The use of the tert-butyloxycarbonyl (Boc) as the Nα-amino protecting group in peptide synthesis can be advantageous in several cases, such as synthesis of hydrophobic peptides and peptides containing ester and thioester moieties. The primary challenge of using Boc SPPS is the need for treatment of the resin-bound peptide with hazardous hydrogen fluoride (HF), which requires special equipment.
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http://dx.doi.org/10.1007/978-1-62703-544-6_4 | DOI Listing |
Chem Biol Drug Des
January 2025
Department of Molecular Biology and Biochemistry, University of California, Irvine, California, USA.
A new series of 13 ritonavir-like inhibitors of human drug-metabolizing CYP3A4 was rationally designed to study the R side-group and R end-group interplay when the R side-group is represented by phenyl. Spectral, functional, and structural characterization showed no improvement in the binding affinity and inhibitory potency of R/R-phenyl inhibitors upon elongation and/or fluorination of R-Boc (tert-butyloxycarbonyl) or its replacement with benzenesulfonyl. When R is pyridine, the impact of R-phenyl-to-indole/naphthalene substitution was multidirectional and highly dependent on side-group stereo configuration.
View Article and Find Full Text PDFChemMedChem
December 2024
School of Chemistry, University College Dublin, Dublin, D04 N2E2, Ireland.
Inspired by the cyclopentenone family of prostaglandins, a series of 4-aza, cross-conjugated cyclopentenones is described. Synthesised from N-protected (4R)-aza-cyclopentenone 5, the exocyclic alkene was installed using a modified Baylis-Hillman type aldol reaction, whereby carbon-carbon bond formation is accompanied by dehydration. In this manner octanal and octenal, for example, can be introduced to mimic the ω-group present in the natural prostaglandins.
View Article and Find Full Text PDFJ Chem Phys
December 2024
Department of Chemistry, Indian Institute of Science Education and Research Pune, Dr. Homi Bhabha Road, Pashan, Pune 411008, India.
Herein, we have investigated the effect of microhydration on the secondary structure of a capped dipeptide Boc-DPro-Gly-NHBn-OMe (Boc = tert-butyloxycarbonyl, Bn = Benzyl), i.e., Pro-Gly (PG) with a single H2O molecule using gas-phase laser spectroscopy combined with quantum chemistry calculations.
View Article and Find Full Text PDFOrg Lett
October 2024
Fachbereich Chemie, Philipps-Universität Marburg, Hans-Meerwein-Straße 4, 35043 Marburg, Germany.
A straightforward and general strategy for the catalytic asymmetric synthesis of β-tryptophans by carboxylic-acid-directed intermolecular C-H amination has been developed. The iron-catalyzed C-H amination of 3-indolepropionic acids with BocNHOMs (Boc, -butyloxycarbonyl; OMs, methylsulfonate) in the presence of the base piperidine provides N-Boc-protected β-tryptophans in a single step with high enantiomeric excess (ee) of up to >99%. Mechanistic experiments and density functional theory calculations support a mechanism through carboxylate-directed iron-mediated C(sp)-H nitrene insertion.
View Article and Find Full Text PDFAngew Chem Int Ed Engl
January 2025
Department of Chemistry, Princeton University, Princeton, NJ 08544, USA.
Tryptophan and its non-canonical variants play critical roles in pharmaceutical molecules and various enzymes. Facile access to this privileged class of amino acids from readily available building blocks remains a long-standing challenge. Here, we report a regioselective synthesis of non-canonical tryptophans bearing C4-C7 substituents via Rh-catalyzed annulation between structurally diverse tert-butyloxycarbonyl (Boc)-protected anilines and alkynyl chlorides readily prepared from amino acid building blocks.
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