Organic & Biomolecular Chemistry最新文献

We report an azothiazole-based probe as a chemosensor for urea with a LOD of 45 μM. The underlying sensing principle is an instantaneous color change associated with the complex forming between the probe and ammonia, a hydrolysis product of urea catalyzed by the enzyme urease. In addition, the probe has a broad scope in sensing biologically significant amines such as arginine and lysine across a wide range of pH (4 to 8). Through extensive spectroscopic and computational studies in conjunction with control experiments, the importance of H-bonding in the sensing mechanism has been unraveled, revealing the stoichiometry, binding constant and LOD of these analytes with the probe. Indeed, the two individual amino acids can be distinguished by the spectral changes associated with UV-vis spectroscopy or by contrasting color diffusion under agarose gel conditions. Moreover, the probe shows a broad scope in detecting a range of aliphatic primary and secondary amines, including cyclic amines. The utility of the probe has also been demonstrated by using it for sensing urea in urine samples. These attributes make this probe a cost-effective, reusable and versatile chemosensor with ease of handling for sensing multianalytes by varying the conditions and detection modes.

Arylation of C1-H bonds in pyrrolo[1,2-a]quinoxaline derivatives has hitherto been challenging. The sole method known until now suffers from a narrow scope of aryl iodides, while requiring an overstoichiometric amount of a silver additive and a high-molecular-weight phosphine ligand. Herein, we developed a method for coupling C1-H bonds in pyrrolo[1,2-a]quinoxalines with aryl bromides in the presence of simple reagents, namely Pd(OAc)₂ as catalyst, PPh₃ as ligand, K₂CO₃ as base, and 1,4-dioxane as solvent. This successful arylation did not require any silver additive and was tolerant of a wide range of functional groups such as aldehyde, nitro, cyano, ester, and heterocycles.

In this paper, a new asymmetric total synthesis of optically pure (+)-trichostatin A (1a) is described via a route that utilises a Marshall chiral allenylzinc addition between 9 and 4-dimethylaminobenzaldehyde (10) and an O-depivaloylation at its early stages. O-Directed free radical hydrostannation of the resulting propargylic alcohol 15 with Ph₃SnH/cat. Et₃B/O₂ in PhMe at rt thereafter provided the (Z)-α-triphenylstannylvinyltin 16 in 80-89% yield, with complete stereocontrol and very high α : β regioselectivity (25 : 1). A stereoretentive I-Sn exchange reaction between 16 and I₂ (1.4 equiv.) in CH₂Cl₂ (-78 °C to rt, 1 h) subsequently secured the vinyl iodide 18 in 84-96% yield. The latter was transformed into the enal 4 by successive TPAP/NMO (Ley-Griffith) oxidation and a high yielding (80%) Stille reaction between the α-iodo enal 20 and Me₄Sn, catalysed by Pd(PPh₃)₄ in DMF at 60 °C, under the Baldwin-Lee conditions, which use CsF and CuI as promoters. A Wittig reaction between 4 and Ph₃PCHCO₂Et (5), saponification, and DDQ oxidation next afforded (+)-trichostatic acid (22). Helquist's ethyl chloroformate mixed-anhydride/TBSONH₂ coupling procedure (ref. 17e) thereafter secured (+)-trichostatin A (1a) in good yield. This new total synthesis of 1a is the first-ever successful application of the O-directed dialkylacetylene free radical hydrostannation with Ph₃SnH/cat. Et₃B/O₂ in a dialkylaniline N-containing disubstituted alkynol system, and it now provides a convenient means of accessing many novel trichostatin analogues for future biological screening.

The rhodium(III)-catalyzed asymmetric allylic cyclization of cyclohexadienone-tethered allenes is successfully developed. This protocol exhibits broad functional group tolerance and is applicable for modifying biologically active molecules containing phenol structures. Notably, compounds 3ga and 3ha demonstrate promising anticancer properties.

