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, is, and Lys d) Met and Cys e) Asp and Glu f) Pro, Trp, Asn, Gln, Ser, Thr, Tyr, Cys, Asp, Glu, Arg, is, and Lys 25.4. 3 C d) 2 e) f) 25.5. Arginine has a basic side chain, while asparagine does not. At a p of 11, arginine exists predominantly in a form in which the side chain is protonated. Therefore, it can serve as a proton donor. 25.6. Tyrosine possesses a phenolic proton which is more readily deprotonated because deprotonation forms a resonance-stabilized phenolate ion. In contrast, deprotonation of the group of serine gives an alkoxide ion that is not resonance-stabilized. As a result, the group of tyrosine is more acidic than the group of serine.
670 CAPTER 25 25.7. 2.77 5.98 9.74 d) 6.30 25.8. aspartic acid glutamic acid 25.9. Leucine and isoleucine 25.10. The pi of = 5.48, the pi of Trp = 6.11, and the pi of Leu = 6.00. At p = 6.0, will travel the farthest distance. At p = 5.0, Trp will travel the farthest distance. 25.11. 25.12. 1) Br 2, PBr 3 2) 2 3) excess 3 2 (racemi 1) Br 2, PBr 3 2) 2 3) excess 3 2 (racemi 1) Br 2, PBr 3 2) 2 3) excess 3 2 (racemi
CAPTER 25 671 25.13. C C C 2 2 2 2 C Leucine Valine nylalanine d) Glycine 25.14. 1) aet Et Et 2) Br 2 3) 3 +, heat 1) aet Et Et 2) C 3 Br 3) 3 +, heat 2 1) aet Et Et 2) Br 2 3) 3 +, heat 25.15. 2 2 2 alanine valine leucine 25.16. Leucine can be prepared via the amidomalonate synthesis with higher yields than isoleucine, because the former requires an S 2 reaction with a primary alkyl halide, while the latter requires an S 2 reaction with a secondary (more hindered) alkyl halide.
672 CAPTER 25 25.17. S 1) 4 Cl, ac 2) 3 + S 2 1) 4 Cl, ac 2) 3 + 2 1) 4 Cl, ac 2) 3 + 2 1) 4 Cl, ac d) 2) 3 + 2 25.18. 3 C 1) 4 Cl, ac 2) 3 + 3 C 2 alanine 1) 4 Cl, ac 2) 3 + 2 leucine 1) 4 Cl, ac 2) 3 + 2 valine 25.19. 2 C Ac Ac Ac d) Ac
CAPTER 25 673 25.20. Glycine does not possess a chirality center, so the use of a chiral catalyst is unnecessary. Also, there is no alkene that would lead to glycine upon hydrogenation. 25.21. 2 S 2 C S 2 2 25.22. Leu-Ala--Cys-Asp or L-A-F-C-D. 25.23. Cys-Tyr-Leu 25.24. Constitutional isomers 25.25. 2 C terminus terminus 25.26. Steric hindrance results from the phenyl groups: 2
674 CAPTER 25 25.27. 2 S S 2 25.28. C 2 C 2 C 2 C 2 25.29. D-Glutamic acid ot naturally occurring L-Leucine L-Isoleucine L-Lysine S 2 ot naturally occurring 2 L-Isoleucine Bacitracin A L-asparagine 2 D-nylalanine D-Aspartic acid L-istidine
CAPTER 25 675 25.30. An Edman degradation will remove the amino acid residue at the terminus, and Ala is the terminus in Ala--Val. Therefore, alanine is removed, giving the following PT derivative: Ph C 3 S 25.31. Met--Val-Ala-Tyr-Lys-Pro-Val-Ile-Leu-Arg-Trp-is--Met-Cys-Arg-Gly-Pro- -Ala-Val 25.32. Ala--Val-Lys 25.33. Cleavage with trypsin will produce -Arg, while cleavage with chymotrypsin will produce Arg-. These dipeptides are not the same. They are constitutional isomers. 25.34. Trp () 2 Trp DCC 1) CF 3 C Trp Met C 3 2) a, 2 Trp Met [ + ] Met Met C 3 C 3 Ala () 2 Ala DCC 1) CF 3 C Ala Ile C 3 2) a, 2 Ala Ile [ + ] Ile Ile C 3 C 3
