Organic Letters: Latest Articles (ACS Publications)
Authors: Kai Zhu, Zongqiang Song, Yi Wang, and Fengzhi Zhang
feedproxy.google.com/~r/acs/orlef7/~3/zJRIeyxm7Mc/acs.orglett.0c03614
Organic Letters: Latest Articles (ACS Publications)
Authors: Fu-Qiang Ni, Shu-Qi Wu, Wei Li, Qingjiang Li, and Sheng Yin
feedproxy.google.com/~r/acs/orlef7/~3/hp-mmo9NuAc/acs.orglett.0c03615
Journal of the American Chemical Society: Latest Articles (ACS Publications)
Authors: Arnab Chakraborty, Stefan Ilic, Meng Cai, Bradley J. Gibbons, Xiaozhou Yang, Connor C. Slamowitz, and Amanda J. Morris
feedproxy.google.com/~r/acs/jacsat/~3/A5JW-bNBWTU/jacs.0c09503
Journal of the American Chemical Society: Latest Articles (ACS Publications)
Authors: Paribesh Acharyya, Subhajit Roychowdhury, Manisha Samanta, and Kanishka Biswas
feedproxy.google.com/~r/acs/jacsat/~3/Vld-mHZnpUk/jacs.0c11015
Journal of the American Chemical Society: Latest Articles (ACS Publications)
Authors: Mohammad B. Khaled, Roukaya K. El Mokadem, and Jimmie D. Weaver, III
feedproxy.google.com/~r/acs/jacsat/~3/jGYgkZOanFg/jacs.0c11624
Journal of the American Chemical Society: Latest Articles (ACS Publications)
Authors: Catherine A. J. Hooper⬢, Lucia Cardo⬢, James S. Craig, Lazaros Melidis, Aditya Garai, Ross T. Egan, Viktoriia Sadovnikova, Florian Burkert, Louise Male, Nikolas J. Hodges, Douglas F. Browning, Roselyne Rosas, Fengbo Liu, Fillipe V. Rocha, Mauro A. Lima, Simin Liu, David Bardelang, and Michael J. Hannon
feedproxy.google.com/~r/acs/jacsat/~3/Keh5fSEAuwo/jacs.0c07750
Organic Letters: Latest Articles (ACS Publications)
Authors: Kai Zhu, Zongqiang Song, Yi Wang, and Fengzhi Zhang
feedproxy.google.com/~r/acs/orlef7/~3/zJRIeyxm7Mc/acs.orglett.0c03614
Accounts of Chemical Research: Latest Articles (ACS Publications)
Authors: Zhengxu Cai, Yue Ren, Xiaofang Li, Jianbing Shi, Bin Tong, and Yuping Dong
feedproxy.google.com/~r/acs/achre4/~3/96VQNZRielE/acs.accounts.0c00514
Organic Letters: Latest Articles (ACS Publications)
Authors: Xinmou Wang, Yuming Chen, Hongjian Song, Yuxiu Liu, and Qingmin Wang
feedproxy.google.com/~r/acs/orlef7/~3/9XB3dfzDRLk/acs.orglett.0c03551
Journal of the American Chemical Society: Latest Articles (ACS Publications)
Authors: Hongsun Ryu, Dae Young Park, Kyle M. McCall, Hye Ryung Byun, Yongjun Lee, Tae Jung Kim, Mun Seok Jeong, Jeongyong Kim, Mercouri G. Kanatzidis, and Joon I. Jang
feedproxy.google.com/~r/acs/jacsat/~3/rXrz0SRz9es/jacs.0c09132
![On the Structure of Intermediates in Enyne Gold(I)‐Catalyzed Cyclizations: Formation of trans‐Fused Bicyclo[5.1.0]octanes as a Case Study](https://d-bernier.fr/wp-content/uploads/2020/11/chem202004237-toc-0001-m.png)
Going for gold: The nature of cyclopropyl gold(I) carbene‐type intermediates has been explored as part of a mechanistic study on the gold(I)‐catalyzed formation of trans‐fused bicyclo[5.1.0]octanes. Complete computational analysis, that includes QTAIM theory and NBO analysis, confirms the formation of different species with carbenic or cationic nature as intermediates in the cycloisomerizations of enynes.