Fmoc-protected β-hydroxyasparagine is an essential structural motif in organic chemistry, widely present in natural products and clinically important drugs, such as antibiotics. Here, a diastereoselective synthesis of Fmoc-protected HOAsn from a simple Garner's aldehyde has been developed. The Fmoc protected Garner's aldehyde reacted with triphenylmethyl isocyanide and formic acid at 60 °C, affording good yield with excellent diastereoselectivity. The application of the Passerini reaction product Fmoc-protected HOAsn for Fmoc-SPPS towards the synthesis of nicrophorusamide A and its analogues has also been reported, which is conducive to systematic SAR studies.

Photoinduced C-H functionalization of quinoxalines is a key transformation for the derivatization of biologically relevant molecules. Traditionally, homogeneous catalysts such as transition metal complexes or organic dyes are indispensable for these transformations. However, these methods often suffer from limitations related to cost, recyclability, and environmental impact. Herein, by using inexpensive, readily available and recyclable graphitic carbon nitride (g-C₃N₄) as a heterogeneous photocatalyst, a diverse range of acyl- and trifluoromethyl-functionalized quinoxalinone derivatives were synthesized in good to excellent yields under the irradiation of blue LEDs. Control experiments confirmed that the photogenerated electrons played a pivotal role in promoting the generation of acyl and trifluoromethyl radical intermediates. Moreover, g-C₃N₄ showed no significant loss of activity after at least six reaction cycles. Potentially, g-C₃N₄ represents a promising alternative to noble metal photocatalysts in organic synthesis.

Developing innovative approaches for the synthesis of compounds that integrate imidazo[1,2-a]pyridines and fluoro fragments is crucial. Herein, an expedient [3 + 3] annulation method for synthesizing ring-fluorinated imidazo[1,2-a]pyridines via two consecutive C-F substitutions from readily available 1C,3N-dinucleophiles and β-CF₃-1,3-enynes is presented. This protocol exhibits several appealing features, including readily available and inexpensive substrates, a broad range of functional groups, step and atom economy, and mild reaction conditions without any transition-metal catalysts.

Aerobic oxidation of benzyl alcohols to aromatic aldehydes and aromatic esters is an important chemical transformation. Here, sodium trifluoromethanesulfinate was used as the precursor of an organic photocatalyst, and it transformed into pentacoordinate sulfide under an O₂ atmosphere and light irradiation at room temperature. The in situ formed pentacoordinate sulfide showed excellent photocatalytic efficiency, with photocatalytic aerobic oxidation of benzyl alcohols providing aromatic aldehydes in good yields; photocatalytic aerobic oxidation of benzyl alcohols in other aliphatic alcohols afforded aromatic esters in moderate to good yields. The method avoids the use of precious transition-metal complexes and elaborate organic dyes as photocatalysts.

This article describes concise and practical synthetic approaches toward the multigram-scale preparation of value-added conformationally constrained 5-spirocyclic α-prolines from readily accessible starting materials. Direct carboxylation of 2-spiropyrrolidines is a novel and promising approach to achieve this goal, particularly for substrates with no acidic centers within the spiro-linked portion of the pyrrolidine core. The method allows for quick, one-step preparation of the target chemicals in good yields. An alternative synthetic avenue was designed for substrates unsuitable for direct carboxylation. This 4-step protocol involves common laboratory practice transformations and is comparable in its efficiency to the carboxylation method. This study concludes a series of our investigations on the elaboration of efficient methods for the construction of spiro-proline frameworks.

Multi-functionalized carbon chains are prevalent motifs existing in various natural products and drugs. How to construct multi-functionalized carbon chains represents a meaningful task. Herein, we developed a photo-induced stereoselective 1,4-carbosulfonylation of butadiene to construct multi-functionalized carbon chains under nickel catalysis. A wide variety of aryl iodides and sodium sulfinates could be facilely coupled with butadiene to generate difunctionalized olefin intermediates. Taking advantage of the internal CC bond, various functional groups have been efficiently incorporated to construct multi-functionalized aliphatic compounds. A scale-up reaction, an iterative reaction and late-stage modifications have been performed to further demonstrate the synthetic utility of this protocol.