1. Leukotriene D4 is a cell-signaling molecule widely studied in the context of inflammatory diseases such as asthma and allergy. Supply your responses as requested. H₂N Leuokotriene D4 OH Redraw the structure of Leukotriene D4 in its predominant ionization state in the bloodstream (pH = 7.2). NH 1=0 3 of 8 2. Which of the following compounds can be classified "meso"? None of these compounds are optically active. (Don't forget to consider the eclipsed conformations for D & E!!) MUST HAVE CHIRAL 0 = (A) CENTERS I CH₂ H₁C no chiral Centers ✓ OH (C) CH3 HOH H OH CH₂ A, C.D, E H₂C H H OH H HO CH₂ CH₂ H CH₂ CH₂ (D) (E) по (F) chiral 3. centers Complete the Fisher projection on the right to depict 4-chloro-3-hexanol in the same configuration as indicated in the line and wedge representation below. Also provide the configurations of both chiral centers. Et C H Hwww HO H ce OH H Configuration of C3 Configuration of C4 S S 5 6 Et Total number of chiral centers (or asymmetric centers) in leukotriene D4 4 Total number of stereocenters (or stereogenic centers) in leukotriene D4 4+8=12 Configuration of the asymmetric center marked with an asterisk (*) is R 4. Compare following chair representations to the line and wedge representation of (-)-menthol shown on the right. Identify the one that meets the indicated criterion. Convert the chairs to line & wedge!! بعد علم بعد نعم (A) (B) (D) Z Configuration of the alkene inscribed in the dotted box is Fill in the blanks by identifying the stereochemical relationships: If the configurations of any two chiral centers in leuokotriene D4 are changed, the resulting compound will be a diastereomer of leukotriene D4. If the configurations of ALL chiral centers in leuokotriene D4 are changed, the resulting compound will be enantiomer of leukotriene D4. an 6. Which of the following solvents CANNOT be classified as a polar aprotic solvent. Circle all that apply. Chair conformation (-)-menthol: A Chair conformation of enantiomer of (-)-menthol: B D Chair conformation of a diastereomer of (-)-menthol: Chair conformation of a constitutional isomer of (-)-menthol:, (-)-menthol 5. The following equations describe a two-step sequence known as the Williamson ether synthesis. Complete these equations by supplying curved arrows to indicate the flow of electrons within the reactants of steps 1 & 2. Answer parts (I)-(II) by examining these equations carefully. OH Protic -CEN protic пол- ra-polar Step 1: Indicate TRUE/FALSE by each of the following statements: FALSE Polar aprotic solvents possess both hydrogen-bond donors and acceptors. TRUE Protic solvents possess both hydrogen-bond donors and acceptors. TRUE If solid NaBr was dissolved in a polar aprotic solvent, only the cation (Na') will get solvated, whereas the anion (Br) will remain relatively unsolvated. phenol hydroxide yaroxide anion phenoxide anion Step 2: + H₂O: FALSE The reaction between 1-chlorobutane and sodium iodide will occur at a slower rate when SN2 reactions are phenoxide anion bromoethane ethoxybenzene :Br: bromide anion (1) Step 1 is described as performed in acetone as the solvent vs in methanol as the solvent. 7. Draw the structure of the major product expected in the following reaction. The product stereochemistry must be shown explicitly. accelerated in polar aprotic Solvents. Select the best answer among the following. (a) A Brønsted-Lowry acid-base reaction (c) Both (a) and (b) (b) A Lewis acid-base reaction (d) Neither (a) nor (b) (11) (a)+6 The approximate equilibrium constant (K.) for step 1 is: (Use benchmark pk, values!!) (b)-6 (c) 1/6 (d) 10% (e) 10 Br solvent What is the expected pathway for the above reaction? Provide two observations that support your prediction. Major pathway 1. SN2 Minor pathway. Strong nucleophile, weak base E2 2. A polar aprotic solvent accelerates bimolecular lestitution / elimination pathways. Draw the transition state that leads to the product you've predicted above. Be mindful of partial charges. (111) Identify the following species by writing their names as indicated in the equations above: Electrophile in step 2: bromoethane Nucleophile in step 2: phenoxide anion (IV) Select ALL choices that provide the correct description of step 2. B&D (a) A Brønsted-Lowry acid-base reaction (c) SN1 reaction (b) A Lewis acid-base reaction (d) S2 reaction (VI) In step 2, if the concentration of both reactants is doubled, the overall rate of the reaction will be: (a) doubled (d) will remain unchanged (b) halved (c) quadrupled (4x) [ ·Br = CH3 8. Draw the structure of the alkene expected to be generated in the following reaction. (Hint: Be sure to convert the alkyl halide to meet the requirements of an anti-periplanar transition state.) H₂C-0 H₂C methanol H c. НС H H already anti The configuration of the alkene is N Another alkene is also formed in this reaction. Figur 9. Provide the IUPAC name for the following compound. Be sure to indicate the configurations as necessary. it out (4R, 22)-2-bromo-4-methoxy- Br OCH3 oct-2-en-6- 10. Provide the missing products in each of the following schemes. Be mindful of stereochemical aspects. Some of these reactions involve skeletal rearrangements, which you MUST be able to identify. H-CI H-Br no peroxides HBr NONN LCN ,heat major product Br EtO/Ethanol heat Br Na 11.Provide stepwise curved-arrow mechanisms for transformations (A)-(D). Include all lone pairs and formal charges in your mechanism and be mindful of utilizing correct reaction arrows: Tranformation: (Carbocation rearringement may not always -Br: н aqueous acetone (excess) H₂O: tertiary!! + byproducts + Provide the structures of TS1, TS2 and TS3 as indicates in the following energy profile for the above reaction. TSI TS1: Energy Reactants Substitution product Transformation (B): major product Hint: banana oil 11 TS2 12 مجھے قة Br TS2: TS3 8+ 8+ TS3: H Products Reaction coordinate ..H.... QH₂ OH H3O+ - H₂O Transformation (C): (Your mechanism does not need to justify the role of HgSO4) H3O+ - H₂O catalytic HgSO4 Transformation D: Provide the chain initiation and chain propagation steps. (No fishhooks, no points) コー H-Br RO-OR, light Br