TA Section Day/Time. Organic Chemistry FINAL EXAM A (250 points)

Transcription

1 UCSC, Binder ame TA Section Day/Time rganic Chemistry FIAL EXAM A (250 points) D T BEGI TE EXAM TU TE PAGE UTIL ISTUCTED T D S. In the meantime, please read the instructions below. Use your knowledge of organic chemistry conventions to answer the questions in the proper manner. You should be delighted to find that not every topic is included in the exam, otherwise we would be here all day! A representative portion of CEM 109 material is presented to assess your cumulative knowledge of reaction mechanisms, biomolecules, and a bit of medicinal chemistry. Be sure to read each question carefully. Before you start, make sure there are seven exam problems / pages in your exam. You have 2.5 hours to complete this exam. Keep your eyes on your own paper. Electronic devices of any kind are not allowed, including cell phones and calculators. Any student found using any of said devices, or found examining another student s exam, will be promptly removed from the exam room and at minimum will receive a zero on this exam. Such an incident may also be considered a form of academic dishonesty and reported to the UCSC Judiciary Affairs Committee. Close your eyes, take ten slow breaths, and relax until we tell you to start Thanks for a great quarter and good luck to you all!! Page 1 (40) Page 2 (30) Page 3 (30) Page 4 (40) Page 5 (40) Page 6 (35) Page 7 (35) Total

2 CEM 109, FIAL EXAM A Spring Fundamentals/omenclature (a) (15 points) Draw the structures of D-Glucose, β-d-glucopyranose, and pyruvate below. D-Glucose (Fischer) β-d-glucopyranose (aworth) Pyruvate (b) (15 points) Draw the full structures of any three different common amino acids below. Include the name and abbreviations above each structure. ame 3-letter abbreviation 1-letter abbreviation Structure (c) (10 points) DA Base Pairs. edraw nucleobase structures to show the -bonding patterns for the A-T base pair in the space provided. Do not include full nucleotide structures (ribose or phosphate) nucleobases only! 2 Adenine 2 Cytosine Guanine Thymine 2 1

3 CEM 109, FIAL EXAM A Spring Acid-Base Chemistry (a) (10 points) Provide the pka of each compound below and indicate the hybridization of the starred atoms. * * * * * 3 C 2 pka ybridization (*) (b) (8 points) Circle the more basic compound in each pair. (i) (ii) 2 vs. 2 vs. (iii) (iv) vs. vs. (c) (12 points) Draw the dominant ionic forms of L-istidine at the indicated p ranges. Include and circle all formal charges and indicate the net charge of each structure in the boxes below. pka ; pka ; pka 6.10 L-istidine (fully protonated) p < < p < < p < 9.18 p > 9.18 Charge: 2

4 CEM 109, FIAL EXAM A Spring Medicinal Chemistry (a) (15 points) What are the three phases used to describe drug effectiveness in medicinal chemistry? 1. phase = dosage and initial traveling of a drug 2. phase = absorption, distribution, metabolism, elimination 3. phase = binding of drug to receptor (b) (15 points) For each of the compounds below, list the functional groups that contribute to solubility potential. Use this to calculate solubility potential and determine whether each structure as written is likely to be water-soluble. 2 Sulfadiazine antibiotic S 5-Azacytidine chemotherapy agent 2 2 Ampicillin antibiotic S C 2 Compound Functional Groups Solubility Potential (# Carbons per FG) Total Solubility Potential Water-Soluble? (Yes or no) Sulfadiazine 5- Azacytidine Ampicillin Functional Group Solubility Potential Lesser known FG s Alcohol 3-4 carbons 2 Amine / Carboxylic Acid 3 carbons 2 urea Amide 2-3 carbons Ether / Thioether / Urea 2 carbons S Sulfonamide carbons 2 sulfonamide 3

