Retro-Mass Spectral Degradation

A target may resist hydrolysis or chemical degradation, or the degradation products may not yield useful information. It is also common that insufficient material exists for proper analysis. In these cases, an alternative degradation technique is available that uses the ionizing electron beam of a mass spectrometer. The ionization pathways available from electron impact in the mass spectmm are bond fission processes that occur by known and predictable pathways. Indeed, each pathway usually follows analogous chemical reaction pathways in a retro-synthetic manner. It therefore follows that an examination of mass spectral ionization patterns can give clues for suitable disconnections and a synthetic tree. 

This basic premise was outlined by Kametani and Fukumoto and used for the synthesis of a number of important alkaloids. As mentioned, the key feature of the analysis is the fact that many chemical reactions appear as their retro analog in the mass spectrum. These retro reactions are disconnections that can be translated directly to a synthetic tree. Some examples of retroreactions that have been identified in the mass 

Wagner-Meerwein (sec. 12.2.B),i 72,178 and (4) a retro-Ritter reaction.It is noted that the Ritter reaction 0 couples and alkene and a nitrile to give an amide. 

In 1963 Merrifield introduced solid-state synthesis for the synthesis of peptides. This technique involves chemical functionalization of a polystyrene bead that reacts with the carboxylic acid portion of a N-protected amino acid to give a polymer-bound amino ester such as 284. When 284 is treated with a reagent to deprotect the amine, it can react with another N-protected amino acid, activated at the carbonyl, to give a dipeptide. This procedure can be repeated to generate the desired polypeptide, and when the target has been attained a reagent is added to cleave the polypeptide from the bead (usually by hydrolysis). This solid-state synthesis can be applied to other types of chemical transformations.  

One problem that must be addressed is chemical reactivity. If a bead reacts with many different reactants (n coupling partners), there will be n products, which is also a problem in solution combinatorial synthesis. Indi-vidual substances can be obtained by fast parallel syntheses, that is, n substances are synthesized in n reaction vessels. = Since it is reasonable that some reactants will react faster and in higher yields than others, 

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