-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.

Transcription

1 -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 () a) 3 I g 2 b) c) ( 3 ) 2 pyridine c c c c c d) ab e) dry l

2 -2- f) 1) 2) DIB 3) g) Br h) 2 2) ( 3 ) 2 3) a 2 i) red / I (n-hexane) 2. The octapeptide saralasin is a specific antagonist of agniotensin II. derivative of saralasin is used therapeutically as an antihypertensive. mino acid analysis of saralasin shows the presence of the following amino acids : la, rg, is, ro, ar, Tyr, 2 Val. a) Briefly describe a plausible technique for analyzing the amino acid content of saralasin. Two-three sentences plus a diagram will suffice. (10 pts). 3 Rigorous hydrolysis of a protein with aqueous l will cleave all peptide bonds to liberate the component amino acids. nalyze the amino acids by chromatography, where the retention time is characteristic of each, and the absorbance of a suitable derivative is proportional to molar quantity. absorbance retention time

3 -3- b) -terminal analysis by the Edman method shows that saralasin contains sarcosine (-methyl aminoethanoic acid) at the -terminus (see below). rovide structures for and D, and a detailed mechanism for this cleavage. (15 pts). B B 1) -== / + / peptide 2 + D 2) 3 + nucleophilic addition peptide 2 + catalyzed cyclization peptide 2 2 (peptide) 2 + catalyzed cleavage B peptide 2 + catalyzed rearrangement D c) artial hydrolysis of saralasin with dilute l yields the following fragments: Tyr-Val-is, ar-rg-val, is-ro-la, Val-Tyr-Val, rg-val-tyr. What is the structure of saralasin? (10 pts). ar-rg-val rg-val-tyr Val-Tyr-Val Tyr-Val-is is-ro-la The omplete equence is: ar-rg-val-tyr-val-is-ro-la

4 -4- d) ropose a solid state synthesis of the fragment Tyr-Val-is beginning with polymer (see below), and utilizing any protected derivatives of Try, Val and is of your chosing. how all reagents and steps clearly. (15 pts). 2 l - B Tyr Val 2 is TF B B D B 2 TF 2 2 D 2 B B 2 1) TF 2) 2 / d Tyr-Val-is 3. For each reaction given below, provide either the missing reagents or products (in the boxes). how any intermediates in the space provided. For multistep syntheses, be sure to list the reagents in the order they are utilized (none require more than 3 steps). (40 pts). a) Et a 3 + Et Et

5 -5- b) l 1) 3 2) Br 2 / ) 2 2 / d c) eq Br Br d) 1) R 3 2) - 3) c 2 e) Et 1) 1 equiv LD 2) I Et f) -( 2 ) 5-1) - 2) 2 Et / 2 / d 3) excess l l 2 Et

6 -6- excess g) Br ) KMn 4 / h) 2) (- 2 ) 3) 4. rovide a detailed mechanistic rationale for the transformation shown below. (15 pts) T

7 -7-5. If the D sequence -T-G-GT- were incorrectly copied during replication and became -TG-G-GT-, what effect would there be on the sequence of the protein produced during translation (use the data from the table below). (15 pts). odon ssignments 1st base (5 end) 2nd base Third base (3 end) U G U U e e Leu Leu er er er er Tyr Tyr top top G ys ys top Trp U Leu Leu Leu Leu ro ro ro ro is is Gln Gln G rg rg rg rg U Ile Ile Ile t Thr Thr Thr Thr sn sn Lys Lys G er er rg rg G U Val Val Val Val la la la la sp sp Glu Glu G Gly Gly Gly Gly D : -T-G-GTtranscription replication (error) -TG-G-GTtranscription mr : -UU-GG-U- -U-GG-U- rotein fragment : translation -Ile-Gly-Leu- translation -Thr-Gly-Leu- 6. hown below are the structures of adenine (), guanine (G), thymine (T) and cytosine (). lease show the hydrogen bonds between the appropriate base pairs (this will require accurate drawings. (10 pts) G T T G