Photoelastic Abc Amino Acids
NMR (200 MHz, CDCl3) δ 1.25 (s, 9H), 7.30-8.30 (m, 8H); 13C
NMR (50 MHz, CDCl3) δ 27.6, 81.6, 120.3, 120.4, 128.0, 128.9,
130.3, 130.5, 131.2, 132.6, 135.5, 140.2, 143.4, 165.5, 167.2;
HRMS-FAB (M + Na+) calcd for C17H17NNaO3 306.1106, found
306.11167.
EtOAc, 4:1); IR (CCl4) 3454, 3067, 2979, 2930, 2359, 1729, 1549,
1
1509, 1247, 776 cm-1; H NMR (300 MHz, CDCl3) δ 1.25 (s,
9H), 4.17 (t, 1H, J ) 6.9 Hz), 4.38 (d, 2H, J ) 7.2 Hz), 4.41 (d,
2H, J ) 7.2 Hz), 5.00 (t, 1H, J ) 5.9 Hz), 7.10-7.60 (m, 17H),
7.74 (d, 2H, J ) 7.2 Hz), 7.85 (dd, 1H, J ) 7.7, 1.4 Hz), 7.87-
7.97 (m, 4H); 13C NMR (50 MHz, CDCl3) δ 27.6, 42.9, 47.3, 66.7,
81.4, 119.9, 122.2, 122.4, 122.5, 123.1, 125.0, 127.1, 127.5, 127.6,
127.7, 128.2, 128.5, 128.7, 129.2, 130.0, 130.6, 130.9, 131.4, 131.6,
132.8, 135.7, 140.7, 141.3, 141.7, 143.0, 143.9, 152.2, 152.6, 156.4,
167.8; HRMS-FAB (M + Na+) calcd for C45H39N3NaO4 708.28383,
found 708.28360.
4-(4-Nitrosophenyl)-benzoic Acid tert-Butyl Ester (12d). The
procedure was the same as for 12a; from 300 mg (1.0 mmol) of
nitro compound 11d in 10 mL of 2-methoxyethanol was obtained
230 mg (81%) of 12d as a green solid: TLC Rf ) 0.36 (hexanes/
CH2Cl2, 1:1); IR (CHCl3) 3055, 2984, 2312, 2260, 1709, 1297 cm-1
;
1H NMR (200 MHz, CDCl3) δ 1.61 (s, 9H), 7.68 (d, 2H, J ) 8.2
Hz), 7.82 (d, 2H, J ) 8.3 Hz), 7.97 (d, 2H, J ) 8.3 Hz), 8.09 (d,
2H, J ) 8.2 Hz); 13C NMR (50 MHz, CDCl3) δ 28.2, 81.4, 121.5,
127.3, 128.1, 130.1, 131.3, 142.9, 146.9, 164.7, 165.2; HRMS-
FAB (M + Na+) calcd for C17H17NNaO3 306.1106, found
306.11129.
[1,1′-Biphenyl]-4-carboxylic Acid, 4′-[[4′-[[[(9H-Fluoren-9-
ylmethoxy)carbonyl] amino]methyl][1,1′-biphenyl]-4-yl]azo], 1,1-
Dimethylethyl Ester (Fmoc-ppAbc-Ot-Bu, 13d). From 140 mg
(0.33 mmol) of amine 9d and 95 mg (0.33 mmol) of nitroso
compound 12d in 5 mL of AcOH was obtained 194 mg (85%) of
13d as a pale orange solid (mp 202-204 °C, dec after 210 °C):
TLC Rf ) 0.21 (trans), 0.10 (cis) (CHCl3/hexanes, 50:1); IR (KBr)
General Procedure for Preparation of Fmoc-Abc-Ot-Bu
Isomers (13a-d). The indicated amounts of amine and nitroso
compound were combined in glacial acetic acid and stirred at room
temperature for 24 h. The solvent was removed in vacuo, and the
residue was purified by flash chromatography with 4:1 hexanes/
EtOAc for mxAbc derivatives 13a-c or with 50:1 CHCl3/hexanes
for the ppAbc derivative 13d. In all cases, the fractions containing
the well-separated cis and trans isomers were combined. NMR data
are reported for the trans isomer of each compound.
