Organic & Biomolecular Chemistry (v.17, #40)

Front cover (8935-8936).

Contents list (8937-8942).

Natural diterpene pyrones: chemistry and biology by Amjad Ayad Qatran Al-Khdhairawi; Geoffrey A. Cordell; Noel F. Thomas; Narendra Babu Shivanagere Nagojappa; Jean-Frédéric F. Weber (8943-8957).
Diterpene pyrones (DTPs) are a group of well-known, mainly fungal, natural products, first isolated in 1966. As the name indicates, they are composed of two main structural features: a diterpenyl moiety and a pyrone ring. Various names have been given to this class of metabolites; however, biogenetic evidence indicates that they originate through the same metabolic pathway. Based on their biosynthesis, which leads to differences in their structural architecture, the DTPs can be classified into three main types. In addition to their intriguing chemistry, these compounds demonstrate a wide range of biological activities rendering them a desirable target for total synthesis. To date, sixty-seven DTPs have been isolated from various fungal species, with one example originating from the plant kingdom. This review aims at unifying the classification of these compounds, in addition to presenting a detailed description of their isolation, bioactivities, biosynthesis, and total synthesis.

We reported a new method that visible light along with cercosporin, one of the naturally occurring perylenequinonoid pigments with excellent properties of photosensitization, photocatalyzed sp3 (C–H) activation for the synthesis of pyrrolo[3,4-c]quinolones through the annulation of anilines and maleimides under mild conditions.

Construction of indazolo[3,2-a]isoquinolines via [3 + 2] cycloaddition of benzynes by Yue-Kun Li; Ming-Xin Cui; Feng Sha; Qiong Li; Xin-Yan Wu (8963-8968).
A [3 + 2] annulation protocol for the construction of N-substituted indazolo[3,2-a]isoquinolines starting from benzynes and C,N-cyclic azomethine imines was developed. A diverse range of highly functionalized products indazolo[3,2-a]isoquinolines featuring an indazole scaffold can be easily accessed via a one-step reaction under mild conditions, and they show good anti-proliferative activity on cancer cells.

Palladium(ii) ligated with a selenated (Se, CNHC, N)-type pincer ligand: an efficient catalyst for Mizoroki–Heck and Suzuki–Miyaura coupling in water by Kamal Nayan Sharma; Naveen Satrawala; Avinash Kumar Srivastava; Munsaf Ali; Raj Kumar Joshi (8969-8976).
A new 1-[N-benzylacetamido]-3-[1-(2-phenylselenylethyl)]benzimidazolium chloride (L), the precursor of a novel (Se, CNHC, N)-type pincer ligand (L) was synthesised in high yield through a sequence of consecutive reactions of 1H-benzimidazole with ethylene dichloride, sodium selenophenolate, and N-benzyl-2-chloroacetamide. The palladium-promoted reaction of L with PdCl2 resulted in a moisture- and air-insensitive complex [Pd(L–H2Cl)Cl] (1), which demonstrated outstanding catalytic potential for Mizoroki–Heck coupling of aromatic bromides and chlorides (with yields up to 94% and 70%, respectively) at very low catalyst loading (0.2 mol%) and under mild reaction conditions in water. The complex (1) was also investigated for Suzuki–Miyaura coupling and found to be selectively efficient (yields up to 94%) for Suzuki–Miyaura coupling of aromatic bromides at 0.01 mol% of 1 in water. All coupling reactions were carried out in the green and economical solvent, water, which is highly desirable for bulk synthesis of complex molecules in industry. During the catalytic process, complex 1 converted into PdSe nanoparticles (NPs, size range 5–6 nm) in situ. The morphology and composition of these NPs were analysed through high-resolution transmission electron microscopy and transmission electron microscopy-energy dispersive X-ray spectroscopy, respectively. The core-level, X-ray photoelectron spectroscopy analysis confirmed the presence of stable Pd0 and Pd2+ oxidation states in these PdSe NPs. Based on further experimental investigations, these nanoparticles were found to work as a stock of true catalytic species. The hot filtration test, as well as the two-phase test, confirmed the largely homogeneous nature of the catalytic process, which probably proceeds by leaching of solution-phase Pd species from these NPs.