The nature of cyclopropyl gold(I) carbene‐type intermediates has been reexamined as part of a mechanistic study on the formation of cis‐ or trans‐fused bicyclo[5.1.0]octanes in a gold(I)‐catalyzed cascade reaction. Benchmark of DFT methods together with QTAIM theory and NBO analysis confirms the formation of distinct intermediates with carbenic or carbocationic structures in the cycloisomerizations of enynes.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Imma Escofet, Helena Armengol‐Relats, Hanna Bruss, Maria Besora, Antonio M. Echavarren
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202004237
I on it! Dialkyl and diphenyl H‐phosphonates undergo dealkylation and dearylation, respectively, upon heating with amines to afford the corresponding ionic salts. The mechanisms for these processes, which form ammonium monosubstituted H‐phosphonate salts held together by H‐bonds, were interrogated both experimentally and theoretically, and the results show that they are very different.
A series of ammonium monosubstituted H‐phosphonate salts were synthesized by combining H‐phosphonate diesters with amines in the absence of solvent at 80 °C. Variation of the ester substituent and amine produced a range of ionic liquids with low melting points. The products and by‐products were analyzed by spectroscopic and spectrometric techniques in order to get a better mechanistic picture of the dealkylation and formal dearylation observed. For dialkyl H‐phosphonate diesters, (RO)2P(O)H (R=alkyl), the reaction proceeds via direct dealkylation with the reactivity increasing in the order R=iPr<Et<Me corresponding to DFT calculated activation enthalpies of 22.6, 20.8, and 17.9 kcal mol−1. For the diphenyl H‐phosphonate diesters, (PhO)2P(O)H, the dearylation was found to proceed via phenol‐assisted formation of a 5‐coordinate intermediate, (PhO)3PH(OH), from which P(OPh)3 and water were eliminated. The presence of an equivalent of water then facilitated the formation of P(OH)2OPh and the amine, R’NH2, subsequently abstracted a proton from it to yield [(PhO)PH(O)O]‐[R’NH3]+.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Keng Lung Lee, Joey Feld, Paul Hume, Tilo Söhnel, Erin Leitao
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202003090
Carbon dioxide promotes cyanohydrins synthesis, enabling facile and iterative homologation reactions for organic synthesis. This traceless, practical and atom‐efficient cyanohydrin synthesis shows a broad substrate scope with high isolated yields of synthetically versatile cyanohydrins. The use of CO2 can be productive in chemical reactions undergoing anionic intermediates and negatively charged transitions states, which can be stabilized by Lewis‐acidic CO2.
Thermodynamic and kinetic control of a chemical process is the key to access desired products and states. Changes are made when a desired product is not accessible; one may manipulate the reaction with additional reagents, catalysts and/or protecting groups. Here we report the use of carbon dioxide to accelerate cyanohydrin synthesis under neutral conditions with an insoluble cyanide source (KCN) without generating toxic HCN. Under inert atmosphere, the reaction is essentially not operative due to the unfavored equilibrium. The utility of CO2‐mediated selective cyanohydrin synthesis was further showcased by broadening Kiliani–Fischer synthesis under neutral conditions. This protocol offers an easy access to a variety of polyols, cyanohydrins, linear alkylnitriles, by simply starting from alkyl‐ and arylaldehydes, KCN and an atmospheric pressure of CO2.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Martin Juhl, Allan R. Petersen, Ji‐Woong Lee
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202003623
Wrapping with ribbons: Chiral bis(urea) amphiphiles can translate their molecular scale chiral information to the mesoscopic level via self‐assembly in water. The morphology of the aggregates can be tuned by varying the enantiomeric excess of the amphiphile, giving access to flat sheets, helical ribbons, and twisted ribbons. The system presents thermo‐responsive aggregation properties, in which a ribbon‐to‐vesicles transition occurs upon heating.