1
3388, 2361, 2345, 1724, 1689, 1521, 1301, 1224 cm-1; H NMR
(300 MHz, CDCl3) δ 1.64 (s, 9H), 4.24 (t, 1H, J ) 6.6 Hz), 4.44
(d, 2H, J ) 5.8 Hz), 4.48 (d, 2H, J ) 6.7 Hz), 5.15 (br t, 1H, J )
5.8 Hz), 7.31 (t, 2H, J ) 7.2 Hz), 7.35-7.44 (m, 4H), 7.61 (d, 2H,
J ) 8.7 Hz), 7.64 (d, 2H, J ) 8.1 Hz), 7.68-7.82 (m, 8H), 8.026
(d, 2H, J ) 8.4 Hz), 8.034 (d, 2H, J ) 8.7 Hz), 8.08 (d, 2H, J )
8.7 Hz); 13C NMR (50 MHz, CDCl3) δ 28.2, 44.5, 47.3, 66.7, 81.2,
120.0, 123.5, 125.0, 126.9, 127.1, 127.5, 127.6, 127.7, 127.9, 128.1,
130.0, 131.3, 138.2, 139.4, 141.3, 142.6, 143.3, 143.9, 144.0, 151.9,
152.3, 165.5; HRMS-FAB (M + Na+) calcd for C45H39N3NaO4
708.28383, found 708.28403.
[1,1′-Biphenyl]-4-carboxylic Acid, 3′-[[4′-[[[(9H-Fluoren-9-
ylmethoxy)carbonyl] amino]methyl][1,1′-biphenyl]-3-yl]azo]
(Fmoc-mpAbc-OH). Fmoc-mpAbc-Ot-Bu 13a (200 mg, 29.2
mmol) was dissolved in 10 mL of TFA/H2O (95:5) and stirred at
room temperature for 2 h. The product was evaporated to dryness
in vacuo, suspended in ether, and collected by filtration to afford
156 mg (85%) of the desired product as a yellow solid: 1H NMR
(200 MHz, DMSO-d6) δ 4.16-4.25 (m, 1H), 4.24 (d, 2H, J ) 6.1
Hz), 4.36 (d, J ) 6.7 Hz), 7.26-7.46 (m, 6H), 7.64-7.78 (m, 6H),
7.83-8.00 (m, 9H), 8.06 (d, 2H, J ) 8.1 Hz), 8.19 (br s, 1H), 8.26
(br s, 1H); 13C NMR (50 MHz, DMSO-d6) δ 43.4, 46.7, 65.3, 120.0,
120.9, 121.1, 121.3, 122.0, 125.1, 126.7, 127.0, 127.5, 127.7, 129.7,
129.8, 130.0, 130.1, 130.2, 137.6, 139.6, 140.3, 140.7, 141.2, 143.2,
143.8, 152.4, 156.3, 167.0; LRMS-FAB (M + H+) calcd for
C41H32N3O4 630, found 630 (FAB). Efforts to obtain a high-
resolution mass spectrum were unsuccessful.
Synthesis of Model Peptide STPPK(mpAbc)KKRKV. All
amino acids had NR-Fmoc protection and side chain protecting
groups as follows: t-Bu for Ser and Thr, Boc for Lys, and 2,2,5,7,8-
pentamethyl-chroman-6-sulfonyl (Pmc) for Arg. Synthesis was
performed manually using a Burrell wrist-action shaker and a glass
reaction vessel derived from a fritted glass Bu¨chner funnel by the
addition of a threaded top and a Teflon stopcock in the stem. Fmoc-
valyl Wang resin (125 mg, 0.80 mmol/g) was swelled by shaking
in 5 mL of NMP for 30 min and drained by suction. Cycles of
deprotection and synthesis were performed as follows. Deprotection
was effected by shaking the resin for 15-20 min in 5 mL of 20%
(v/v) piperidine in NMP; the deprotection cocktail was removed
by suction, and the resin was rinsed by shaking for 5 min each
with 5-10 mL portions of NMP (3×) and 2-propanol (3×).
Coupling: to 0.2 mmol of protected amino acid in 0.8 mL of NMP
in the reaction vessel was added PyBOP (0.2 mmol in 0.4 mL of
NMP), 1-hydroxybenzotriazole (HOBt, 0.2 mmol in 0.4 mL of
NMP), and DIPEA (0.4 mmol, 66 µL); the mixture was shaken for
2 h, drained, and washed with 5-10 mL portions of NMP (6×).
For mpAbc, 0.15 mmol of protected amino acid with proportionate
amounts of other reaction components and a coupling time of 3 h
were employed.
