Design Synthesis and SAR of Non-peptidic Urotensin II Agonists
|
|
|
- Gabriel Wilkins
- 5 years ago
- Views:
Transcription
1 MEDICIAL CEMISTY Design Synthesis and SA of on-peptidic Urotensin II Agonists C Val Cys Tyr Lys Trp 2 Glu Thr Pro Asp Cys Phe uman urotensin II (S) pec () pec FL-104 AC-7954 Fredrik Lehmann
2 MEDICIAL CEMISTY Where to start? AC7954 identified as the first non-peptidic Agonist for Urotensin II
3 MEDICIAL CEMISTY The mission: Try to improve the potency and efficacy relative to AC7954 ow? (step 1) different heterocycles different amines various substitution change "spacer" length various substitution
4 etrosynthetic analysis MEDICIAL CEMISTY Li Li Br
5 Synthesis MEDICIAL CEMISTY Br n-buli C 2 S 2 Me % 80-99% Dioxane mw o, 6 min TF, rt % 95-99% + n-buli 10-75%
6 SA (selection) MEDICIAL CEMISTY FL66 Compound pec50 Efficacy AC ± ± 8 FL60 4-F 5.60 ± ± 40 FL47 4-CF ± ± 10 FL52 4-Me 5.01 ± ± 1 FL56 3-Me 5.33 ± ± 51 FL54 2-Me 4.97 ± ± 4 FL ± ± 18 FL ± ± 21
7 Combinations? MEDICIAL CEMISTY 1 2 Compound 1 2 pec50 Efficacy AC ± ± 8 FL97 3,4-Di FL98 6,7-DiMe 2-apthyl FL99 6,7-DiMe 3-Me FL101 6,7-DiMe 3,5-Di-Me Lehmann et al. J Bioorg Med Chem, 2005
8 Small changes can be vital! MEDICIAL CEMISTY AC-7954 pec 50 = 5.95 Inactive!
9 Stereochemistry? MEDICIAL CEMISTY AC (+) 16 pec 50 = 7.11 (-) 16 pec 50 = 5.78
10 Summary of SA MEDICIAL CEMISTY naphthyl tolerated methyl good, phenyl too large not necessery for activity can be exhanged for -alkyl chirality important two carbons most favorable substitution forbidden larger rings tolerated but not smaller dimethyl optimal, larger systems deterimental for activity Ph tolerated, Ph or CCPh too sterically demanding substitution pattern important, but difficult to predict
11 MEDICIAL CEMISTY The mission: Try to improve the potency and efficacy relative to AC7954 ow? (step 2) + pec 50 = 5.95 pec 50 = 5.77
12 MEDICIAL CEMISTY i 1 ii 3v, w iii iv, v vi 2 4a - e vii 2 viii ix 6a - u S 5a - s 8d, e, v 7a - u i) LA, TF, 91%. ii) -C 2 -X, PS-DIPEA, C 2 2, 48 and 78%. iii) -C, EDC, DMAP, C 2 2, 43-98%. iv) C 3 C, 2 S 4. v) 6M (aq), >99%. vi) -C, Et 3, TF, 29-91%. vii) -C, S 2, Et 3, TF, 42-98% or -C, EDC, DMAP, C 2 2, 60-67%. viii) -S 2 -, Et 3, TF, quant. ix) -C, Et 3, TF, 38-98% Lehmann et al. J Med Chem 2006
13 SA (selected) MEDICIAL CEMISTY 3v, w 4a - e 5a - e cmpd pec50 Efficacy n 3v 4-MePh A c 2 3w 2-Me-Ph A c 2 4a 2-MePh 5.77 ± ± b 4-Me-Ph 5.66 ± ± c 4-CF 3 -Ph 5.76 ± ± d 4-Ph-Ph 6.28 ± ± e 2-aphthyl 5.68 ± ± a 2-MePh 5.45 ± ± b 4-Me-Ph 5.87 ± ± c 4-CF 3 -Ph 7.11 ± ± d 4-Ph-Ph 7.11 ± ± 11 2 (-) 5d 4-Ph-Ph 5.84 ± ± 16 5 (+) 5d 4-Ph-Ph 7.49 ± ± e 2-aphthyl 6.39 ± ± 18 2
14 SA (selected) MEDICIAL CEMISTY S 6a - u 7a - u 8d, e, v cmpd pec50 Efficacy n 6a 2-MePh 5.41 ± ± b 4-Me-Ph 5.78 ± ± c 4-CF 3 -Ph 6.60 ± ± d 4-Ph-Ph 6.57 ± ± e 2-aphthyl 6.28 ± ± a 2-MePh 5.64 ± ± b 4-Me-Ph 5.70 ± ± c 4-CF 3 -Ph 6.93 ± ± d 4-Ph-Ph 6.84 ± ± e 2-aphthyl 6.54 ± ± d 4-Ph-Ph A 3 8e 2-aphthyl A 3 8v 4-MePh 5.19 ± ± 10 4
