SPPS of protected peptidyl aminoalkyl amides

Karavoltsos, Manolis; Mourtas, Spyridon; Gatos, Dimitrios; Barlos, Kleomenis

doi:10.1002/psc.421

Cited by 3 publications

(2 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…To address the aforementioned issues, we began to explore alternative approaches for the synthesis of the key phenacyl halide functionality. We postulated that such a functionality could be incorporated using Friedel−Crafts chemistry, and evaluation of the literature showed that the amino phthalimide 11 , accessible from l -phenylalaninol 12 , was a known compound that could serve as a substrate for just such an alternative approach to GSK923295A via the phthalimide intermediate 11 (Figure ).…”

Section: Resultsmentioning

confidence: 99%

Discovery and Development of an Efficient, Scalable, and Robust Route to the Novel CENP-E Inhibitor GSK923295A

Bellingham

Buswell

Choudary

et al. 2010

Org. Process Res. Dev.

View full text Add to dashboard Cite

The discovery and development of an efficient manufacturing route to the CENP-E inhibitor 3-chloro-N-{(1S)-2-[(N,Ndimethylglycyl)amino]-1-[(4-{8-[(1S)-1-hydroxyethyl]imidazo[1,2-a]pyridin-2-yl}phenyl)methyl]ethyl}-4-[(1-methylethyl)oxy]benzamide (GSK923295A) is described. The existing route to GSK923295A was expensive, nonrobust, used nonideal reagents, and consistently struggled to deliver the API needed for clinical studies. The new synthesis commences from the readily available L-phenylalaninol, which is smoothly converted through to GSK923295A using key Friedel-Crafts acylation as well as selective acylation chemistries. Downstream chemistry to GSK923295A is both high yielding and robust, and the resulting process has been demonstrated first on the kilo scale and subsequently in the pilot plant where 55 kg was successfully prepared. The resulting process is simple, uses cheaper raw materials, is greener in that it avoids using aluminum, tin, and bromination chemistries, and obviates the need for chromatographic purification. Also discussed are the route derived impurities, how they were unambiguously prepared to confirm structure and processing amendments to control their formation, and enhancements to the new process to facilitate future processing.

show abstract

Section: Resultsmentioning

confidence: 99%

Discovery and Development of an Efficient, Scalable, and Robust Route to the Novel CENP-E Inhibitor GSK923295A

Bellingham

Buswell

Choudary

et al. 2010

Org. Process Res. Dev.

View full text Add to dashboard Cite

show abstract

“…The approach that we introduce here [2] involves the use of a 2-chlorotrityl chloride (CTC) resin, a polymer support functionalized with chlorotrityl groups. These groups graft nucleophiles, such as thiols, [12] amines [13] and carboxylates, [14] allowing cleavage of the final product under mild acidic conditions. In addition, this resin has the advantage that it can be regenerated several times, [15] a fact supported by other studies by our group.…”

Section: Introductionmentioning

confidence: 99%

Effective and Versatile Strategy for the Total Solid‐Phase Synthesis of Alkanethiols for Biological Applications

et al. 2013

View full text Add to dashboard Cite

Biological applications increasingly demand tailored surfaces with a range of functional groups. Herein we describe a straightforward and inexpensive method based exclusively on solid‐phase synthesis for the preparation of a variety of customized alkanethiols (ATs). The technique overcomes all the difficulties encountered during the preparation of these molecules in solution. The procedure allows the use of ATs without further purification for the preparation of self‐assembled monolayers on gold, typically used to achieve functional group diversity on this surface.

show abstract