676 CAPTER 25 Leu () 2 Leu DCC 1) CF 3 C Leu Val C 3 2) a, 2 Leu Val [ + ] Val Val C 3 C 3 25.35. Ile () 2 Ile DCC Ile C 3 [ + ] C 3 C 3 a, 2 Ile DCC Gly C 3 Ile Gly 1) CF 3 C 2) a, 2 Ile Gly C 3
25.36. CAPTER 25 677
678 CAPTER 25 25.37. 1) Cl PLYMER 2) CF 3 C Ph -Leu-Val- 3), DCC 4) CF 3 C 5), DCC 6) CF 3 C 7), DCC 8) CF 3 C Ph 9) F 1) Cl PLYMER Ala-Val-Leu-Ile 2) CF 3 C 3), DCC 4) CF 3 C 5), DCC 6) CF 3 C 7), DCC 8) CF 3 C 9) F
CAPTER 25 679 25.38. ( terminus) Val-Ala- (C terminus) 25.39. The regions that contain repeating glycine and/or alanine units are the most likely regions to form β sheets: 25.40. Trp-is-Pro-Ala-Gly-Gly-Ala-Val-is-Cyst-Asp-Ser-Arg-Arg-Ala-Gly-Ala- 2 d) 25.41. When applying the Cahn-Ingold-Prelog convention for assigning the configuration of a chirality center, the amino group generally receives the highest priority (1), followed by the carboxylic acid moiety (2), followed the side chain (3), and finally the (4). Accordingly, the S configuration is assigned to L amino acids. Cysteine is the one exception because the side chain has a higher priority than the carboxylic acid moiety. As a result, the R configuration is assigned. 25.42. 2 C C C C C 3 2 C 2 2 C 2 Ph d) 2 C 2 C 2 25.43. Isoleucine and threonine Isoleucine = 2S,3S. Threonine = 2S,3R 25.44. S S R S S R R R 2 2 2 2 25.45. The protonated form below is highly stabilized by resonance, which spreads the positive charge over all three nitrogen atoms. 2 2 Acid 2 2
680 CAPTER 25 25.46. The protonated form below is aromatic. In contrast, protonation of the other nitrogen atom in the ring would result in loss of aromatic stabilization. 2 Acid 2 25.47. d) 25.48. 2 d) 25.49. 6.02 5.41 7.58 d) 3.22 25.50. Lysozyme is likely to be comprised primarily of amino acid residues that contain basic side chains (arginine, histindine, and lysine), while pepsin is comprised primarily of amino acid residues that contain acidic side chains (aspartic acid and glutamic acid). 25.51. 2 d)
CAPTER 25 681 25.52. 2 C R C 2 R (planar) 2 C R + C R 2 Racemic mixture 25.53. The pi of Gly = 5.97, the pi of Gln = 5.65, and the pi of Asn = 5.41. At p = 6.0, Asn will travel the farthest distance. At p = 5.0, Gly will travel the farthest distance. 25.54. d) no reaction 25.55. Methionine, valine, and glycine. The compound is highly conjugated and has a λ max that is greater than 400 nm (see Section 17.12) 25.56. 1) 4 Cl, ac 2) 3 + 2 25.57. Alanine can be prepared via the amidomalonate synthesis with higher yields than valine, because the former requires an S 2 reaction with a primary alkyl halide, while the latter requires an S 2 reaction with a secondary (more hindered) alkyl halide. 25.58. The side chain (R) of glycine is a hydrogen atom (). Therefore, no alkyl group needs to be installed at the α position. Et Et 3 +, heat 2
682 CAPTER 25 25.59. 1) Br 2, PBr 3 2) 2 2 3) excess 3 1) 4 Cl, ac 2) 3 + 2 Et Et 1) aet 2) C 3 I 3) 3 +, heat 2 25.60. 1) Br 2,PBr 3 2) 2 3) excess 3 2 (racemi 1) aet Et Et 2) Br 3) 3 +, heat 2 1) 4 Cl, ac 2) 3 + 2 25.61. 20 5 = 3,200,000 25.62. Ac