Hypervalent iodane mediated reactions of N-acetyl enamines for the synthesis of oxazoles and imidazoles by Kang Xu; Ruiqi Yang; Shuang Yang; Cheng Jiang; Zhenhua Ding (8977-8981).
A hypervalent iodane reagent used for the intramolecular cyclization of N-acetyl enamines and intermolecular cyclocondensation of enamines and nitriles was investigated. The reaction was performed under mild conditions and gave oxazoles and imidazoles, respectively, in moderate to excellent yields. This transformation exhibits good reactivity, selectivity and functional group tolerance. The selectivity of the intra- or intermolecular reaction is dependent on the structure of N-acetyl enamines.

A facile and regioselective multicomponent synthesis of chiral aryl-1,2-mercaptoamines in water followed by monoamine oxidase (MAO-N) enzymatic resolution by Kate Lauder; Domiziana Masci; Anita Toscani; Aya Al Mekdad; Gary W. Black; Nicola L. Brown; Nicholas J. Turner; Renzo Luisi; Daniele Castagnolo (8982-8986).
A facile microwave assisted three-component protocol allows the synthesis of chiral aryl-1,2-mercaptoamines in water in a few minutes with high yields, bypassing the use of toxic aziridine intermediates. The chiral 1,2-mercaptoamines were then deracemized through enzymatic resolution of the racemates using monoamine oxidase (MAO-N) biocatalysts.

Functionalization of activated methylene C–H bonds with nitroarenes and sulfur for the synthesis of thioamides by Nhan T. Do; Khoa M. Tran; Hao T. Phan; Tuong A. To; Tung T. Nguyen; Nam T. S. Phan (8987-8991).
We report a method to obtain arylthioamides by the functionalization of sp3 C–H bonds in phenylacetic acids and benzyl alcohols. Reactions proceeded without the use of any solvents and were compatible with many functionalities and heterocycles. These conditions allow for a rapid synthesis of thioamides from simple, commercial substrates.

The effect of MR1 ligand glyco-analogues on mucosal-associated invariant T (MAIT) cell activation by Chriselle D. Braganza; Kensuke Shibata; Aisa Fujiwara; Chihiro Motozono; Koh-Hei Sonoda; Sho Yamasaki; Bridget L. Stocker; Mattie S. M. Timmer (8992-9000).
Mucosal-associated invariant T (MAIT) cells are a subset of recently identified innate-like T lymphocytes that appear to play an important role in many pathologies ranging from viral and bacterial infection, to autoimmune disorders and cancer. MAIT cells are activated via the presentation of ligands by MR1 on antigen presenting cells to the MAIT T cell receptor (TCR), however few studies have explored the effects of systematic changes to the ligand structure on MR1 binding and MAIT cell activation. Herein, we report on the first study into the effects of changes to the sugar motif in the known MAIT cell agonists 7-hydroxy-6-methyl-8-d-ribityllumazine (RL-6-Me-7-OH) and 5-(2-oxopropylideneamino)-6-d-ribitylaminouracil (5-OP-RU). Tetramer staining of MAIT cells revealed that the absence of the 2′-hydroxy group on the sugar backbone of lumazines improved MR1–MAIT TCR binding, which could be rationalised using computational docking studies. Although none of the lumazines activated MAIT cells, all 5-OP-RU analogues showed significant MAIT cell activation, with several analogues exhibiting comparable activity to 5-OP-RU. Docking studies with the 5-OP-RU analogues revealed different interactions between the sugar backbone and MR1 and the MAIT TCR compared to those observed for the lumazines and confirmed the importance of the 2′-hydroxy group for ligand binding and activity. Taken together, this information will assist in the development of future potent agonists and antagonists of MAIT cells.

An IBX/NIS-induced intramolecular oxidative annulation of Mannich-type substrates is reported. This metal-free approach involving iodination, NH-oxidation, intramolecular C–N bond formation, and retro-Claisen–Schmidt sequence provides the construction of imidazo[1,2-a]pyridine, imidazo[1,2-a]pyrimidine as well as imidazo[1,2-a]pyrazine frameworks with yields up to 93%. In addition, a sequential one-pot process is also presented.