We present the synthesis and self‐assembly of a chiral bis(urea) amphiphile and show that chirality offers a remarkable level of control towards different morphologies. Upon self‐assembly in water, the molecular‐scale chiral information is translated to the mesoscopic level. Both enantiomers of the amphiphile self‐assemble into chiral twisted ribbons with opposite handedness, as supported by Cryo‐TEM and circular dichroism (CD) measurements. The system presents thermo‐responsive aggregation behavior and combined transmittance measurements, temperature‐dependent UV, CD, TEM, and micro‐differential scanning calorimetry (DSC) show that a ribbon‐to‐vesicles transition occurs upon heating. Remarkably, chirality allows easy control of morphology as the self‐assembly into distinct aggregates can be tuned by varying the enantiomeric excess of the amphiphile, giving access to flat sheets, helical ribbons, and twisted ribbons.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Filippo Tosi, José Augusto Berrocal, Marc C. A. Stuart, Sander J. Wezenberg, Ben L. Feringa
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202003403
A complex question: Magnesium complexes of sequential {ONNN}‐type ligands featuring either chiral or meso‐bipyrrolidine cores form as single diastereomers and exhibit exceptionally high activities in rac‐lactide polymerization, fully consuming thousands of monomer equivalents within 5 min, giving poly(lactic acid) of narrow molecular weight distribution and high degree of isotacticity.
The coordination chemistry and the activities in the ring‐opening polymerization catalysis of racemic lactide (LA) of magnesium complexes of a series of {ONNN}‐type sequential monoanionic ligands are described. All ligands include pyridyl and substituted‐phenolate as peripheral groups. The ligands bearing either chiral or meso‐bipyrrolidine cores led to single diastereomeric complexes, whereas the ligands bearing a diaminoethane core led to diastereomer mixtures. All {ONNN}Mg‐X complexes [X=Cl, HMDS (hexamethyldisilazide)] led to highly active and isoselective catalysts. The complexes bearing the chiral bipyrrolidine core exhibited the highest activities (full consumption of 5000 equiv. of rac‐LA at RT within 5 min) and highest isoselectivities (Pm=0.91), as well as a living character. The complexes of the meso‐bipyrrolidine based ligands were almost as active and slightly less stereoselective, while those of the diaminoethane based ligands exhibited reduced activities and isoselectivities.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Tomer Rosen, Jitendrasingh Rajpurohit, Sophia Lipstman, Vincenzo Venditto, Moshe Kol
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202003616
Combining strengths: Carnoquinolines (CarHQs), the first carnosine–8‐hydroxyquinoline hybrids, combine the properties of the natural dipeptide (carnosine) with those of a known copper ionophore (8‐hydroxyquinoline). Conjugation provides multitargeted directed ligands that can target albumin, β‐amyloid (Aβ), copper ions, the copper–Aβ system, and radical and glycating agents. These findings indicate that CarHQs could provide lead compounds for neurodegenerative diseases.
