Solids molecular synthesis

Rapid purification Stir over CaH2 (5% w/v) overnight, filter, then distil at 20mmHg. Store the distd DMF over 3A or 4A molecular sieves. For solid phase synthesis, the DMF used must be of high quality and free from amines. 

Keywords Co-assembly Functionalization Molecular dynamics Self-assembly Solid phase synthesis... 

Certain types of molecules, especially polypeptides and polynucleotides, lend themselves to synthesis on solid supports. In such syntheses, the starting material is attached to a small particle (bead) or a surface and the molecule remains attached during the course of the synthetic sequence. Solid phase synthesis also plays a key role in creation of combinatorial libraries, that is, collections of many molecules synthesized by a sequence of reactions in which the subunits are systematically varied to create a range of structures (molecular diversity). 

To illustrate the diversity of strategies available for solid-phase synthesis, several fairly recent protein syntheses can be cited. SRY, an 80-residue DNA binding protein, was syn-thesized[62] on a Pepsyn support (polyacrylamide gel beads) in a continuous flow machine using Fmoc/tBu protection and TBTU/HOBt activation. HPLC gave a homogeneous product with molecular weight 10051 Da (calculated 10033 Da). It bound to DNA, as expected. 

Peptides These are made up of approximately 20 to 40 amino acids, with molecular weights typically below 5000 Da, and are produced by chemical synthesis, primarily via solid-phase synthesis. The manufacture of pephdes is thus closer to that of small molecules than to biological processes such as fermentahon. 

Jones, L. Schumm, J. S. Tour, J. M. Rapid Solution and Solid Phase Synthesis of OHgo(l,4-phenyleneethynylene)s with Thioester Termini Molecular Scale Wires with Alligator Clips. Derivation of Iterative Reaction Efficiencies on a Polymer Support, J. Org. Chem. 1997, 62, 1388-1410. 

Such products may be screened directly without any further purification. Because no purification on the final products is required in such instances, parallel solid-phase synthesis can be used to prepare arrays of compounds with a broad range of lipophilicity, charge, and molecular weight.9 Such arrays would be difficult to prepare by parallel solution-phase chemistry not only because each compound would require a different work-up strategy, but also because the purification of small, hydrophilic molecules is often a difficult task. 

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