15 r another way MEDICIAL CEMISTY i 2 1 A - C 1-10 {A1 - C10} i) PS-DCC 2 eqv, PS-DMAP 0.2 eqv, C 2 2, rt, 96h, 46-98% Works even in small scale... Cmpd Scale (mg) Yield Purity Scale (mg) Yield Purity {A1} {A7} Lehmann et al. Eur J Med Chem 2007
16 2 2 2 A B C MEDICIAL CEMISTY 1. = 2. = CF 3 3. =Me 4. = 5. = CF 3 6. =Me 7. = 8. = CF 3 9. = Me cmpd A B C 10 Extraction Yield Purity Ion ex Yield Purity Extraction Yield Purity Ion ex Yield Purity Extraction Yield Purity Ion ex Yield Purity
17 2 2 2 A B C MEDICIAL CEMISTY 1. = 2. = CF 3 3. = Me 4. = 5. = CF 3 6. =Me 7. = 8. = CF 3 9. = Me 10 cmpd A B C P EC 50 a Efficacy b P EC 50 a Efficacy b P EC 50 a Efficacy b ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± 5 A c A c ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± ± 14
18 2 2 2 A B C MEDICIAL CEMISTY 1. = 2. = CF 3 3. = Me 4. = 5. = CF 3 6. =Me 7. = 8. = CF 3 9. = Me ,7 120 Efficacy Aliphatic Conjugated pec50 6,2 5,7 A B C 20 5,2 5,7 6,2 6,7 pec50 5, Acid
19 Determination of the absolute configuration MEDICIAL CEMISTY 2 Ph Me (,S) + Ph Me (,) C20 1 C9 C10 C8 C11 C7 2 C6 C1 1 C C14 C13 C12 1 C15 C3 C4 1 C19 C16 C18 C Ph-Ph-C 2 4-Ph-Ph-C C5 2 X-ray structure of the (,)-methoxy phenyl acet amide (S)-FL104 pec ()-FL104 pec
20 MEDICIAL CEMISTY Molecular modelling proposed a pharmacophore for UII-agonists A Å A2 A Å 8.4 Å 4.8 Å 4.8 Å
21 Focus on Mannich reaction App 300 reaction in 2 mmol scale were run in for various time in seven solvents (water, acetic acid, dioxane, TF, DMF, ethanol, and methanol) at three different temperatures. At 150 o C, pressure jumped one bar => release of formaldehyde
22 Focus on Mannich reaction MEDICIAL CEMISTY Table 3. esults from synthesis of Mannich bases using various secondary amines o C, 300s dioxane Product Yield a Product Yield a 19 Diethylamine Thiomorpholine Morpholine Piperidine 61 a) All yields are LC yields given as averages of at least two experiments
23 Focus on Mannich reaction MEDICIAL CEMISTY Lehmann et al, Mol Div 2003
24 Mannich eaction MEDICIAL CEMISTY a) Values for small scale reactions (2 mmol), values within parenthesis refers to large (40 mmol) scale Lehmann et al, Mol Div 2003
25 Mannich eaction Lehmann et al, Mol Div 2003
Solutions In each case, the chirality center has the R configuration
CAPTER 25 669 Solutions 25.1. In each case, the chirality center has the R configuration. C C 2 2 C 3 C(C 3 ) 2 D-Alanine D-Valine 25.2. 2 2 S 2 d) 2 25.3. Pro,, Trp, Tyr, and is, Trp, Tyr, and is Arg,
Structure at the isoelectric point: The predominant form of this tripeptide at ph 1 has a net charge of: (circle one)
ame Key 21 F07-Final exam Page 2 I. (1 points) Using the pka information given on page 12, match the following isoelectric point (pi) values (3.08, 6.00, and 10.76) to their corresponding amino acids by
TMSCl imidazole DMF. Ph Ph OTMS. Michael reaction. Michael reaction Ph R 3. epoxidation O R
eaction using diarylprolinol silyl ether derivatives as catalyst 1) C Et K C 3, ) MgBr, TF TMS hexane, 0 o C TBS p- C 6 4, T C Et 85%, 99% ee Angew. Chem., nt. Ed., 44, 41 (005). rg. Synth., 017, 94, 5.