[1,1′-Biphenyl]-4-carboxylic Acid, 3′-[[4′-[[[(9H-Fluoren-9-
ylmethoxy)carbonyl] amino]methyl][1,1′-biphenyl]-3-yl]azo], 1,1-
Dimethylethyl Ester (Fmoc-mpAbc-Ot-Bu, 13a). From 1.20 g
(2.9 mmol) of amine 9a and 810 mg (2.9 mmol) of nitroso
compound 12a in 50 mL of AcOH was obtained 1.69 g (86%) of
13a as a yellow oil: TLC Rf ) 0.24 (trans), 0.15 (cis) (hexanes/
EtOAc, 4:1); IR (CCl4) 3461, 3023, 2984, 2940, 2906, 1745, 1373,
1240, 776 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.64 (s, 9H), 4.24
(t, 1H, J ) 6.7 Hz), 4.44 (d, 2H, J ) 6.0 Hz), 4.49 (d, 2H, J ) 6.9
Hz), 5.26 (br s, 1H), 7.27-7.44 (m, 6H), 7.56-7.80 (m, 12H) 7.94
(br d, 1H, J ) 8.1 Hz), 7.97 (dt, 1H, J ) 8.4, 1.8 Hz) d, 8.11 (d,
2H, J ) 8.4, 1.2 Hz), 8.18 (br s, 1H), 8.22 (t, 2H, J ) 1.8 Hz); 13
C
NMR (50 MHz, CDCl3) δ 28.3, 44.8, 47.3, 66.7, 81.2, 120.0, 121.7,
121.8, 122.4, 125.0, 127.0, 127.1, 127.5, 127.7, 128.1, 129.6, 129.7,
130.1, 131.2, 138.1, 139.5, 141.2, 141.4, 141.8, 143.9, 144.2, 153.0,
153.1, 156.5, 165.6; HRMS-FAB (M + Na+) calcd for C45H39N3-
NaO4 708.28383, found 708.28437.
[1,1′-Biphenyl]-3-carboxylic Acid, 3′-[[3′-[[[(9H-Fluoren-9-
ylmethoxy)carbonyl] amino]methyl][1,1′-biphenyl]-3-yl]azo], 1,1-
Dimethylethyl Ester (Fmoc-mmAbc-Ot-Bu, 13b). From 128 mg
(0.28 mmol) of amine 9b and 80 mg (0.28 mmol) of nitroso
compound 12b in 5 mL of AcOH was obtained 150 mg (78%) of
13b as a yellow oil: TLC Rf ) 0.25 (trans), 0.15 (cis) (hexanes/
EtOAc, 4:1); IR (CCl4) 3452, 2981, 2929, 2856, 2322, 1717, 1549,
1512, 1264, 1218, 776 cm-1; 1H NMR (300 MHz, CDCl3) δ 1.63
(s, 9H), 4.23 (t, 1H, J ) 6.8 Hz), 4.36-4.49 (m, 4H), 5.20 (br s,
1H), 7.26-7.33 (m, 3H), 7.37 (t, 2H, J ) 7.2 Hz), 7.45 (t, 1H, J
) 7.8 Hz), 7.52 (t, 1H, J ) 7.8 Hz), 7.56-7.65 (m, 5H), 7.73 (t,
2H, J ) 7.8 Hz), 7.69-7.78 (m, 2H), (7.84 (ddd, 1H, J ) 7.8, 1.8,
1.2 Hz), 7.946 (dt, 1H, J ) 7.8, 1.2 Hz), 7.950 (dt, 1H, J ) 7.8,
1.5 Hz), 8.01 (dt, 1H, J ) 7.8, 1.4 Hz), 8.19 (t, 1H, J ) 1.7 Hz),
8.22 (t, 1H, J ) 1.8 Hz), 8.33 (t, 1H, J ) 1.5 Hz); 13C NMR (50
MHz, CDCl3) δ 28.2, 45.1, 47.3, 66.8, 81.3, 120.0, 121.7, 121.8,
121.9, 122.1, 125.0, 126.5, 126.9, 127.1, 127.7, 128.2, 128.7, 128.8,
129.3, 129.6, 129.66, 129.72, 129.8, 130.0, 131.2, 132.7, 139.1,
140.5, 140.8, 141.3, 141.4, 141.9, 143.9, 153.05, 153.09, 156.5,
165.7; HRMS-FAB (M + Na+) calcd for C45H39N3NaO4 708.28383,
found 708.28442.
[1,1′-Biphenyl]-2-carboxylic Acid, 3′-[[2′-[[[(9H-Fluoren-9-
ylmethoxy)carbonyl] amino]methyl][1,1′-biphenyl]-3-yl]azo], 1,1-
Dimethylethyl Ester (Fmoc-moAbc-Ot-Bu, 13c). From 150 mg
(0.36 mmol) of amine 9c and 105 mg (0.36 mmol) of nitroso
compound 12c in 7 mL of AcOH was obtained 200 mg (80%) of
13c as a yellow oil: TLC Rf ) 0.26 (trans), 0.16 (cis) (hexanes/
Deprotection and cleavage were performed on 30% of the resin
with 1 mL of 95:5 (v/v) TFA/water for 2 h at room temperature
J. Org. Chem, Vol. 71, No. 21, 2006 7965