Organic & Biomolecular Chemistry最新文献

The Sonogashira cross-coupling of 2-bromo-3,3-difluoroallyl benzyl sulfide with various terminal acetylenes afforded the corresponding 2-(difluoromethylene)but-3-yn-1-yl benzyl sulfides in acceptable to good yields. Subsequent double iodation of the enyne sulfides in a mixed solvent (CHCl₃/EtOH = 50/1) provided promising 4-(difluoroiodomethyl)-3-iodo-2-substituted thiophenes in good to excellent yields.

We report a 14-step synthesis of a C3-C21 fragment of bastimolides A and B, antimalarial macrocyclic polyketides. A crucial ring-opening reaction of an enol ester epoxide showed previously unexplored reactivity, leading to an asymmetric synthesis of α-haloalkyl esters. The α-haloalkyl ester synthesis was shown to be stereospecific, and provided access to a key α-silyloxyaldehyde to initiate application of configuration-encoded 1,5-polyol synthesis. This strategy established the C11/C15 and C15/C19 remote stereochemical relationships of the bastimolides. The potential of this C3-C21 fragment for coupling to C22-C41 was established using a Mukaiyama aldol reaction with a simple enolsilane.

A method for synthesis of cis-4-hydroxyproline analogs is described. A cis epoxide is converted into a cis-4-hydroxyproline, while the trans epoxide is converted into a ketone or α-aminolactone in the presence of Lewis and Brønsted acids. We propose the divergent chemoselectivity is controlled by H-bonding within the cis epoxide.

The Michaelis-Arbuzov reaction is a widely used method to convert alkyl halides into phosphonates and their derivatives, which are valuable organic molecules. The alcohol-based Michaelis-Arbuzov reaction acts as an appealing approach with a variety of advantages. We report herein the metal-free phosphorylation of indol-3-yl methanol substrates promoted by 1,1,1,3,3,3-hexafluoroisopropanol (HFIP). The reaction demonstrates a wide substrate scope and functional group tolerance and also displays powerful generality for the synthesis of (indol-3-yl)methyl phosphonates. Mechanistically, HFIP serves as both an acid to promote dehydration and a nucleophile to progress the phosphonate-forming step.

We have developed a simple and efficient protocol for the chemoselective synthesis of 5-substituted oxazoles via oxidative annulation of substituted acetophenones with NH₄OAc and DMSO using PIDA as an effective oxidant. NH₄OAc and DMSO act as less toxic one nitrogen and one carbon synthons, respectively. It is a metal-free, step and atom economical approach with good functional group tolerance and chemoselectivity.

The deoxygenation of alcohols is an important and extensively studied research area in modern organic chemistry. However, a chemoselective and clean method is still required for large-scale biochemical production. Herein, we report a strategy for the deoxygenation of alcohols into alkanes using polymethylsiloxane (PMHS) as the reductant with the assistance of iodide. This method, which does not require a metal catalyst, furnishes 5-methylfurfural in 99% yield from hydroxymethylfurfural within 2 h at 140 °C and tolerated a broad scope of functional groups, including phenyl, furanyl, naphthyl, thienyl and allyl alcohol derivatives. A kinetic study revealed that cleavage of the C-I bond formed by the substitution of the hydroxyl group by iodide is the rate-determining step. A mechanistic study suggested a radical mechanism for this alcohol deoxygenation reaction.

There are myriad [2]catenanes and [2]rotaxanes that consist of two interlocked molecular components. On occasion, supramolecular chemists prepare interlocked molecules where there are covalent linkages between the interlocked molecular components. In this review, progress on pretzelanes ([1]catenanes), [1]rotaxanes and molecular figures-of-eight is surveyed. Particular attention is paid to the application of such molecules, especially where the interlocked structure and/or the covalent linkage(s) play a key functional role.

The development of synthetic receptors capable of selectively binding and transporting saccharides is crucial but highly challenging. In this study, two foldameric receptors 1 and 2, consisting of two repeating monomers, indolocarbazole and naphthyridine units, with different aromatic spacers in the middle of their sequences, have been synthesised. These receptors fold into helical conformations, and the two strands of each receptor are assembled to create domain-swapping cavities for binding monosaccharides by multiple hydrogen bonds. According to ¹H NMR, CD spectroscopy, mass spectrometry, and ITC experiments, receptor 1 forms two distinct 2 : 2 complexes with methyl β-D-galactopyranoside and methyl β-D-glucopyranoside: (1-MM)₂⊃(methyl β-D-galactopyranoside·2H₂O)₂ and (1-MP)₂⊃(methyl β-D-glucopyranoside)₂. Despite being composed of identical foldamer strands, these two complexes exhibit notably different folding and assembly modes to achieve optimal stability. The binding affinities of 1 for methyl β-D-galactopyranoside and methyl β-D-glucopyranoside are estimated to be log K = 12.7 and 13.3, respectively, in 5% (v/v) DMSO/CH₂Cl₂. On the other hand, receptor 2 forms a stable 2 : 2 receptor/guest complex with methyl β-D-glucopyranoside, (2-MP)₂⊃(methyl β-D-glucopyranoside)₂, with an association constant of log K = 13.9, which is significantly higher than that of methyl β-D-galactopyranoside (log K = 11.1) and methyl α-D-glucopyranoside (log K = 10.6). Furthermore, receptor 2 facilitates the selective transport of methyl β-D-glucopyranoside over other glycosides across an organic phase (CH₂Cl₂) in U-tube experiments.

Bridged bicyclo[3.3.1]nonanes having the O,O-ketal subunit are widely found in medicinal compounds. While several acid-catalyzed approaches have been reported for the construction of ketals, this study discloses an imidazole-catalyzed modular construction of bicyclo[3.3.1]nonanes from naphthols/phenols and 3-acyl-2-hydroxyl chromenes. The proposed reaction pathway follows a formal [3 + 3] cycloaddition of phenols and an oxonium dipolar intermediate. The reaction is efficient regarding scalability, environmentally benign conditions, and resulting in the products in good to excellent yields.

Racemic assembly of minimalistic heterochiral tripeptides boosts their biocatalytic activity for ester hydrolysis. The amino acidic sequences are bioinspired and feature histidine (His) as a catalytically active residue, and the diphenylalanine (Phe-Phe) motif to drive self-assembly into anisotropic nanostructures that gel. This study thus provides key insights for the design of green biocatalysts with improved activity.