Solid-phase organic synthesis cleavage protocols

In 1992, ACT replaced the Model 350 with the Model 396 Multiple Biomolecular Synthesizer. This instrument possesses two robotic arms, a variable speed orbital mixer, nitrogen assisted bottom filtration, a built-in ventilation system, protocols for both Fmoc and Boc synthesis and fully automated on-board cleavage for the Fmoc syntheses. It has reactor blocks of 8, 16, 40, and 96 wells for the synthesis of peptides from 5 pmol to 1 mmol. The Model 396 MBS also has a heater/cooler option for applications in solid-phase organic synthesis. 

Additionally, for comparison purposes, all steps in the solid-phase protocol (linking, cycloaddition, cleavage) were carried out both under thermal and controlled microwave heating conditions. In general, significant rate enhancements were found for each step and it has been demonstrated that microwave mediation could be combined with the efforts of solid-supported chemistry to enable the development of novel pathways in organic synthesis. 

The recent interest in organic solid phase synthesis, triggered by the advent of chemical combinatorial methods (1-7), also accelerated methodology development. Simplification of chemical protocols, their robustness, and amenability to handling large arrays of compounds, prepared by combinatorial/ parallel solid phase synthesis, is one area that witnessed numerous novel contributions. This chapter describes an apparatus and method for gaseous cleavage of compounds from solid phase supports. 

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