Manual Solid-Phase Synthesis

The original Merrifield reaction vessel was made from a glass tube and equipped with a side opening and a porous glass frit to facilitate the separation of solid and liquid phases 

PRACTICAL ASPECTS OF COMBINATORIAL SOLID-PHASE SYNTHESIS 

---

Manual Solid-Phase Synthesis of Glutathione Analogs... 

Manual solid-phase synthesis requires intervention by a chemist during the assembly of a biopolymer. A manual synthesis can vary from manual addition of all reagents and solvents to manual intervention at a single step (such as addition of the monomer). 

Figure 3.17. Traditional reaction vessels for manual solid-phase synthesis. (From http //www. pepnet.com/).

A wide choice of peptide synthesizers is currently available, ranging from manual to fully automated. They are all based on solid-phase peptide synthesis methodologies in which either f-butoxy carbonyl (t-boc) (11), or 9-fluor-enylmethoxycarbonyl (Fmoc) (12) is the major protecting group during synthesis. A detailed description of peptide synthesis is clearly beyond the scope of this chapter, and further information on practical and theoretical approaches to this chemistry may be found elsewhere (13-15). However, a brief outline of solid-phase synthesis may prove useful. 

Solid-phase synthesis of the peptide was carried out manually on a Rink amide resin (435 mg, substitution level 0.46 mmol -g 1) applying the Fmoc strategy. After removal of the Fmoc group attached to the resin with 20% piperidine in DMF (20 min), Fmoc-Tyr(tBu)-OH (230 mg, 0.5 mmol) was introduced with DIC (78 pL, 0.5 mmol) in the presence of HOBt (68 mg, 0.5 mmol) (reaction time 2h). After... 

Peptides were prepared manually by stepwise solid-phase synthesis methodology using conventional N"-Boc chemistry. Briefly, copoly(styrene/l% DVB)-pMeBHA-HCl resin, [100-200 mesh (substitution... 

Solid Phase Synthesis of a Chimeric Peptide With Boc Strategy The peptide was manually synthesized on MBHA resin (1.1 mmol/g capacity). 

Key Words Automation parallel synthesis solid phase synthesis manual synthesizer centrifugation review. 

Instrumentation for Manual Solid-Phase Peptide Synthesis... 

Montanari, V. and Kumar, K. (2006) A fluorous capping strategy for Fmoc-based automated and manual solid-phase peptide synthesis. European Journal of Organic Chemistry, (4), 874-877. 

The differentiation between a combination of one of these reaction blocks and a magnetic stirplate and a manual synthesizer is largely arbitrary. Versatile manual synthesizers (Table 3) that can be used for both solution- and solid-phase synthesis range from the aapptec Labmate to the Biichi Syncore, Chemspeed MSW 500, and Heidolph Synthesis 1 (Fig. 5). The Biichi Syncore can be equipped with a concentrator cover, which converts it into a parallel evaporator, or -with a filtration unit that permits top filtration from the reaction mixture and collection of the filtrate (Fig. 5). 

Synthesis on solid supports was first developed by Merrifield [1] for the assembly of peptides. It has expanded to include many different applications including oligonucleotide, carbohydrate, and small-molecule assembly (see Chapters 11 and 14). The repetitive cycle of steps involved in the solid-phase synthesis of biopolymers can be performed manually using simple laboratory equipment or fully automated with sophisticated instrumentation. This chapter examines typical solid-phase reaction kinetics to identify factors that can improve the efficiency of both manual and automated synthesis. The hardware and software features of automated solid-phase instruments are also discussed. The focus of this discussion is not on particular commercial model synthesizers but on the basic principles of instrument operation. These considerations can assist in the design, purchase, or use of automated equipment for solid-phase synthesis. Most contrasting features have advantages and disadvantages and the proper choice of instrumentation depends on the synthetic needs of the user. 

---