Conformational Analysis
Conformational Analysis C01 3 C C 3 is the most stable by 0.9 kcal/mole C02 K eq = K 1-1 * K 2 = 0.45-1 * 0.048 = 0.11 C04 The intermediate in the reaction of 2 has an unfavorable syn-pentane interaction,
C H E M I S T R Y N A T I O N A L Q U A L I F Y I N G E X A M I N A T I O N SOLUTIONS GUIDE
C H E M I S T R Y 2 0 0 0 A T I A L Q U A L I F Y I G E X A M I A T I SLUTIS GUIDE Answers are a guide only and do not represent a preferred method of solving problems. Section A 1B, 2A, 3C, 4C, 5D, 6D,
Diastereomeric resolution directed towards chirality. determination focussing on gas-phase energetics of coordinated. sodium dissociation
Supplementary Information Diastereomeric resolution directed towards chirality determination focussing on gas-phase energetics of coordinated sodium dissociation Authors: samu Kanie*, Yuki Shioiri, Koji
O H HO H. !-D-galactopyranose
ame Key W06-Exam o. Page I. ( points) A disaccharide is cleaved by a β-glycosidase, an enzyme that specifically hydrolyzes a β- glycosidic linkage. When the disaccharide is treated with excess dimethyl
Amino Acids and Peptides
Amino Acids Amino Acids and Peptides Amino acid a compound that contains both an amino group and a carboxyl group α-amino acid an amino acid in which the amino group is on the carbon adjacent to the carboxyl
R or S? oxidation #: hybridization:
Remember Lone pair-assisted ionization. ame 15 F07-Exam o. 1 Page I. (0 points) The following compounds are those used in our study on the enzymatic transformation of cholesterol to pregnenolone. 1) Designate
Supporting Information
Supporting Information Novel diphenylmethyl-derived amide protecting group for efficient liquid-phase peptide synthesis; AJIPHASE Daisuke Takahashi*, Tatsuya Yano and Tatsuya Fukui Research Institute For
A. Two of the common amino acids are analyzed. Amino acid X and amino acid Y both have an isoionic point in the range of
Questions with Answers- Amino Acids & Peptides A. Two of the common amino acids are analyzed. Amino acid X and amino acid Y both have an isoionic point in the range of 5.0-6.5 (Questions 1-4) 1. Which
Chapter 4: Amino Acids
Chapter 4: Amino Acids All peptides and polypeptides are polymers of alpha-amino acids. lipid polysaccharide enzyme 1940s 1980s. Lipids membrane 1960s. Polysaccharide Are energy metabolites and many of
Other Methods for Generating Ions 1. MALDI matrix assisted laser desorption ionization MS 2. Spray ionization techniques 3. Fast atom bombardment 4.
Other Methods for Generating Ions 1. MALDI matrix assisted laser desorption ionization MS 2. Spray ionization techniques 3. Fast atom bombardment 4. Field Desorption 5. MS MS techniques Matrix assisted
Aromatic Hydrocarbons
Aromatic Hydrocarbons Aromatic hydrocarbons contain six-membered rings of carbon atoms with alternating single and double carbon-carbon bonds. The ring is sometimes shown with a circle in the center instead
A. B. C. D. 2. Which compound does not give a stable Grignard reagent when reacting with Mg metal?
Practice Test, Chemistry 2220 Final Exam 1. Which structure has the MST signals for its proton NMR? 2. Which compound does not give a stable Grignard reagent when reacting with Mg metal? 3. Which of these
2311A and B Practice Problems to help Prepare for Final from Previous Marder Exams.
2311A and B Practice Problems to help Prepare for Final from Previous Marder Exams. Disclaimer.: Use only to help learn what you need to know and don t expect the final to be in the same form. 1 1. Short
Highlights of Schmidt Reaction in the Last Ten Years
ighlights of Schmidt eaction in the Last Ten Years Dendrobates histrionicus Jack Liu ov. 18, 2003 Introduction Classical Schmidt reaction of aldehydes and carboxylic acids Classical Schmidt reaction of
1G (bottom) with the phase-transition temperatures in C and associated enthalpy changes (in
Supplementary Figure 1. Optical properties of 1 in various solvents. UV/Vis (left axis) and fluorescence spectra (right axis, ex = 420 nm) of 1 in hexane (blue lines), toluene (green lines), THF (yellow
Electronic Supplementary Information
Electronic Supplementary Information A Recyclable Perfluoroalkylated PCP Pincer Palladium Complex Daniel Duncan, Eric G. Hope, Kuldip Singh and Alison M. Stuart* Department of Chemistry, University of
Exam I Answer Key: Summer 2006, Semester C
1. Which of the following tripeptides would migrate most rapidly towards the negative electrode if electrophoresis is carried out at ph 3.0? a. gly-gly-gly b. glu-glu-asp c. lys-glu-lys d. val-asn-lys
A Plausible Model Correlates Prebiotic Peptide Synthesis with. Primordial Genetic Code
Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2018 A Plausible Model Correlates Prebiotic Peptide Synthesis with Primordial Genetic Code Jianxi Ying,
Chiral Brønsted Acid Catalysis
Chiral Brønsted Acid Catalysis Aryl Aryl Aryl Aryl S CF 3 2 P Fe CF 3 CF 3 2 Jack Liu ov. 16, 2004 CF 3 Introduction Chiral Brønsted acid catalysis in nature: enzymes and peptides Chiral Brønsted acid
What makes a good graphene-binding peptide? Adsorption of amino acids and peptides at aqueous graphene interfaces: Electronic Supplementary
Electronic Supplementary Material (ESI) for Journal of Materials Chemistry B. This journal is The Royal Society of Chemistry 21 What makes a good graphene-binding peptide? Adsorption of amino acids and
Development of Small Organic Molecules as Catalysts for Asymmetric
Development of Small Organic Molecules as Catalysts for Asymmetric Organic Transformations The development of new and efficient catalysts capable of catalyzing enantioselective transformation in a controlled
Hour Examination # 3
CHEM 343 Principles of Organic Chemistry II Summer 2014 Exam # 3 Solutions Key Page 1 of 8 CHEM 343 Principles of Organic Chemistry II Summer 2014 Instructor: Paul J. Bracher Hour Examination # 3 Tuesday,
Supporting Information
Supporting Information Cobalt(II)-Catalyzed Acyloxylation of C- Bonds in Aromatic Amides with Carboxylic Acids Rina Ueno, Satoko atsui, and aoto Chatani* Department of Applied Chemistry, Faculty of Engineering,
Sequential resonance assignments in (small) proteins: homonuclear method 2º structure determination
Lecture 9 M230 Feigon Sequential resonance assignments in (small) proteins: homonuclear method 2º structure determination Reading resources v Roberts NMR of Macromolecules, Chap 4 by Christina Redfield
Proteins: Characteristics and Properties of Amino Acids
SBI4U:Biochemistry Macromolecules Eachaminoacidhasatleastoneamineandoneacidfunctionalgroupasthe nameimplies.thedifferentpropertiesresultfromvariationsinthestructuresof differentrgroups.thergroupisoftenreferredtoastheaminoacidsidechain.