5 CEM 109, FIAL EXAM A Spring Mechanism Warm-up (a) (14 points) During the metabolism of ethanol in humans, alcohol dehydrogenase (AD) degrades ethanol to form acetaldehyde according to the following equation. Add the mechanism arrows to complete this reaction using each of the four components below. is C C Glu-C 2 Add mechanism arrows C 2 AD is Glu-C 2 C 2 (b) (10 points) Add arrows to complete the mechanism. Do not add more intermediates. Add an acid ( ) and base (:B) to complete each step as written. 2 3 (c) (16 points) Complete the mechanism for the synthesis of a C-T dinucleotide below by adding arrows to each step and drawing the product. Use an acid ( ) and/or bases (:B) if needed. You may abbreviate the nucleobases in the product. 2 K to abbreviate nucleobases as "C" and "T" Cytosine - P P Thymine C-T Dinucleotide 4

6 CEM 109, FIAL EXAM A Spring (40 points) Fill in the box (no mechanisms necessary) (a) Penicillin kills bacteria by reacting with a serine residue in the active site of an enzyme responsible for building murein, the polymer that holds bacterial cells together. This nucleophilic acyl substitution reaction occurs to alleviate ring strain in the β-lactam. Draw the product of the reaction between the serine reside in penicillin binding protein (PBP) and isopenicillin. PBP Enzyme S Isopenicillin C 2 - Covalently bound enzyme-isopenicillin (b) The first step in the mavelonate pathway is the Claisen condensation of acetyl CoA. Show the product of that reaction below. 2 SCoA Acetyl CoA SCoA Claisen condensation (c) ne of the final steps in the synthesis of morphine is the reduction of codeinone to codeine. Draw the structure of codeine in the box provided. 3 C Codeinone C 3 ADP ADP Codeine - no abbreviations, have fun! (d) Provide the structure of a triacylglycerol, formed through three esterification reactions between glycerol and three fatty acids. 3 Fatty Acids Glycerol Esterification 3 2 Triacylglycerol 5

7 CEM 109, FIAL EXAM A Spring Amino Acid Biosynthesis The metabolism and catabolism of amino acids involves the co-factor PLP, which requires regeneration for it to be recycled in another process. The overall scheme for PLP regeneration is shown below along with the conversion of pyruvate into alanine. This process is broken down into three steps, outlined below with simplified molecules. 2-3 P 3 Lys 2-3 P 2 3 Pyridoxamine phosphate (PMP) C 2 - Pyruvate (an α-keto acid) Lys PLP-enzyme imine 3 C 2 Alanine (an α-amino acid) In each step, use amino acid residues as acids and bases where appropriate to complete the transformation. Carry out the mechanism in the indicated number of steps. Structures are given in such a way that you do not have to redraw the starting materials. (a) (15 points) Show the mechanism for iminium formation in two steps (one intermediate). 2 C C (b) (5 points) Show the mechanism for isomerization in one step (no intermediate). C 2 C 2 (c) (15 points) Show the mechanism for trans-imination and release of alanine in two steps (one intermediate). 2 Lys C 2 Lys 3 C 2 6

8 CEM 109, FIAL EXAM A Spring Glycolysis The second phase of glycolysis begins with the oxidative phosphorylation of GAP to produce the acyl phosphate in 1,3-bisphosphoglycerate. This process involves covalent binding to the enzyme GAP dehydrogenase and can be broken down into three steps, outlined below with simplified molecules. C C 2 P 2-3 Glyceraldehyde-3-phosphate (GAP) P 4 3- AD AD GAP Dehydrogenase C 2 P 2-3 C 2 P 2-3 1,3-Bisphosphoglycerate Use amino acid residues as acids and bases as needed to complete each transformation. Carry out the mechanism in the indicated number of steps. Structures are given in such a way that you do not have to redraw the starting materials, unless otherwise stated. (a) (8 points) Show the mechanism for the covalent binding of a cysteine residue to an aldehyde in one step (no intermediate). S Cys S-Cys (b) (12 points) Show the mechanism for oxidation of the thiohemiacetal into a thioester using AD in one step (no intermediate). S-Cys Thiohemiacetal C 2 S-Cys Thioester C 2 (c) (15 points) Show the mechanism for conversion of a thioester into an acyl phosphate in two steps (one intermediate). Begin by drawing the Lewis structure of a phosphate ion. S-Cys P 4 3- P 3 2- S Cys Thioester Acyl Phosphate 7

9 CEM 109, FIAL EXAM A Spring 2018 ave a great summer! 8