CAPTER 25 683 25.63. 1) Leu-Met-Val, 2) Leu-Val-Met, 3) Met-Val-Leu, 4) Met-Leu-Val, 5) Val-Met-Leu, 6) Val-Leu-Met 25.64. 3 3 25.65. 2 Terminus CTerminus 25.66. S S C 2 25.67. 3 25.68. 2 S 2 cysteine valine
684 CAPTER 25 25.69. tyrosine 2 2 2 serine glycine 25.70. It does not react with phenyl isothiocyanate so it must not have a free terminus. It must be a cyclic tripeptide: Gly Gly Ala Ala 25.71. Arg + Pro-Pro-Gly--Ser-Pro--Arg Arg-Pro-Pro-Gly- + Ser-Pro- + Arg 25.72. nylalanine R = S 25.73. Val-Ala-Gly: 2
CAPTER 25 685 25.74. There cannot be any disulfide bridges in this peptide, because it has no cysteine residues, and only cysteine residues form disulfide bridges. is-ser-gln-gly-thr--thr-ser-asp-tyr-ser-lys-tyr-leu-asp-ser-arg-arg-ala-gln-asp--val- Gln-Trp-Leu-Met-Asn-Thr 25.75. Prior to acylation, the nitrogen atom of the amino group is sufficiently nucleophilic to attack phenyl isothiocyanate. Acylation converts the amino group into an amide moiety, and the lone pair of the nitrogen atom is delocalized via resonance, rendering it much less nucleophilic. 25.76. 3 2 d) 3 25.77. () 2 DCC 1) CF 3 C Ala C 3 2) a, 2 Ala [ + ] Ala Ala C 3 C 3 25.78. 2 2 C 3 C 3 2 2 C 3 C 3
686 CAPTER 25 25.79. Ile () 2 Ile DCC Ile Val Leu C 3 [ + ] Val Leu C 3 Val Leu C 3 1) CF3 C 2) a, 2 Ile Val Leu 25.80. 1) Cl PLYMER Leu-Val-Ala 2) CF 3 C 3), DCC 4) CF 3 C 5), DCC 6) CF 3 C 7) F 25.81. 25.82. A proline residue cannot be part of an α helix, because it lacks an - proton and does not participate in hydrogen bonding. (The amino acid proline does indeed have an - group, but when incorporated into a peptide, the proline residue does not have an - group)
CAPTER 25 687 25.83. 2 + 25.84. Br 25.85. The stabilized enolate ion (formed in the first step) can function as a base, rather than a nucleophile, giving an E2 reaction: Et Br Et Et Et Et 25.86. The lone pair on that nitrogen atom is highly delocalized via resonance and is participating in aromaticity. Accordingly, the lone pair is not free to function as a base.
688 CAPTER 25 25.87. Br 2 Br Br 25.88. At low temperature, the barrier to rotation keeps the two methyl groups in different electronic environments (one is cis to the C= bond and the other is trans to the C= bond), and they therefore give rise to separate signals. At high temperature, there is sufficient energy to overcome the energy barrier, and the protons change electronic environments on a timescale that is faster than the timescale of the MR spectrometer. The result is an averaging effect which gives rise to only one signal. 25.89. The C group does not readily undergo nucleophilic acyl substitution because the group is not a good leaving group. By converting the C group into an activated ester, the compound can now undergo nucleophilic acyl substitution because it has a good leaving group. The nitro group stabilizes the leaving group via resonance. As described in Chapter 19, the nitro group serves as a reservoir for electron density. The nitro group must be in the ortho or para position in order to stabilize the negative charge via resonance. If the nitro group is in the meta position, the negative charge cannot be pushed onto the nitro group. 25.90. 2 Cl, 2 2 heat 2 threonine