500
Helvetica Chimica Acta Vol. 85 (2002)
Table 2. MS Fragments of Peptides from Single-Bead Analysis
Sequence
Molecular peak b-Fragments
y-Fragments
1
2
3
4
1
2
3
4
5
Gln-Arg-Pro-Tyr-Gly
Phe-Pro-Met-Lys-Thr
Trp-Tyr-Ser-His-Glu
Met-Phe-Gln-Gly-Ile
Phe-Leu-Ser-Val-Arg
Ile-Gly-Glu-Pro-His
620
639(ox)
720
595
621
285
239336 24/4975
120 248 379 476
285 372 535
245 376 504
132 279
464/480 143 189 317 464
175 274 361 474
261
552
114 186 299 397
186 299
156 253 380 439 535
439 552 721
Ala-Asn-Ile-Gly-Glu- 737
Pro-His
sequencing by tandem MS. Accordingly, this method is suitable for fast analysis of, e.g.,
−split & mix libraries× of short peptides.
Experimental Part
General. For all syntheses, PEGA-resin (PL-PEGA, 0.2 mol-equiv./g, Polymer Labs.) modified with N-
methylglycine (sarcosine) was used. All solvents and reagents were commercially available and used without
further purifications. UV/VIS Spectra: Kontron Instruments UVIKON 860. HPLC Analyses: Hewlett-Packard
HPLC1050 with YMC-Pack ProC18, AS-300 column. IR Spectra (cmÀ1): Nicolet 20 SXB FTIR and Nicolet 550
for analyses of single beads. NMR Spectra: Bruker 400 (if not stated otherwise) with SiMe4 as internal standard
at 300 K. MS Spectra: Perkin-Elmer Sciex API III.
2-({2-[1,1-Bis(4-methoxyphenyl)-1-phenylmethoxy]ethyl}disulfanyl)ethanol (1). To a soln. of 2-[(2-hydrox-
yethyl)disulfanyl]ethanol (9.5 ml, 78 mmol) in anh. pyridine (5 ml), a soln. of 4.4'-Dimethoxytriphenylmethyl
chloride (20.5 g, 60 mmol) in anh. pyridine (100 ml) was added within 2 h under stirring at r.t. The mixture was
stirred for 16 h under N2, quenched within 30 min with MeOH (20 ml), poured on H2O (50 ml), and extracted
with CH2Cl2. The combined org. layers were washed with sat. aq. NaCl soln., dried (MgSO4), and co-evaporated
azeotropically with toluene to yield a dark yellow oil. The residue was purified by CC (SiO2; hexane/t-BuOMe
1:1 containing 2% of Et3N) to furnish 1 as a highly viscous yellow oil (15 g, 55%). IR (KBr): 3432, 1736, 1608,
1
1445, 1251, 1070. H-NMR (250 MHz, (CD3)2SO): 2.68 (t, 2 H, J 6.48); 3.53 3.58 (m, 2 H, J 6.2, 5.8); 2.91
(t, 3 H, J 6.01); 3.21 (t, 2 H, J 6.09); 3.73 (s, 6 H); 4.84 (t, 1 H, J 5.4); 6.8 7.4 (m, 13 H). 13C-NMR
(100 MHz, CDCl3): 41.4, 46.12, 55.4, 59.84, 62.07, 86.04, 113.56, 127.0 128.2, 130.03, 136.04, 145.25, 158.49. ESI-
MS: 456 (M) , 379([ M À C6H5 ] ), 303 (DMT )4). ISP-MS: 303 (DMT ). ISN-MS: 515 ([M Ni] ). Anal.
calc. for C25H28O4S2: C 65.76, H 6.18, S 14.04; found: C 65.93, H 6.49, S 13.17.
13-Bis(4-methoxyphenyl)-13-phenyl-4-oxo-8,9-dithia-5,12-dioxatridecanoic Acid (2). Alcohol 1 (15 g,
33 mmol), succinic anhydride (10.1 g, 90 mmol), and DMAP5) (12 g, 99 mmol) were dissolved in anh. pyridine
(120 ml) and CH2Cl2 (120 ml) at r.t. The mixture was stirred for 24 h under N2, poured on 1% aq. acetic acid
soln. (500 ml), and extracted with CH2Cl2. The combined org. layers were washed with sat. aq. NaCl soln., dried
over MgSO4, and evaporated. The remaining pyridine was co-evaporated with toluene, leaving a brown oily
residue, which was purified by CC (SiO2; MeOH/AcOEt 1:9containing 2% of Et 3N) to yield 2 (12.1 g, 66%) as
a highly viscous yellowish oil. IR (KBr): 2496, 1737, 1608, 1445, 1251, 1157, 1170, 1034, 832. 1H-NMR
((CD3)2SO): 2.6 (m, 4 H); 2.79( t, J 6.4, 2 H); 2.86 (t, J 6.4, 2 H); 3.36 (t, J 6.4, 2 H); 3.79( s, 6 H); 4.28
(t, J 6.6, 2 H); 6.9, 7.2 7.4 (m, 13 H). 13C-NMR (100 MHz, CDCl3): 41.4, 55.4, 59.84, 86.04, 113.52, 127.0
128.2, 130.45, 136.04, 145.25, 158.49. ISN-MS: 555 ([M À H] ). Anal. calc. for C29H32O7S2: C 62.57, H 5.79,
S 11.52; found: C 61.45, H 6.14, S 9.29.
Coupling of 2 to the PEGA resin. To 700 mg of PEGA resin (ca. 0.14 mmol, 4.8 g in MeOH), rinsed with
NMP6), a preactivated linker-soln. in NMP was added, consisting of 950 ml of a 0.5m (0.42 mmol) soln. of
4
)
)
)
DMT represents the [1,1-Bis(4-methoxyphenyl)-1-phenyl]methyl group.
DMAP represents 4-(dimethylamino)pyridine.
NMP stands for N-methyl-2-pyrrolidon.
5
6