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Huang, K.; Wu, C. W.; Sanborn, T. J.; Patch, J. A.; Kirshenbaum, K.; Zuckermann, R. N.; Barron, A. E.; Radhakrishnan, I. J. Am. Chem. Soc. 2006, 128, 1733-1738.
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64349123769
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We also were able to synthesize s2ne (5b) from 2′-nitroacetophenone via a selective reduction of the ketone to the R-alcohol, conversion to the S-azide, and reduction to the S-amine, similar to the work of Gorske et al, see ref 16, However, the overall yield of 5b was significantly lower using this approach 12, data not shown
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We also were able to synthesize s2ne (5b) from 2′-nitroacetophenone via a selective reduction of the ketone to the R-alcohol, conversion to the S-azide, and reduction to the S-amine, similar to the work of Gorske et al. (see ref 16). However, the overall yield of 5b was significantly lower using this approach (12%, data not shown).
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20844441945
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Coe, J. W.; Brooks, P. R.; Vetelino, M. G.; Wirtz, M. C.; Arnold, E. P.; Huang, J.; Sands, S. B.; Davis, T. I.; Lebel, L. A.; Fox, C. B.; Shrikhande, A.; Heym, J. H.; Schaeffer, E.; Rollema, H.; Lu, Y.; Mansbach, R. S.; Chambers, L. K.; Rovetti, C. C.; Schulz, D. W.; Tingley, F. D., III; O'Neill, B. T. J. Med. Chem. 2005, 48, 3474-3477.
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J. Med. Chem
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Coe, J.W.1
Brooks, P.R.2
Vetelino, M.G.3
Wirtz, M.C.4
Arnold, E.P.5
Huang, J.6
Sands, S.B.7
Davis, T.I.8
Lebel, L.A.9
Fox, C.B.10
Shrikhande, A.11
Heym, J.H.12
Schaeffer, E.13
Rollema, H.14
Lu, Y.15
Mansbach, R.S.16
Chambers, L.K.17
Rovetti, C.C.18
Schulz, D.W.19
Tingley III, F.D.20
O'Neill, B.T.21
more..
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29
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84869269838
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1H NMR (>95%) and HPLC (96% purity at 220 nm).
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1H NMR (>95%) and HPLC (96% purity at 220 nm).
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84869269839
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We synthesized and characterized an o-methyl analogue of peptoid 9 as a steric control. As (S)-1-(2-methylphenyl)ethylamine was not commercially available, we utilized 2-methylbenzylamine (2mb) for this control peptoid (V2mb(Vspe)8, The removal of the α-methyl group on the N-terminal side chain in this peptoid (and in similar nonamers we have studied) appears to strengthen the threaded loop (data not shown, We believe this may be due to an electronic effect, as the lack of an α-methyl group should decrease electron density at the N-terminal ammonium. Since we were unable to make direct comparisons between the control N2mb(Nspe)8 and peptoid 9, we omit this relatively complex analysis here for brevity
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We synthesized and characterized an o-methyl analogue of peptoid 9 as a steric control. As (S)-1-(2-methylphenyl)ethylamine was not commercially available, we utilized 2-methylbenzylamine (2mb) for this control peptoid (V2mb(Vspe)8). The removal of the α-methyl group on the N-terminal side chain in this peptoid (and in similar nonamers we have studied) appears to strengthen the threaded loop (data not shown). We believe this may be due to an electronic effect, as the lack of an α-methyl group should decrease electron density at the N-terminal ammonium. Since we were unable to make direct comparisons between the control N2mb(Nspe)8 and peptoid 9, we omit this relatively complex analysis here for brevity.
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31
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64349108878
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We note that DMSO may be able to disrupt hydrogen bonding in a threaded loop-type structure based on a qualitative comparison of the NMR spectra of 2 in acetonitrile-d3 and DMSO-d6; see the Supporting Information, Therefore, the cis/trans ratio determined for 7 may be higher in DMSO relative to acetonitrile. We include the DMSO-d3 data here to provide our most comprehensive analysis of peptoid 7
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3 data here to provide our most comprehensive analysis of peptoid 7.
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32
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64349106925
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Similar blue shifts in CD spectra for peptoids containing Nsnp residues have been observed previously; see ref 7a
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Similar blue shifts in CD spectra for peptoids containing Nsnp residues have been observed previously; see ref 7a.
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33
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64349115653
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For a space-filling model of the threaded loop structure adopted by nonamer 2, see Figure 4 in ref 10.
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For a space-filling model of the threaded loop structure adopted by nonamer 2, see Figure 4 in ref 10.
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34
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Assignments in the 1D 1H NMR spectrum for 9 were corroborated by 2D NOESYdata. See theSupporting Informationforthe 1D1HNMRspectrum of peptoid 9.
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Assignments in the 1D 1H NMR spectrum for 9 were corroborated by 2D NOESYdata. See theSupporting Informationforthe 1D1HNMRspectrum of peptoid 9.
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Boyer, R. D.; Johnson, R.; Krishnamurthy, K. J. Maen. Reson. 2003, 165, 253-259.
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(2003)
J. Maen. Reson
, vol.165
, pp. 253-259
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Boyer, R.D.1
Johnson, R.2
Krishnamurthy, K.3
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