Downloaded from:
Withers-Martinez, C; Suarez, C; Fulle, S; Kher, S; Penzo, M; Ebejer, JP; Koussis, K; ackett, F; Jirgensons, A; Finn, P; Blackman, MJ (2012) Plasmodium subtilisin-like protease 1 (SUB1): insights into the
Aldehydes and Ketones
Aldehydes and Ketones Preparation of Aldehydes xidation of Primary Alcohols --- 2 P 1o alcohol ydroboration of a Terminal Alkyne, followed by Tautomerization --- 1. B 3, TF 2. 2 2, K 2 terminal alkyne
1. Draw the structure of oxazolone formed upon activation of N-Acetylvaline
Peptide quiz 1 (5 questions for 10 minutes) 10 points max 1. Draw the structure of oxazolone formed upon activation of -Acetylvaline 3 C 3 C 2. The following DKP (1) is prepared by cyclisation of dipeptide
Answer Key Evening Exam 2v1
Page 1 of 11 Evening Exam 2 ame: Chem 250 Answer Key Evening Exam 2v1 This exam is composed of 40 questions. As discussed in the course syllabus, honesty and integrity are absolute essentials for this
Affects pk a? Derivatization to Amides. Identify unknown. carboxylic acid
sodium salt of unknown aromatic + soluble impurities + insoluble impurities total insoluble impurities dissolve in water, filter aq. sol n of unk. sodium salt + sol. impurities account for all masses;
Department of Chemistry, Colorado State University, Fort Collins, Colorado University of Colorado Cancer Center, Aurora, Colorado 80045
Improved Biomimetic Total Synthesis of d,l-stephacidin A Thomas J. Greshock 1 and Robert M. Williams 1,2 * 1 Department of Chemistry, Colorado State University, Fort Collins, Colorado 80523 2 University
Chem 316/422 Beauchamp 1 Match the step number in the synthesis with the letter of the reagents listed just below.
hem 316/422 Beauchamp 1 Match the step number in the synthesis with the letter of the reagents listed just below. TP l Et step 8 4 5 eagents used in synthesis A B D E F a DMF (solvent) 1. (i-pr) 2 Li (LDA)/TF
Supporting Information
Electronic Supplementary Material (ESI) for New Journal of Chemistry. This journal is The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2018 Supporting Information Efficient
Section Week 3. Junaid Malek, M.D.
Section Week 3 Junaid Malek, M.D. Biological Polymers DA 4 monomers (building blocks), limited structure (double-helix) RA 4 monomers, greater flexibility, multiple structures Proteins 20 Amino Acids,
FIVE MEMBERED AROMATIC HETEROCYCLES
FIVE MEMBERED AROMATIC HETEROCYCLES 63 Electrophilic aromatic substitution reaction of five membered aromatic heterocycles X = O, S or NH a-substitution b-substitution The Substitution is regioselective
Copper-Catalyzed Synthesis of Esters from Ketones. Alkyl Group as a Leaving Group.
