simple synthesis of 2-keto-3-deoxy-D-erythro-hexonic acid isopropyl ester, a key sugar for the bacterial population living under metallic stress Claire Grison, Brice-Loïc Renard, Claude Grison To cite this version: Claire Grison, Brice-Loïc Renard, Claude Grison. A simple synthesis of 2-keto-3-deoxy-D-erythro- hexonic acid isopropyl ester, a key sugar for the bacterial population living under metallic stress. Bioorganic Chemistry, Elsevier, 2014, 52, pp.50-55. 10.1016/j.bioorg.2013.11.006. hal-03149058 HAL Id: hal-03149058 https://hal.archives-ouvertes.fr/hal-03149058 Submitted on 15 Mar 2021 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. A simple synthesis of 2-keto-3-deoxy-D-erythro-hexonic acid isopropyl ester, a key sugar for the bacterial population living under metallic stress ⇑ Claire M. Grison a, , Brice-Loïc Renard b, Claude Grison b a ICMMO UMR 8182, Equipe Synthèse Organique & Méthodologie, Université Paris Sud, Bât. 420, 15 rue Georges Clémenceau, 91405 Orsay cedex, France b CEFE UMR 5175, Campus CNRS, 1919 route de Mende, 34293 Montpellier cedex 5, France abstract 2-Keto-3-deoxy-D-erythro-hexonic acid (KDG) is the key intermediate metabolite of the Entner Doudoroff (ED) pathway.
    [Show full text]
  • Evaluation of Fundamental Characteristics of D-Threitol As
    Evaluation of fundamental characteristics of D-Threitol as phase change material at high temperature On Line Number 790 Hideto Hidaka,1 Masanori Yamazaki,1 Masayoshi Yabe,1 Hiroyuki Kakiuchi,1 Erwin P. Ona,2 Yoshihiro Kojima3 and Hitoki Matsuda2 1 Mitsubishi Chemical Group Science and Technology Research Center, Toho-Cho 1, Yokkaichi, Mie 540-8530, Japan, [email protected] 2 Department of Chemical Engineering, Nagoya University, Furo-Cho, Chikusa, Aichi 464-8630, Japan 3 Research Center for Advanced Waste and Emission Management, Nagoya University, Furo-Cho, Chikusa, Aichi 464-8630, Japan ABSTRACT This study focused on polyalcohols as phase change material, which stores a large amount of latent heat at high temperature. D-Threitol, which is an isomer of meso-Erythritol, was studied to obtain its phase change characteristics by means of DSC analysis and a lab-scale heating and cooling apparatus. Usability of D-Threitol as phase change material was evaluated by comparison with other polyalocohols. It was found that D-Threitol started to melt at around 90 degrees C with a relatively large latent heat of 225 kJ/kg. On the other hand, D-Threitol started solidification when the temperature was cooled between at 40 degrees C and 46 degrees C, indicated by a rapid rise to 89 degrees C in a lab-scale heating and cooling apparatus. It was then considered that D-Threitol was applicable as an environmental-friendly PCM for a hot water supply. KEYWORDS Phase change materials, Polyalcohols, Threitol INTRODUCTION Latent heat storage by Phase Change Materials (PCMs) has the advantage to store and release a relatively large quantity of heat in a constant narrow temperature range during phase change.
    [Show full text]