Organic Chemistry FINAL EXAM A (250 points)

Transcription

1 UCSC, Binder ame Student ID # Section Day/Time rganic Chemistry FIAL EXAM A (250 points) D T BEGI TE EXAM R TUR TE PAGE UTIL ISTRUCTED T D S. In the meantime, please read the instructions below. In each of the following problems, use your knowledge of organic chemistry conventions to answer the questions in the proper manner. Be sure to read each question carefully. You have two hours to complete this exam. Point distributions are given throughout the exam so you can use your time wisely. You may choose to skip either page 7, 8, or 9 without penalty. If you do all three pages, one page (lowest score) will be extra credit (10 points max). 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. Grader use only Page 2 (40) Page 3 (40) Page 4 (40) Page 5 (30) Page 6 (40) Page 7 (30) Page 8 (30) Page 9 (30) Total

2 CEM 109, FIAL EXAM A Spring

3 CEM 109, FIAL EXAM A Spring 2015 (40 points) Page 2 Aromaticity & Basicity (a) (15 points) Circle all of the basic nitrogens on the compounds below. For each compound, put a star (*) next to the that you would predict to be the most basic. int: the pka of the conjugate acid of pyridine is significantly lower than that of alkyl amines. F icotine Risperidinone (b) (10 points) Circle the compounds that are aromatic. 2 (c) (15 points) The pka of purine (8.9) is significantly lower than most amines such as diethylamine. Indicate the approximate pka of diethylamine, draw the conjugate base of each, and briefly explain the difference in acidity. Purine Diethylamine pka 2

4 CEM 109, FIAL EXAM A Spring 2015 (40 points) Page 3 ucleic Acids (a) (10 points) Consider the structures of the nucleobases below. Indicate each atom that has the potential to serve as an -bond donor (d) or -bond acceptor (a). 2 Adenine Guanine 2 R 2 Cytosine Thymine, R = C 3 Uracil, R = (b) (15 points) Draw the nucleoside of adenine and nucleotide of thymine as DA monomers. (c) (15 points) Draw the A-T dinucleotide in DA form. You may abbreviate the nucleobase portions of the structure as A and T. 3

5 CEM 109, FIAL EXAM A Spring 2015 (40 points) Page 4 Medicinal Chemistry (a) (10 points) Indicate whether cephalexin and penicillin G are more likely to be absorbed through the membranes in stomach lining (p 2) or intenstinal walls (p 8). The structures provided are in the physiological state (p 7.4). Circle one: Stomach Intestines 3 + S Cephalexin (a cephalosporin) S Penicillin G C 2 - Circle one: Stomach Intestines (b) (10 points) Identify the pharmacophore in the following antiviral agents. 2 Pharmacophore 2 Famciclovir Vidarabine 2 Ganciclovir 2 Acyclovir (c) (20 points) Penicillins and cephalosporins are part of the β-lactam antibiotics family. The mode of action is an irreversible (covalent) bond that forms when a serine residue in the active site of bacterial transpeptidase opens the β-lactam. Given the structure of penicillin G below and the abbreviated form of the active site residue (PBP--C 2 ), propose a reasonable mechanism for the deactivation of bacterial transpeptidase (penicillin-binding protein, PBP). Be sure to draw the product of the penicillin-pbp adduct. S Penicillin G C 2-4

6 CEM 109, FIAL EXAM A Spring 2015 (30 points) Page 5- Medicinal Chemistry - Absorption Table 1. Solubility Potential Functional Group Solubility Potential (in a polyfunctional molecule) Alcohol 3-4 carbons Phenol 3-4 carbons Amine 3 carbons Carboxylic acid 3 carbons Ester 3 carbons Amide 2-3 carbons Ether 2 carbons Aldehyde 2 carbons Ketone 2 carbons Urea 2 carbons Charged groups (+: ammonium salts; - : carboxylates, phenolates, sulfates; - : carbons sulfonamides) (a) (19 points) Use the solubility potential table to determine whether xycodone and Iriomoteolide- 1a are water-soluble. If the compound(s) is/are not soluble, suggest a simple way to increase its absorption. C 3 xycodone Iriomoteolide-1a (b) (11 points) Explain why/how Valium can be soluble in the extracellular fluid and the cytoplasm (aqueous conditions), but still passes through the non-polar cell membrane. Cl Diazepam (Valium) 5

7 CEM 109, FIAL EXAM A Spring 2015 (40 points) Page 6 Drug (Bio)synthesis (a) (20 points) Amoxicillin, a common antibiotic, is biosynthesized from three amino acids. (1) Circle the three portions of the molecule that are derived from the three amino acids. ame these amino acids for extra credit. (2) Connect those three amino acids to draw a tripeptide between those three amino acids. 3 + S Amoxicillin C 2 - (c) (10 points) Make some heroine (just on paper, don t do drugs)! Given the structure of morphine, show its reaction with an excess of acetic anhydride and draw the structure of heroine (no mechanism). Acetic Anhydride (excess) Morphine eroin 6

8 CEM 109, FIAL EXAM A Spring 2015 (30 points) Page 7 Morphine Biosynthesis The first cyclization reaction in the biosynthesis of morphine involves the coupling of tyrosine derivatives dopamine and p-hydroxyphenylacetaldehyde. These two react to form an iminium intermediate. Subsequent electrophilic aromatic substitution facilitates cyclization, producing (S)- orcoclaurine. Use the materials below along with appropriate amino acid residues as acids and bases to show the full arrow-pushing mechanism of the formation of the product below within the enzyme active site. Be sure to show the intermediates after each step in the spaces below. Redraw the components please do not draw any arrows to or from the structures provided! (a) (15 points) C (S)-orcoclaurine synthase + 2 Dopamine p-ydroxyphenyl acetaldehyde (b) (15 points) + (S)-orcoclaurine synthase (S)-orcoclaurine 7

9 CEM 109, FIAL EXAM A Spring 2015 (30 points) Page 8 Lipid Biosynthesis Are you seeing the patterns yet? In CEM 109, we observed Claisen condensation reactions in several metabolic processes, including lipid biosynthesis and polyketide synthesis. Read the description of the process below and use your knowledge of metabolic processes to draw the product after each step. Use the materials below along with amino acid residues as acids and bases to show the full arrow-pushing mechanisms of the processes below. Amino acids should be brought in as their natural physiological state and recycled through the pathway. Redraw the components please do not draw any arrows to or from the structures provided! The first step in the mevalonate biosynthesis is a Claisen condensation to yield acetoacetyl CoA: (1) The acetyl group is first bound to the enzyme by a nucleophilic acyl substitution reaction with a cysteine thiol group. (2) Formation of an enolate ion from a second molecule of Acetyl CoA is followed by Claisen condensation to yield the product. SCoA Acetyl CoA Cys--S + SCoA Acetyl CoA 1 SCoA Covalent Binding to Enzyme Enzyme-Bound Intermediate 2 Cys--S Claisen Condensation & Release from Enzyme Acetoacetyl CoA 8

10 CEM 109, FIAL EXAM A Spring 2015 ave a great summer! 9