Current Organic Synthesis - Volume 19, Issue 7, 2022

Background and Objective: Residues from shrimp farming have a great potential for sugar production and the production of derivatives for the low-carbon chemical industry. Obtainment of bioactives from chitosan has been extensively investigated using different methodologies. The purpose of this work was to study the chitosan depolymerization reaction aiming at the production of monomers without the use of additional enzymes or mineral acids. Materials and Methods: In this work, we systematically study the effect of sodium nitrite concentration and reaction conditions (pH and temperature ranges) with acetic acid as the solvent on the chitosan depolymerization reaction aiming at the production of monomers, specifically 2,5- anhydromannose, without the use of additional enzymes or mineral acids. Results: The results indicate that only a small range of reaction conditions and nitrite concentrations allow for obtaining the monomer, while in most combinations of these parameters, oligomers are obtained. We found that the temperature decisively affects the reaction yield, with the attainment of 2,5-anhydromannose favored at lower temperatures. Conclusion: The method proved to be simple and easy to perform allowing to obtain 2,5- anhydromannose with the use of low-cost reagents. This monomer can be converted into several derivatives for industrial application (5-Hydroxymethylfurfural, ethanol, etc.)

There has been a growing body of studies on benzothiazoles and benzothiazole derivatives as strong and effective anti-tumor agents against lung, liver, pancreas, breast, and brain tumors. Due to the highly proliferative nature of the tumor cells, the oxygen levels get lower than that of normal tissues in the tumor microenvironment. This situation is called hypoxia and has been associated with increased ability for carcinogenesis. For the drug design and development strategies, the hypoxic nature of the tumor tissues has been exploited more aggressively. Hypoxia itself acts as a signal initiating system to activate the pathways that eventually lead to the spread of the tumor cells into the different tissues, increases the rate of DNA damage, and eventually ends up with more mutation levels that may increase the drug resistance. As one of the major mediators of hypoxic response, hypoxia-inducible factors (HIFs) have been shown to activate angiogenesis, metastasis, apoptosis resistance, and many other protumorigenic responses in cancer development. In the current review, we will be discussing the design, synthesis, and structureactivity relationships of benzothiazole derivatives against hypoxic tumors such as lung, liver, pancreas, breast, and brain as potential anti-cancer drug candidates. The focus points of the study will be the biology behind carcinogenesis and how hypoxia contributes to the process, recent studies on benzothiazole and its derivatives as anti-cancer agents against hypoxic cancers, conclusions, and future perspectives. We believe that this review will be useful for researchers in the field of drug design during their studies to generate novel benzothiazole-containing hybrids against hypoxic tumors with higher efficacies.

A broad range of N-sulfonyformamidines, widely used intermediates for drugs, were synthesized in moderate to excellent yields from 2-Pyridinemethanamine as N-source via Coppercatalyzed C-N cleavage. Firstly, N-(2-pyridinylmethyl)benzenesulfonamides were smoothly synthesized via 2-pyridinemethanamine and sulfonyl chlorides, then reacted with N,Ndimethylformamide dimethyl acetal to obtain the corresponding N-Sulfonylformamidines analogs, during which pyridin-2-ylmethyl and sulfonyl groups were essential for the C-N bond cleavage. The current work presents a valuable complementarity to the synthesis of N-sulfonyformamidines as 2- pyridinemethanamine can provide the N source and sulfonyl chloride,s which could be original materials. Background: N-sulfonylamidines have gained considerable attention from schools and industries because of their unique bioactivity. Since Pinner’s strategy, expanding the synthesis methods of Nsulfonylamidines has been the goal of many organic chemists over the past decades. Besides the crash reaction conditions and the participation of undesirable reagents, the production of Nsulfonylamidines commonly required unstable ammonia and azides as the source of nitrogen that hindered the further development and application of N-sulfonylamidine derivatives. Objective: The study aims to find a stable N source to replace NaN3 or NH3 to synthesize N-sulfonylamidines from sulfonyl chlorides. Methods: Firstly, N-(2-pyridinylmethyl)benzenesulfonamides were smoothly synthesized via 2- pyridinemethanamine and sulfonyl chlorides. Then the reaction conditions of N-(2-pyridinylmethyl) benzenesulfonamides and N,N-dimethylformamide dimethyl acetal (DMF-DMA) were screened and optimized. The reaction was processed in glycol at 80 132;ƒ for 8 hours with the addition of 5 mol% Cu(OAc)2·H2O as a catalyst. Results: Taking advantage of pyridin-2-ylmethyl, a scope of N-Sulfonylformamidines were synthesized from those N-(2-pyridinylmethyl)benzenesulfonamides under copper-catalyzed C-N bond cleavage. Conclusion: This ready synthetic method will be more of a promising inspiration for bioactive compound synthesis and drug development than for an innovative approach to synthesizing N-sulfonylformamidines.

