17241-10-0Relevant articles and documents
Trithioorthoester Exchange and Metathesis: New Tools for Dynamic Covalent Chemistry
Bothe, Michael,Furlan, Ricardo L. E.,Orrillo, A. Gastón,Von Delius, Max
, p. 1988 - 1994 (2019/10/22)
To expand the toolbox of dynamic covalent and systems chemistry, we investigated the acid-catalyzed exchange reaction of trithioorthoesters with thiols. We found that trithioorthoester exchange occurs readily in various solvents in the presence of stoichiometric amounts of strong Bronsted acids or catalytic amounts of certain Lewis acids. The scope of the exchange reaction was explored with various substrates, and conditions were identified that permit clean metathesis reactions between two different trithioorthoesters. One distinct advantage of S, S, S-orthoester exchange over O, O, O-orthoester exchange is that the exchange reaction can kinetically outcompete hydrolysis, thereby making the process less sensitive to residual moisture. We expect that the relatively high stability of the products might be beneficial in future supramolecular receptors or porous materials.
Sulfonyl esters 7. The second and third sequences in the Trithioorthoformate Reaction
Ginige, Kashyapa Ananda,Goehl, John Edward,Langler, Richard Francis
, p. 1638 - 1648 (2007/10/03)
A previous report has established the intermediacy of a sulfide-sulfonate ester in the one-pot conversion of an aryl mercaptan and a sulfonate ester into the corresponding trithioorthoformate. This report describes evidence for the sequential intermediacy of a bissulfide-sulfonate ester and a dithiosulfene in the conversion of the sulfide-sulfonate ester into the trithioorthoformate. A new sulfonate ester is shown to give the highest yield of trithioorthoformate.
SN2 Deprotection of Synthetic Peptides with a Low Concentration of HF in Dimethyl Sulfide: Evidence and Application in Peptide Synthesis
Tam, James P.,Heath, William F.,Merrifield, R. B.
, p. 6442 - 6455 (2007/10/02)
An SN2 deprotection reaction for synthetic peptides was observed when the weak base dimethyl sulfide was used as a diluent for HF.Kinetic studies of the deprotection of O-benzylserine revealed that there was a sharp changeover in mechanism from AAL1 to AAL2 when the concentration of HF in dimethyl sulfide was below 55percent.The changeover in mechanism was also found in the deprotection of O-benzyltyrosine.At higher HF concentrations (>55percent), the AAL1 cleavage mechanism, which generates carbonium ions, led to significant 3-benzyltyrosine side product.However, at low HF concentrations, the side product was minimal as a result of an AAL2 cleavage mechanism in which carbonium ions are not formed.A sharp increase of side product was seen when the HF concentration reached the critical changeover concentration.The HF-dimethyl sulfide reagent was also found to reduce methionine sulfoxide to methionine and, in the presence of a thiol, to deprotect Ni-formyltryptophan to tryptophan.Both of these reactions were also dependent on the concentration of HF and were optimal at low concentrations.Furthermore, deprotection of aspartic and glutamic acid side chain benzyl esters at the low HF concentration also minimized the AAC1 mechanism and the accompanying acylation side reactions.A practical mixture for the SN2 deprotection reaction was found to be HF-dimethyl sulfide-p-cresol (25:65:10 v/v).For the deprotection of Trp(For)-containing peptides, the reagent was adjusted to HF-dimethyl sulfide-p-cresol-p-thiocresol (25:65:7.5:2.5 v/v) so that the Ni-formyl could be removed concomitantly with other protecting groups.The low-acidity function, SN2 reaction was also effective for solid-phase peptide synthesis.The same protecting groups were removed as in solution, and in addition the bond holding the peptide to the resin support was cleaved.For more resistant anchoring bonds and protecting groups a combined low-high HF procedure was developed, in which most of the precursors of harmful carbonium ions are removed by a SN2 mechanism before the final strong-acid, SN1, step begins.The new deprotection procedure was tested on three synthetic model peptides, methionine-enkephalin, bovine growth hormone fragment (128-131), and C-terminal pentagastrin amide, and was found to provide efficient deprotection and significant reduction in the level of alkylation side reactions, the rearrangement to aspartimide, and the acylation of aromatic scavengers by glutamic acid.
