Coupling in solids

Then N-Boc-O-benzylserine is coupled to the free amino group with DCC. This concludes one cycle (N° -deprotection, neutralization, coupling) in solid-phase synthesis. All three steps can be driven to very high total yields (< 99.5%) since excesses of Boc-amino acids and DCC (about fourfold) in CHjClj can be used and since side-reactions which lead to soluble products do not lower the yield of condensation product. One side-reaction in DCC-promoted condensations leads to N-acylated ureas. These products will remain in solution and not reaa with the polymer-bound amine. At the end of the reaction time, the polymer is filtered off and washed. The times consumed for 99% completion of condensation vary from 5 min for small amino acids to several hours for a bulky amino acid, e.g. Boc-Ile, with other bulky amino acids on a resin. A new cycle can begin without any workup problems (R.B. Merrifield, 1969 B.W. Erickson, 1976 M. Bodanszky, 1976). 

The model of the chain of hydrogen atoms with a completely delocalized (metallic) type of bonding is outlined in the preceding section. Intuitively, a chemist will find this model rather unreal, as he or she expects the atoms to combine in pairs to give H2 molecules. In other words, the chain of equidistant H atoms is expected to be unstable, so it undergoes a distortion in such a way that the atoms approach each other in pairs. This process is called Peierls distortion (or strong electron-phonon coupling) in solid-state physics ... 

The reagents and methods employed for coupling in solid-phase synthesis are the same as for synthesis in solution, but a few are excluded because they are unsuitable. The mixed-anhydride method (see Section 2.6) and l-ethoxycarbonyl-2-ethoxy-l,2-dihydroquinoline (see Section 2.15) are not used because there is no way to eliminate aminolysis at the wrong carbonyl of the anhydride. Acyl azides (see Section 2.13) are too laborious to make and too slow to react. The preparation of acyl chlorides (see Section 2.14) is too complicated for their routine use this may be rectified, however, by the availability of triphosgene (see Section 7.13). That leaves the following choices, bearing in mind that a two to three times molar excess of protected amino acid is always employed. 

E Falb, T Yechezkel, Y Salitra, C Gilon. In situ generation of Fmoc-amino acid chlorides using >/s-(trich loro methyl (carbonate and its utilization for difficult couplings in solid-phase peptide synthesis. J Pept Res 53, 507, 1998. 

A Thaler, D Seebach, FC Cardinaux. Lithium-salt effects in peptide synthesis. Part II. Improvement of degree of resin swelling and efficiency of coupling in solid-phase synthesis. Helv ChimActa 74, 628, 1991. 

Scheme 2 Tentative rationalization of the production of cross-linked yellow chromophores by near-UV irradiation of quinol A and quinone D couple in solid carbohydrate matrix.

Robinson, H., H. G. Dehmelt, and W. Gordy Nuclear Quadrupole Couplings in Solid Bromides and Iodides. J. chem. Physics 22, 511—515 (1954). 

Yamashiro, D., Blake, J., and Li, C. H. (1976) The use of trifluoroethanol for improved coupling in solid-phase peptide synthesis. Tetrahedron Lett. 17,1469-1472. Milton, S. C. and Milton, R. C. (1990) An improved solid-phase synthesis of a difficult-sequence peptide using hexafluoro-2-propanol. Int. J. Pept. Protein Res. 36, 193-196. 

Table 3 Schedule for DCC Coupling in Solid-phase Synthesis of Somatostatin-14 ...

In an abundant h spin system, H- h homonuclear dipolar coupling in solids is very large and the H signal is broadened to about 50 kHz. Since this large ll linewidth is sufficiently larger than the typical MAS rate of several kHz, we cannot observe the H high resolution NMR spectrum in solids by only using the MAS method. Under these situations, it is very useful to use multiple... 

In theoretical works [82, 83] the potential of coupling in solid Ceo doped by alkaline metals was estimated. It was concluded that the coupling dominates in the vibrational modes of Hg and Ag symmetry. Thus the coupling is distributed... 

Prior to ENDOR analyses of the soliton spin density, the 7t-electron nature of the soliton has been confirmed from the studies of the anisotropy of ESR and ENDOR spectra in stretch-oriented samples, [54,98] by noticing that 7t-elcctron shows characteristic anisotropy of g value and hyperfine coupling in solids [5]. The results have justified the use of the theory of 7i-electroii in subsequent ENDOR and other magnetic-resonance analyses. 

An improved variant of the popular double cross-polarisation (DCP) experiment for heteronuclear dipolar re-coupling in solid state NMR spectroscopy under MAS was introduced by Bjerring and Nielsen. By simple phase and amplitude modulation of the RF irradiation at the Hartman-Hahn sideband conditions, the new pulse sequence, dubbed iDCP, was shown to enable broadband excitation with the high efficiency of y-encoded coherence transfer. The efficiency and robustness of iDCP towards isotropic chemical shift variations and chemical shift anisotropies in the case of uniformly C, N-labelled proteins has been demonstrated numerically and experimentally by N to C coherence transfer for N-labelled N-Ac-L-valyl-L-leucine and C, N-labelled-L-threonine. 

S.A. oyce,. R. Yates, C.. Pickard, P. Mauri, A first principles theory of nuclear magnetic resonance -coupling in solid-state systems,. Chem. Phys. 127 (2007) 204107. 

Aromatic aldehydes and ketones undergo pinacol coupling in solid state by Zn-ZnCl reagent to give a mixture of the reduced product (0-2%) along with major amount (45-80%) of the coupled product (glycol) (Scheme 32). 

In a similar way propargyl alcohols could be coupled in solid state (Scheme 36). 

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