Background: Due to the increasing chemical and biological threats posed by terrorist attacks, there is a need to design and prepare nanofibers (NFs) with the ability to neutralize CWAs. For this purpose polyacrylonitrile NFs and polyoxomolybdate [Mo154] (abbreviated as PAN NFs/[Mo154]) as a heterogeneous catalyst was prepared by electrospinning method with a diameter of about 100nm. Objective: The PAN NFs/[Mo154] catalyze the selective aerobic oxidation of sulfur mustard stimulants, such as 2-chloroethyl ethyl sulfide (2-CEES) and 2-chloroethyl phenyl sulfide (2-CEPS) under green and “ambient” conditions (25 °C, 1atm O2) in the presence of ethanol with high efficiency and selectivity. 2-CEES was selected as a model reaction to optimize the parameters of the reaction. Methods: The progress of the reaction was evaluated after different times using GC-FID, GCMS and TLC. The reaction product was also confirmed by ¹H-NMR spectroscopy. Results: The aerobic oxidation results of 2-CEES showed that PAN NFs/[Mo154] have a conversion of 98% to produce only a nontoxic product, 2-CEESO with the selectivity of 100% after 45min. The results were performed using [Mo154] without any PAN NFs for comparison whereas [Mo154] converts only 52% of 2-CEES under identical conditions. Conclusion: Heterogeneous PAN NFs/[Mo154] catalyst was reused after washing with solvent up to 5 steps without leaching of [Mo154] from PAN NFs and without any loss in efficiency due to the morphology of NFs. In addition to the recovery of PAN NFs/[Mo154] in different cycles, the use of FT-IR, UV-Vis and TEM techniques confirms the stability and morphology of PAN NFs/[Mo154] after the fifth cycle, 2-CEES oxidation. According to our information, this report is the first use of PAN NFs enriched with [Mo154] for aerobic oxidation of sulfur mustard simulants.

Aim and Objective: Benzoxazoles are of great importance in natural products, pharmaceutical agents as well as synthetic intermediates. Although many works on the construction of benzoxazoles by Cu-catalyzed intramolecular O-arylation of ortho-haloanilides have been reported, only a few reports about transition metal-catalyzed synthesis of benzoxazoles from inactive 2-chloroanilides so far. This work aimed to explore a green and cheap protocol for intramolecular O-arylation of inactive 2-chloroanilides to prepare 2-arylbenzoxazoles. Materials and Methods: We found that Cu(acac)2/1,10-Phen complex was beneficial to intramolecular O-arylation of 2-chloroanilides using K2CO3 as a base in EtOH at 90 °C to prepare benzoxazoles. Results: An efficient and green method was developed for Cu(II)-catalyzed intramolecular Oarylation of inactive 2-chloroanilides. Conclusion: In this way, many 2-arylbenzoxazoles were prepared in good yields.

Aims: A simple, transition-metal-free C-S coupling protocol for the synthesis of aryl thioethers is reported. Background: Sulfur-containing moieties are ubiquitous in pharmaceutical drugs and materials and therefore methods for their construction are of great importance. One approach entails the catalytic coupling of an aryl halohydrocarbon with a thiol, but the transition metal catalysts usually used are prone to poisoning by participating sulfur species and efficient catalysis is usually only achieved after complex ligand optimization. Objective: New transition-metal-free approaches to the synthesis of C-S bonds are urgently need. Methods: We screened the reaction conditions such as alkali, crown ether, solvent, temperature, etc., tested the compatibility of the reaction substrate, and analyzed the mechanism process. Results: The optimized reaction conditions were determined to be 1.0 equiv of aryl halides and 1.2 equiv of thiols at 110 132;ƒ in toluene with K2CO3 (1.5 equiv) as a base, promoted by 10 mol% dicyclohexano-18-crown-6. Up to 33 examples of thioethers were synthesized under transitionmetal- free conditions in good to excellent yields. Conclusion: We have developed a simple and efficient method for the C-S cross-coupling of a wide variety of (hetero)aryl halides and thiols mediated by dicyclohexano-18-crown-6 and without the need for transition-metal catalyst. In addition, the preparation and gram-scale experiments of a variety of drug molecules further verify the practicability of our developed method.

Aims and Objective: The syntheses of glucuronide metabolites of phenolic xenoestrogens triclosan and 2-phenylphenol, namely triclosan-O-glucuronide (TCS-G; 1), and 2-phenylphenol-Oglucuronide (OPP-G; 2), were achieved for use as analytical standards. Methods: Under classical conditions previously reported for glucuronide synthesis, the final basic hydrolysis of the peracylated ester intermediate leading to the free glucuronides is often a limiting step. Indeed, the presence of contaminating by-products resulting from ester elimination has often been observed during this step. This is particularly relevant when the sugar unit is close to a crowded environment as for triclosan and 2-phenylphenol. Results: To circumvent these problems, we proposed mild conditions for the deprotection of peracetylated glucuronate intermediates. Conclusion: A new methodology using a key imidate following a two-step protocol for acetates and methyl ester hydrolysis was successfully applied to the preparation of TCS-d3 (1) and OPP-G (2) as well as deuterated isotopomers TCS-d3-G (1-d3) and OPP-d5-G (2-d5).