Copper-Catalyzed Synthesis of Esters from Ketones. Alkyl Group as a Leaving Group. akatani, Y.; Koizumi, Y.; Yamasaki, R.; Saito, S. rg. Lett. 2008, 10, 2067-2070. An Annulation Reaction for the Synthesis
Practice Synthetic Problems: CHEM 235 Page 2
Practice Synthetic Problems: CM 235 Page 2 Syntheses based on diethyl malonate, ethyl acetoacetate, etc. Using diethyl malonate and any other necessary organic reagents, show a synthesis of: a) 2,2-dimethyl-1,3-propanediamine
NH 2. Biochemistry I, Fall Term Sept 9, Lecture 5: Amino Acids & Peptides Assigned reading in Campbell: Chapter
Biochemistry I, Fall Term Sept 9, 2005 Lecture 5: Amino Acids & Peptides Assigned reading in Campbell: Chapter 3.1-3.4. Key Terms: ptical Activity, Chirality Peptide bond Condensation reaction ydrolysis
water methanol dimethyl ether Ether can only act as a hydrogen bond acceptor H-bond acceptor O R
Chapter 14: Ethers and Epoxides; Thiols and Sulfides 14.1 Introduction to Ethers An ether group is an oxygen atom that is bonded to two carbons. The ether carbons can be part of alkyl, aryl, or vinyl groups.
CHEM 203. Final Exam December 15, 2010 ANSWERS. This a closed-notes, closed-book exam. You may use your set of molecular models
CEM 203 Final Exam December 15, 2010 Your name: ANSWERS This a closed-notes, closed-book exam You may use your set of molecular models This test contains 15 pages Time: 2h 30 min 1. / 16 2. / 15 3. / 24
MEDICINAL CHEMISTRY I EXAM #1
MEDICIAL CEMISTRY I EXAM #1 1 September 30, 2005 ame SECTI A. Answer each question in this section by writing the letter corresponding to the best answer on the line provided (2 points each; 50 points
Electronic Supplementary Information
Electronic Supplementary Information 1. Reagents All the L-amino acids and L-glutathione (reduced form) were purchased from Sangon Biotch. o. (Shanghai, hina); Methyl orange, potassium tetrachloropalladate(ii),
Synthesis of Peptide-Grafted Comb Polypeptides via Polymerisation of NCA-Peptides
Supporting Information to Synthesis of Peptide-Grafted Comb Polypeptides via Polymerisation of NCA-Peptides Hiroshi Enomoto, Benjamin Nottelet, Soultan Al Halifa, Christine Enjalbal, Mathieu Dupré, Julien
CHMI 2227 EL. Biochemistry I. Test January Prof : Eric R. Gauthier, Ph.D.
CHMI 2227 EL Biochemistry I Test 1 26 January 2007 Prof : Eric R. Gauthier, Ph.D. Guidelines: 1) Duration: 55 min 2) 14 questions, on 7 pages. For 70 marks (5 marks per question). Worth 15 % of the final
B O C 4 H 2 O O. NOTE: The reaction proceeds with a carbonium ion stabilized on the C 1 of sugar A.
hbcse 33 rd International Page 101 hemistry lympiad Preparatory 05/02/01 Problems d. In the hydrolysis of the glycosidic bond, the glycosidic bridge oxygen goes with 4 of the sugar B. n cleavage, 18 from
Total Synthesis of Saxitoxin
Total ynthesis of axitoxin 2 2 2 John Baird April 11, 2006 1 First isolated in 1957 by chantz et al Isolation and Properties X-Ray tructure obtained in 1975 Freely soluble in water and methanol ptical
Peptide Syntheses. Illustrative Protection: BOC/ t Bu. A. Introduction. do not acid
Kevin Burgess, May 3, 2017 1 Peptide yntheses from chapter(s) in the recommended text A. Introduction do not acid -Met-e- -Met-Met- -e-e- -e-met- dipeptide dipeptide dipeptide dipeptide diketopiperazine
Rapid Access to Compound Libraries through Flow Technology: Fully Automated Synthesis of a 3-Aminoindolizine Library via Orthogonal Diversification
Rapid Access to Compound Libraries through Flow Technology: Fully Automated Synthesis of a 3-Aminoindolizine Library via rthogonal Diversification Paul P. Lange and Keith James* Department of Chemistry,
Compound Number. Synthetic Procedure
Compound Number 1 2 3 4 5 Synthetic Procedure Compound 1, KY1220, (Z)-5-((1-(4-nitrophenyl)-1H-pyrrol-2-yl)methylene)-2-thioxoimidazolidin-4-one was purchased from Chemdiv, Catalog #3229-2677, 97% HPLC
Heterocyclic Chemistry - Midterm. May 6 th, Professor Baran Department of Chemistry The Scripps Research Institute
eterocyclic Chemistry - Midterm May 6 th, 2008 Professor Baran Department of Chemistry The cripps Research Institute ame: Last 4 digits of your ocial ecurity #: This is an open-notes exam designed to last
Ramachandran Plot. 4ysz Phi (degrees) Plot statistics
B Ramachandran Plot ~b b 135 b ~b ~l l Psi (degrees) 5-5 a A ~a L - -135 SER HIS (F) 59 (G) SER (B) ~b b LYS ASP ASP 315 13 13 (A) (F) (B) LYS ALA ALA 315 173 (E) 173 (E)(A) ~p p ~b - -135 - -5 5 135 (degrees)
Chem 250 Evening Exam 2
Page 1 of 10 Evening Exam 2 ame:: Chem 250 Evening Exam 2 This exam is composed of 40 questions. As discussed in the course syllabus, honesty and integrity are absolute essentials for this class. In fairness
PROCESS FOR THE PREPARATION OF 5-CYANOPHTHALIDE AND INTERMEDIATES USEFUL THEREIN.
