α‐Substitution Effects on the Ease of S→N‐Acyl Transfer in Aminothioesters

Abstract

In S-acylcysteines and homocysteines, the efficacy and rate of S→N-acyl transfer (5 and 6 cyclic TSs) vary with the size of S-acyl group. Conformational and quantum chemical calculations indicate that the spatial distance, b(N-C), between the terminal amine and the thioester carbon is shortened by α-C(O)X (X = OH, OMe, NH2 ) substituents.

Development and Characterization of a Potent Free Fatty Acid Receptor 1 (FFA1) Fluorescent Tracer

“…The fluorescent tracer molecules 2 and 4 were synthesized by similar strategies. Tracer 2 was synthesized from the previously published alkyne intermediate 6 by alkylation with Boc-protected 2-(2-aminoethoxy)­ethyl tosylate to give 7 , followed by concomitant acid catalyzed ester hydrolysis and Boc-deprotection to give the zwitterionic intermediate that was used directly in the reaction with NBD chloride and purification by preparative HPLC gave 2 in 24% yield from 6 (Scheme ).…”

Long‐Range Chemical Ligation from N→N Acyl Migrations in Tryptophan Peptides via Cyclic Transition States of 10‐ to 18‐Members

“…The lowest energy conformer facilitates N→N acyl transfer due to the formation of an amide bond in the ligated peptide. We applied techniques previously employed27, 35, 36 for similar ligation reactions including a full conformation search followed by scoring of the conformers based on the spatial distances between the reactive termini, b (NC). The full conformation search considered both rotatable bonds and the phenyl ring of twenty‐four related compounds, 9 a to 20 c (including Leu/Val‐containing isopeptides, which were used for prediction purposes), and the analysis was performed by using the MMX force field,37 in PCMODEL v.9.3 software 38.…”

Conformationally Assisted Lactamizations for the Synthesis of Symmetrical and Unsymmetrical Bis-2,5-diketopiperazines

“…In order to evaluate the role of proline in cyclization, we analyzed the spatial distances between relevant reaction centers b (N–C) in disulfides Cbz-Cys-Pro-Bt 4a and Cbz-Cys-Leu-Bt 4d . Computational analysis used previously were employed − for long-range acyl migration reactions including a full conformational search followed by scoring the conformers based on energies and spatial distances between relevant centers b (N–C). To justify the spatial distance b (N–C), quantum chemical calculations were carried out at DFT level of theory , and/SV(P), def2-SV(P) basis sets using TURBOMOLE V5.9, , a development of the University of Karlsruhe and Forschungszentrum Karlsruhe GmbH, 1989–2007, TURBOMOLE GmbH, since 2007; available from .…”