protective groups in organic synthesis greene pdf download
With Lhasa (logic and heuristics applied to synthetic analysis), Corey had invented the first ever computer program for retrosynthesis. Lhasa contained the rules for more than 600 reactions, hand-written by chemists in over 30,000 lines of Fortran code. But what the program was missing was knowledge of protecting groups.
But it was clear that the knowledge on protective groups Greene had amassed within her thesis would be of great value to chemists, far beyond its immediate application to Lhasa. With the help of her husband and a common friend, University of Delaware chemist James Moore, she started cutting down and editing the extensive thesis.
Abstract:The appearance of selenium in organic synthesis is relatively rare, and thus examples in the literature pertaining to the masking of its considerable reactivity are similarly uncommon. Greene's Protecting Groups in Organic Synthesis, the standard reference for the state of the art in this arena, offers no entries for selenium protective methodology, in stark comparison to its mention of the great variety of protecting groups germane to its chalcogen cousin sulfur. This scarcity of Se-protection methods makes it no less interesting and pertinent toward the construction of selenium-containing organic systems which do indeed require the iterative blocking and de-blocking of selenol functionalities. A selenium-containing system which is especially relevant is selenocysteine, as its use in Solid Phase Peptide Synthesis requires extensive protection of its selenol side chain. This review will attempt to summarize the current state of understanding with regard to selenium protection protocol in organic synthesis. Moreover, it will provide a special emphasis on selenocysteine side chain protection, comprising both the breadth of functionality used for this purpose as well as methods of deprotection.Keywords: selenium; selenocysteine; protecting group; protection
We verified also the rapid cleavage of the acetal protections in organic solvents. All the acetals studied were readily removed under the conditions typically applied in oligonucleotide synthesis, i.e., 3% dichloroacetic acid in acetonitrile or in methanol. In most cass the reactions were complete after a couple of minutes. With the trifluoroethyl acetal derivative 4e the reaction was slow enough that the half-life could be measured, and it was shown to be 4 minutes in methanol and 7 minutes in acetonitrile. The polarity of the solvent has a significant effect on the stability. Slower reactions were observed using 3% acetic acid in dioxane, where the half-lives for 4a and 4c were 80 minutes and 5 minutes, respectively. These results indicate that the proposed protecting groups can be applied, for instance, in solution-phase oligonucleotide synthesis without depurination becoming a major problem. Further studies of the applications will be published later.