ABSTRACT: PRCESS FR THE PREPARATIN F 5-CYANPHTHALIDE AND INTERMEDIATES USEFUL THEREIN. Process for the preparation of 5-cyanophthalide is disclosed which comprises reacting a pharmaceutically acceptable
Supporting Information
1 Supporting Information Gold-catalyzed Synthesis of 3-arylindoles via Annulation of Nitrosoarenes and Alkynes Siva Murru, August A. Gallo and Radhey S. Srivastava* Department of Chemistry, University
Read more about Pauling and more scientists at: Profiles in Science, The National Library of Medicine, profiles.nlm.nih.gov
2018 Biochemistry 110 California Institute of Technology Lecture 2: Principles of Protein Structure Linus Pauling (1901-1994) began his studies at Caltech in 1922 and was directed by Arthur Amos oyes to
Supporting Information
Supporting Information A General thod for Two-Step Transamidation of Secondary Amides using Commercially Available, Airand Moisture-Stable Palladium/C (-eterocyclic Carbene) Complexes Guangrong ng, Peng
Supporting Text Synthesis of (2 S ,3 S )-2,3-bis(3-bromophenoxy)butane (3). Synthesis of (2 S ,3 S
Supporting Text Synthesis of (2S,3S)-2,3-bis(3-bromophenoxy)butane (3). Under N 2 atmosphere and at room temperature, a mixture of 3-bromophenol (0.746 g, 4.3 mmol) and Cs 2 C 3 (2.81 g, 8.6 mmol) in DMS
OH OH OH CH 2 CH 2 C(CH 3 ) 2 (a) CH 3 CHCH 2 CHCH(CH 3 ) 2. (b)
hem 226 Problem Set #8 Fundamentals of rganic hemistry, 4 th edition, John McMurry. hapter 8 1. Give IUPA names for the following alcohols. 2 2 ( 3 ) 2 3 2 ( 3 ) 2 Longest chain = 6 carbons:...hexanediol.
Chapter 18: Carbonyl Compounds II
Chapter 18: Carbonyl Compounds II Learning bjectives: 1. ecognize and assign names to aldehydes and ketones. 2. Write the mechanism for nucleophilic addition and nucleophilic addition-elimination reactions
Heterocyclic Chemistry Midterm Examination. 3 May Professor Baran Department of Chemistry The Scripps Research Institute
eterocyclic Chemistry Midterm Examination 3 May 2013 Professor Baran Department of Chemistry The cripps Research Institute ame: Last 4 digits of your ocial ecurity #: This is a 2-hour test that you have
Central Dogma. modifications genome transcriptome proteome
entral Dogma DA ma protein post-translational modifications genome transcriptome proteome 83 ierarchy of Protein Structure 20 Amino Acids There are 20 n possible sequences for a protein of n residues!
"-Amino Acids: Function and Synthesis
"-Amino Acids: Function and Synthesis # Conformations of "-Peptides # Biological Significance # Asymmetric Synthesis Sean Brown MacMillan Group eting ovember 14, 2001 Lead eferences: Cheng,. P.; Gellman,
Ligand-receptor interactions
University of Silesia, Katowice, Poland 11 22 March 2013 Ligand-receptor interactions Dr. Pavel Polishchuk A.V. Bogatsky Physico-Chemical Institute of National Academy of Sciences of Ukraine Odessa, Ukraine
ALCOHOLS: Properties & Preparation
ALLS: Properties & Preparation General formula: -, where is alkyl or substitued alkyl. Ar-: phenol - different properties. Nomenclature 1. ommon names: Name of alkyl group, followed by word alcohol. 2.
