Peptide Ligation–Desulfurization Chemistry at Arginine

The utility of a new β‐thiol arginine building block in ligation–desulfurization chemistry has been demonstrated through reactions and kinetic studies with a range of peptide thioesters. Application of the method is highlighted by a one‐pot, kinetically controlled, rapid ligation to generate a 7 kDa MUC1 glycopeptide

Synthesis of Gallinamide A Analogues as Potent Falcipain Inhibitors and Antimalarials

Analogues of the natural product gallinamide A were prepared to elucidate novel inhibitors of the falcipain cysteine proteases. Analogues exhibited potent inhibition of falcipain-2 (FP-2) and falcipain-3 (FP-3) and of the development of Plasmodium falciparum in vitro. Several compounds were equipotent to chloroquine as inhibitors of the 3D7 strain of P. falciparum and maintained potent activity against the chloroquine-resistant Dd2 parasite. These compounds serve as promising leads for the development of novel antimalarial agents

Asymmetric aldol reaction using boron enolates

The protocol for the preparation of boron enolates and their subsequent reaction with aldehydes is described, providing convenient access to b-hydroxy ketones in good yields and with high stereoselectivities. The reaction consists of three steps; firstly the ketone is rapidly converted to the corresponding boron enolate, by exposure to a chlorodialkylborane and tertiary amine base, which is then reacted <i>in situ</i> with the aldehyde. Finally, oxidative workup of the resultant boron aldolate provides aldol adduct. The reaction procedure requires approximately 28 h to complete over a two day period, consisting of 5 h to set up the reaction, whereupon the reaction mixture is left at –20 °C overnight (16 h), followed by 7 h for workup and purification

Total Synthesis of Fellutamide B and Deoxy-Fellutamides B, C, and D

The total syntheses of the marine-derived lipopeptide natural product fellutamide B and deoxy-fellutamides B, C, and D are reported. These compounds were accessed through a novel solid-phase synthetic strategy using Weinreb amide-derived resin. As part of the synthesis, a new enantioselective route to (3R)-hydroxy lauric acid was developed utilizing a Brown allylation reaction followed by an oxidative cleavage-oxidation sequence as the key steps. The activity of these natural products, and natural product analogues was also assessed against Mycobacterium tuberculosis in vitro

Total Synthesis of Fellutamide B and Deoxy-Fellutamides B, C, and D

The total syntheses of the marine-derived lipopeptide natural product fellutamide B and deoxy-fellutamides B, C, and D are reported. These compounds were accessed through a novel solid-phase synthetic strategy using Weinreb amide-derived resin. As part of the synthesis, a new enantioselective route to (3R)-hydroxy lauric acid was developed utilizing a Brown allylation reaction followed by an oxidative cleavage-oxidation sequence as the key steps. The activity of these natural products, and natural product analogues was also assessed against Mycobacterium tuberculosis in vitro

One-Pot Peptide Ligation–Desulfurization at Glutamate

An efficient methodology for ligation at glutamate (Glu) is described. A γ-thiol-Glu building block was accessed in only three steps from protected glutamic acid and could be incorporated at the N-terminus of peptides. The application of these peptides in one-pot ligation–desulfurization chemistry is demonstrated with a range of peptide thioesters, and the utility of this methodology is highlighted through the synthesis of the osteoporosis peptide drug teriparatide (Forteo)

Inhibitors of an essential mycobacterial cell wall lipase (Rv3802c) as tuberculosis drug leads

The first targeted inhibitors of an essential M. tuberculosis cell wall lipase, Rv3802c, are described. Lead compounds exhibited nanomolar inhibition of the enzyme, and encouraging antibacterial activity against M. tuberculosis in vitro, supporting Rv3802c as a novel TB drug target

One-Pot Peptide Ligation–Desulfurization at Glutamate

An efficient methodology for ligation at glutamate (Glu) is described. A γ-thiol-Glu building block was accessed in only three steps from protected glutamic acid and could be incorporated at the N-terminus of peptides. The application of these peptides in one-pot ligation–desulfurization chemistry is demonstrated with a range of peptide thioesters, and the utility of this methodology is highlighted through the synthesis of the osteoporosis peptide drug teriparatide (Forteo)

Hydrogen-adduction to open-shell graphene fragments: spectroscopy, thermochemistry and astrochemistry

We apply a combination of state-of-the-art experimental and quantum-chemical methods to elucidate the electronic and chemical energetics of hydrogen adduction to a model open-shell graphene fragment. The lowest-energy adduct, 1H-phenalene, is determined to have a bond dissociation energy of 258.1 kJ mol(–1), while other isomers exhibit reduced or in some cases negative bond dissociation energies, the metastable species being bound by the emergence of a conical intersection along the high-symmetry dissociation coordinate. The gas-phase excitation spectrum of 1H-phenalene and its radical cation are recorded using laser spectroscopy coupled to mass-spectrometry. Several electronically excited states of both species are observed, allowing the determination of the excited-state bond dissociation energy. The ionization energy of 1H-phenalene is determined to be 7.449(17) eV, consistent with high-level W1X-2 calculations