An efficient synthetic protocol for novel indeno[1,2-a]fluorene derivatives was successfully developed by the base promoted domino reaction of 1,3-indanedione with 3-arylideneindolin-2-ones. The domino reaction in different solvents selectively gave carbamato- or amino-substituted indeno[1,2-a]fluorene in satisfactory yields. Additionally, a similar domino reaction of 1,3-indanediones with chalcones also gave polysubstituted indeno[1,2-a]fluorenes in high yields. The reaction mechanism is believed to proceed with base-promoted dimerization of 1,3-indanedione, Michael condensation, annulation, ring-opening of indolin-2-one and aromatization process.

A mild, efficient and transition-metal free synthetic strategy has been developed for the α-arylation of 4-aminocoumarins. This synthetic strategy proceeds via C(sp2)–C(sp2) bond formation between 4-aminocoumarins and aryne precursors in a single step by simple treatment with a fluoride source in the absence of a metal-catalyst. Moreover, this methodology affords good yields of 4-amino-3-arylcoumarin derivatives bearing halide functionality.

An aminosulfonylation of alkenyl sulfonamides was reported. Using iodine as the catalyst, TBHP as the oxidant, and sulfonyl hydrazides as the sulfonyl radical sources, a variety of sulfonylmethyl piperidines, pyrrolidines and pyrazolines were obtained in moderate to excellent yields.

In this paper, we report the iodine mediated in situ generation of R-Se–I and further its application towards the construction of pyrano[4,3-b]quinolin-1-one derivatives. The structural elaboration of 1-chloro-8-methyl-3-phenylbenzo[b][1,6]naphthyridine 6 was successfully achieved by Sonogashira, Suzuki coupling and dehalogenation reactions. Finally, the synthesized compounds 4a, 5a, 5b, 6, and 7a–7c were studied for photophysical properties including UV-absorption, fluorescence, and quantum yield studies. The synthesized pyranoquinoline derivatives showed λmax, Fmax and Φf values in the range of 391–447 nm, 436–486 nm and 0.004–0.301, respectively in chloroform solvent.

The synthesis of solasodine F-homo-analogues by Urszula Kiełczewska; Jacek W. Morzycki; Lucie Rárová; Agnieszka Wojtkielewicz (9050-9058).
Solasodine derivatives continue to be attractive targets for synthetic chemists due to their interesting biological properties. Herein, we report a concise synthesis of solasodine analogues containing the seven-membered F ring from diosgenin. The key intermediate in the synthesis of 26a-homosolane derivatives was 26-cyanopseudodiosgenin. After reduction of the cyano group, the seven-membered ring was closed with MgBr2·Et2O to yield 26a-homosolanes as a mixture of 22R and 22S epimers. The acylation of the obtained mixture led to the diastereomerically pure 22S N-acylated 26a-homosolasodine derivatives. Moreover, we describe one-step protocol for stereoselective synthesis of 22R-cyanofurostane by treatment of diosgenin with TMSCN/BF3·Et2O.

A water soluble light activated hydrogen sulfide donor induced by an excited state meta effect by Manoranjan Bera; Somnath Maji; Amrita Paul; Souvik Ray; Tapas Kumar Maiti; N. D. Pradeep Singh (9059-9064).
We have utilized an m-amino benzyl based photoremovable protecting group (PRPG) to develop a new water soluble H2S donor. It efficiently releases H2S on demand in a spatio-temporally controlled fashion by an excited state “meta effect” with good chemical and photochemical quantum yield in an aqueous environment. The efficient photorelease of H2S under physiological conditions was also demonstrated by in vitro studies.

The ruthenium-catalyzed meta-selective C–H nitration of various azole ring-substituted arenes by Dong Zhang; Di Gao; Jinlin Cai; Xiaoyu Wu; Hong Qin; Kai Qiao; Chengkou Liu; Zheng Fang; Kai Guo (9065-9069).
The efficient ruthenium-catalyzed meta-selective CAr–H nitration of azole ring substituted arenes has been developed. In this work, Ru3(CO)12 was used as the catalyst, AgNO2 as the nitro source, HPcy3+·BF4 as the ligand, pivalic acid as the additive, and DCE as the solvent, and a wide spectrum of arenes bearing thiazole, pyrazolyl or removable oxazoline directing groups were tolerated in this meta-selective CAr–H nitration, affording the nitrated products in moderate to good yields. Moreover, this study reveals a gentler and environmentally friendly way to access meta-nitration arenes compared to the traditional process.

Back cover (9071-9072).