PART-I Development of New Synthetic Methodologies Using Heterogeneous Catalysts or Polyethylene Glycol
PAT-I Development of New Synthetic Methodologies Using eterogeneous Catalysts or Polyethylene Glycol Chapter 1.1.1 eterogeneous catalysts in organic synthesis: Introduction There have been a number of
Chapter 17: Carbonyl Compounds II
Chapter 17: Carbonyl Compounds II Learning bjectives: 1. ecognize and assign names to aldehydes and ketones. 2. Write the mechanism for nucleophilic addition and nucleophilic addition-elimination reactions
Catalytic Reductive Dehydration of Tertiary Amides to Enamines under Hydrosilylation Conditions
SUPPORTIG IFORMATIO Catalytic Reductive Dehydration of Tertiary Amides to Enamines under Hydrosilylation Conditions Alexey Volkov, a Fredrik Tinnis, a and Hans Adolfsson.* a a Department of Organic Chemistry,
Department of Chemistry SUNY/Oneonta. Chem Organic Chemistry II Examination #4 - May 5, 2003 ANSWERS
Department of hemistry SUY/neonta hem 322 - rganic hemistry II Examination #4 - May 5, 2003 ASWERS ISTRUTIS This examination is in multiple choice format and the answers should be placed on the "Test Scoring
Packing of Secondary Structures
7.88 Lecture Notes - 4 7.24/7.88J/5.48J The Protein Folding and Human Disease Professor Gossard Retrieving, Viewing Protein Structures from the Protein Data Base Helix helix packing Packing of Secondary
Enantioselective Organocatalytic Michael Addition of Malonate Esters to Nitro Olefins Using Bifunctional Cinchonine Derivatives
Enantioselective rganocatalytic Michael Addition of Malonate Esters to itro lefins Using Bifunctional Cinchonine Derivatives Jinxing Ye, Darren J. Dixon * and Peter S. Hynes School of Chemistry, University
1-What is substitution reaction? 2-What are can Nucleophilic Substitution Reaction? 3- SN1 reaction. 4-SN2 reaction 5- mechanisms of SN1&SN2
1-What is substitution reaction? 2-What are can Nucleophilic Substitution eaction? 3- SN1 reaction. 4-SN2 reaction 5- mechanisms of SN1&SN2 1- SUBSTITUTION EACTIONS 1-Substitution eaction In this type
NMR study of complexes between low molecular mass inhibitors and the West Nile virus NS2B-NS3 protease
University of Wollongong Research Online Faculty of Science - Papers (Archive) Faculty of Science, Medicine and Health 2009 NMR study of complexes between low molecular mass inhibitors and the West Nile
Chiral Bronsted Acids as Catalysts
Chiral Bronsted Acids as Catalysts Short Literature Seminar 6/3/08 Dustin aup BIL Derived osphoric Acids - First reported in 1992 as a ligand by irrung and coworkers. 4 h 2 irrung Tet. Lett. 1992, 33,
Supplementary Figure 3 a. Structural comparison between the two determined structures for the IL 23:MA12 complex. The overall RMSD between the two
Supplementary Figure 1. Biopanningg and clone enrichment of Alphabody binders against human IL 23. Positive clones in i phage ELISA with optical density (OD) 3 times higher than background are shown for
CHEM J-8 June Complete the following table. Make sure you give the name of the starting material where indicated. REAGENTS/ CONDITIONS
CEM1102 2014-J-8 June 2014 Complete the following table. Make sure you give the name of the starting material where indicated. STARTIG MATERIAL REAGETS/ CDITIS STRUCTURAL FRMULA(S) F MAJR RGAIC PRDUCT(S)
Preparation of Alkyl Halides, R-X. Reaction of alkanes with Cl 2 & Br 2 (F 2 is too reactive, I 2 is unreactive): R + X X 2.
Preparation of Alkyl alides, R-X Reaction of alkanes with Cl 2 & Br 2 (F 2 is too reactive, I 2 is unreactive): UV R + X 2 R X or heat + X This mechanism involves a free radical chain reaction. A chain
Q.1 Draw structures for all amines of molecular formula C 4 H 11 N. Classify them as primary, secondary or tertiary amines.
1 AMIES Structure ontain the 2 group. lassification primary (1 ) amines secondary (2 ) amines tertiary (3 ) amines quarternary (4 ) ammonium salts + 1 2 3 4 Aliphatic Aromatic methylamine, ethylamine,
Principles of Biochemistry
Principles of Biochemistry Fourth Edition Donald Voet Judith G. Voet Charlotte W. Pratt Chapter 4 Amino Acids: The Building Blocks of proteins (Page 76-90) Chapter Contents 1- Amino acids Structure: 2-
Loudon Chapter 19 Review: Aldehydes and Ketones CHEM 3331, Jacquie Richardson, Fall Page 1
Loudon Chapter 19 eview: Aldehydes and Ketones CEM 3331, Jacquie ichardson, Fall 2010 - Page 1 Beginning with this chapter, we re looking at a very important functional group: the carbonyl. We ve seen
CHEM J-9 June 2014
CEM1611 2014-J-9 June 2014 Alanine (ala) and lysine (lys) are two amino acids with the structures given below as Fischer projections. The pk a values of the conjugate acid forms of the different functional
Hour Examination # 3
CHEM 343 Principles of Organic Chemistry II Summer 2014 Exam # 3 Problem Booklet Page 1 of 8 CHEM 343 Principles of Organic Chemistry II Summer 2014 Instructor: Paul J. Bracher Hour Examination # 3 Tuesday,
7.012 Problem Set 1. i) What are two main differences between prokaryotic cells and eukaryotic cells?
ame 7.01 Problem Set 1 Section Question 1 a) What are the four major types of biological molecules discussed in lecture? Give one important function of each type of biological molecule in the cell? b)
Secondary Structure. Bioch/BIMS 503 Lecture 2. Structure and Function of Proteins. Further Reading. Φ, Ψ angles alone determine protein structure
Bioch/BIMS 503 Lecture 2 Structure and Function of Proteins August 28, 2008 Robert Nakamoto rkn3c@virginia.edu 2-0279 Secondary Structure Φ Ψ angles determine protein structure Φ Ψ angles are restricted
-1- HO H O H. β-d-galactopyranose (A) OMe CH 3 I. MeO. Ag 2 O. O Me HNO 3. OAc (CH 3 CO) 2 O. AcO. pyridine. O Ac. NaBH 4 H 2 O. MeOH. dry HCl.