Metal dysregulation, oxidative stress, protein modification, and aggregation are factors strictly interrelated and associated with neurodegenerative pathologies. As such, all of these aspects represent valid targets to counteract neurodegeneration and, therefore, the development of metal‐binding compounds with other properties to combat multifactorial disorders is definitely on the rise. Herein, the synthesis and in‐depth analysis of the first hybrids of carnosine and 8‐hydroxyquinoline, carnoquinolines (CarHQs), which combine the properties of the dipeptide with those of 8‐hydroxyquinoline, are reported. CarHQs and their copper complexes were characterized through several techniques, such as ESI‐MS and NMR, UV/Vis, and circular dichroism spectroscopy. CarHQs can modulate self‐ and copper‐induced amyloid‐β aggregation. These hybrids combine the antioxidant activity of their parent compounds. Therefore, they can simultaneously scavenge free radicals and reactive carbonyl species, thanks to the phenolic group and imidazole ring. These results indicate that CarHQs are promising multifunctional candidates for neurodegenerative disorders and they are worthy of further studies.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Francesco Bellia, Giuseppa Ida Grasso, Ikhlas Mohamed Mohamud Ahmed, Valentina Oliveri, Graziella Vecchio
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202001591
![Catalytic Chemoselective Sulfimidation with an Electrophilic [CoIII(TAML)]−‐Nitrene Radical Complex**](https://d-bernier.fr/wp-content/uploads/2020/11/chem202003566-toc-0001-m.png)
Cobalt‐catalyzed sulfimidation of (aryl)(alkyl)‐substituted sulfides with iminoiodinanes proceeds under mild conditions and with high chemoselectivity in presence of alkenes and weak C−H bonds. PPh4[CoIII(TAMLred)] mediates the nitrene transfer reactions with a high turnover number and frequency, while the electrophilicity of the nitrene radical intermediate determines the chemoselectivity.
The cobalt species PPh4[CoIII(TAMLred)] is a competent and stable catalyst for the sulfimidation of (aryl)(alkyl)‐substituted sulfides with iminoiodinanes, reaching turnover numbers up to 900 and turnover frequencies of 640 min−1 under mild and aerobic conditions. The sulfimidation proceeds in a highly chemoselective manner, even in the presence of alkenes or weak C−H bonds, as supported by inter‐ and intramolecular competition experiments. Functionalization of the sulfide substituent with various electron‐donating and electron‐withdrawing arenes and several alkyl, benzyl and vinyl fragments is tolerated, with up to quantitative product yields. Sulfimidation of phenyl allyl sulfide led to [2,3]‐sigmatropic rearrangement of the initially formed sulfimide species to afford the corresponding N‐allyl‐S‐phenyl‐thiohydroxylamines as attractive products. Mechanistic studies suggest that the actual nitrene transfer to the sulfide proceeds via (previously characterized) electrophilic nitrene radical intermediates that afford the sulfimide products via electronically asynchronous transition states, in which SET from the sulfide to the nitrene radical complex precedes N−S bond formation in a single concerted process.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Nicolaas P. Leest, Jarl Ivar Vlugt, Bas Bruin
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202003566
![C(1)‐Phenethyl Derivatives of [closo‐1‐CB11H12]− and [closo‐1‐CB9H10]− Anions: Difunctional Building Blocks for Molecular Materials](https://d-bernier.fr/wp-content/uploads/2020/11/chem202002997-toc-0001-m.png)
Substitution of [closo‐1‐CB9H10]− and [closo‐1‐CB11H12]− anions with functionalized phenethyl at C(1) and iodine or PhI in the antipodal position gives new building blocks for polar and ionic liquid crystals.
C(1)‐vinylation of [closo‐1‐CB9H10]− (A) and [closo‐1‐CB11H12]− (B) with 4‐benzyloxystyryl iodide followed by hydrogenation of the double bond and reductive deprotection of the phenol functionality led to C(1)‐(4‐hydroxyphenethyl) derivatives. The phenol functionality was protected as the acetate. The esters were then treated with PhI(OAc)2 and the resulting isomers were separated kinetically (for derivatives of anion A) or by chromatography (for derivatives of anion B) giving the difunctionalized building blocks in overall yields of 9 % and 50 %, respectively. A similar series of reactions was performed starting with anions A and B and 4‐methoxystyryl bromide and iodide. Significant differences in the reactivity of derivatives of the two carborane anions were rationalized with DFT computational results. Application of the difunctionalized carboranes as building blocks was demonstrated through preparation of two ionic liquid crystals. The extensive synthetic work is accompanied by single crystal XRD analysis of six derivatives.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Rafał Jakubowski, Anna Pietrzak, Andrienne C. Friedli, Piotr Kaszyński
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202002997
Relax and pores: Extra‐large‐pore aluminosilicate zeolite Al‐NUD‐6 with a 16‐membered‐ring pore channel was synthesized. Removal of the organic templates in Al‐NUD‐6 resulted in a distorted pore structure due to structure relaxation. The incorporation of aluminium resulted in both medium and strong acid sites in Al‐NUD‐6H, implying its potential use as an acidic catalyst.