-1-1. Draw structures for the products you would expect to obtain from reaction of β-dgalactopyranose () with each of the reagents below. Be sure to include all relevant stereochemistry. (40 pts). β-d-galactopyranose
Chapter 5. Nucleophilic aliphatic substitution mechanism. by G.DEEPA
Chapter 5 Nucleophilic aliphatic substitution mechanism by G.DEEPA 1 Introduction The polarity of a carbon halogen bond leads to the carbon having a partial positive charge In alkyl halides this polarity
Nickel-Catalyzed Reductive Cross-Electrophile-Coupling Between Aryl and Alkyl Halides
ickel-catalyzed Reductive Cross-Electrophile-Coupling Between Aryl and Alkyl Halides Eunjae Shim Zakarian Group Literature Talk / Dec 13 th, 2018 University of California, Santa Barbara Table of Contents
C C H 2. O p-tsoh (catalytic) H 3 O +! O
ame Key 15 W06-Exam o. Page I. ( points) Pheromones are those chemicals that play a role in communication between individual animals or insects. Structure 1 is the pheromone of the Japanese peach moth
Novel Water-Soluble Near-Infrared Cyanine Dyes: Synthesis, Spectral Properties, and Use in the Preparation of Internally Quenched Fluorescent Probes
ovel Water-Soluble ear-infrared Cyanine Dyes: Synthesis, Spectral Properties, and Use in the Preparation of Internally Quenched Fluorescent Probes Cédric Bouteiller,,, Guillaume Clavé,,, Aude Bernardin,,
Unraveling the degradation of artificial amide bonds in Nylon oligomer hydrolase: From induced-fit to acylation processes
Electronic Supplementary Material (ESI) for Physical Chemistry Chemical Physics. This journal is the Owner Societies 2015 Supporting Information for Unraveling the degradation of artificial amide bonds
Biological Macromolecules
Introduction for Chem 493 Chemistry of Biological Macromolecules Dr. L. Luyt January 2008 Dr. L. Luyt Chem 493-2008 1 Biological macromolecules are the molecules of life allow for organization serve a
20.3 Alkylation of Enolate Anions
864 APTER 20 ELATE AD TER ARB ULEPILES which precipitates as a yellow solid, provides a positive test for the presence of a methyl ketone The reaction can also be used in synthesis to convert a methyl
CHEM1907/ J-7 June 2003 B CHO. Give the products obtained when D-xylose is treated with the following reagents. [Ag(NH 3 ) 2 ] + / OH solution
![CHEM1907/ J-7 June 2003 B CHO. Give the products obtained when D-xylose is treated with the following reagents. [Ag(NH 3 ) 2 ] + / OH solution](/thumbs/74/70798789.jpg "CHEM1907/ J-7 June 2003 B CHO. Give the products obtained when D-xylose is treated with the following reagents. [Ag(NH 3 ) 2 ] + / OH solution")
EM1907/8 2003-J-7 June 2003 onsider the following two monosaccharides, (A) and (B). 8 2 (A) 2 (B) -D-altropyranose -D-xylofuranose Draw Fischer projections of the open chain forms of A and B. A B 2 2 Give
an axial "X" is necessary for a succesful E2 reaction and also works better for S N 2
cleophilic Substitution & Elimination hemistry 1 Templates for predicting S2 and E2 reactions primary - β α α β two different perspectives secondary - β β α β β α two different perspectives tertiary -
Supplementary Figure 1. Primary protein sequence alignment of engineered AcEZH2_ X,
Supplementary Figure 1. Primary protein sequence alignment of engineered AcEZH2_ X, HsEZH2 (Q15910) and AcEZH2 (G1KPH4) 1. Sequence alignment was performed using BLAST. A c t i v i t y ( n o r m a l i
Supplementary Information
Supplementary Information Click and Photo-unclick Chemistry of Aminoacrylate for Visible Light-triggered Drug Release Moses Bio, a, b Gregory Nkepang, a, b Youngjae You a, b, * a Department of Pharmaceutical
Properties of amino acids in proteins
Properties of amino acids in proteins one of the primary roles of DNA (but not the only one!) is to code for proteins A typical bacterium builds thousands types of proteins, all from ~20 amino acids repeated
Mechanism Problem. 1. NaH allyl bromide, THF N H
Mechanism Problem 1. a allyl bromide, TF 2. 9-BB (1.2 equiv), TF, rt; ame (1.2 equiv); t-buli (2.4 equiv), TMEDA (2.4 equiv) 30 to rt; allyl bromide; 30% 2 2, aq. a, 0 C (58% yield) Mechanism Problem 9-BB