Pure silica zeolites possessing uniform micropores, large surface area and high thermal and chemical stability have been widely studied and used in the fields of fine chemicals and oil industry. The incorporation of aluminium into the framework of silica zeolites changes their properties, making them more industrially useful as adsorbents and catalysts. Herein, we report the synthesis and characterization of an extra‐large‐pore aluminosilicate zeolite NUD‐6 with a 16‐membered‐ring pore channel. Aluminium was directly incorporated into the zeolite NUD‐6 framework, as confirmed by 27Al MAS NMR studies and ammonia temperature‐programmed desorption probes. Al‐NUD‐6 was not stable when heated at 550 °C to remove the organic templates. However, the organic templates in Al‐NUD‐6 could be removed by oxidation in nitric acid at room temperature. The obtained Al‐NUD‐6H retained the crystalline structure and possessed both micropores and mesopores despite the occurrence of severe structural distortions due to the presence of the corner‐sharing Q3 Si2O7 units. The incorporation of aluminium resulted in both medium and strong acid sites in Al‐NUD‐6H, and could facilitate its use in adsorption and catalysis.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Wenwen Zi, Xianshu Cai, Feng Jiao, Hongbin Du
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202003183
A three‐arm‐shaped molecule possessing pyridine‐acetylene‐phenol units was developed as a new kind of host having preorganized three‐dimensional hydrogen‐bonding sites. The preparation of this host was relatively easy compared to a cage‐shaped analogue because no macrocyclization step was required. This host associated with lipophilic glycosides, and the affinities were sufficiently high to be comparable to those of the cage‐shaped analogue.
Generally, cage‐shaped hosts for saccharides can bind strongly to guest molecules because of the three‐dimensional preorganized hydrogen‐bonding sites. However, the preparation of cage molecules is often difficult because of the low yield of the macrocyclization step. Here, we report a three‐arm‐shaped molecule possessing pyridine‐acetylene‐phenol units as a new kind of host having a preorganized three‐dimensional hydrogen‐bonding site. This three‐arm‐shaped host was readily prepared compared to a cage‐shaped analogue. This host associated with lipophilic glycosides to form chiral complexes, and the association constants were sufficiently high as to be comparable to those of the cage‐shaped analogue. Furthermore, this host extracted native monosaccharides into a lipophilic solvent.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Yuki Ohishi, Kentaro Masuda, Kazuki Kudo, Hajime Abe, Masahiko Inouye
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202004147
![A Giant [8+12] Boronic Ester Cage with 48 Terminal Alkene Units in the Periphery for Postsynthetic Alkene Metathesis](https://d-bernier.fr/wp-content/uploads/2020/11/chem202003675-toc-0001-m.png)
Covalent cage in cage by a metathesis approach. Exploiting boronic ester condensation, a shape‐persistent organic cage that contains terminal alkene units was used as covalent template to generate a second sphere hydrocarbon exoskeleton.
Dynamic covalent chemistry (DCC) is a powerful synthetic tool to construct large defined molecules in one step from rather simple precursors. The advantage of the intrinsic dynamics of the applied reversible reaction steps is a self‐correction under the chosen conditions, to achieve high yields of the target compound. To date, only a few examples are known, in which DCC was used to build up a molecular defined but larger product that was chemically transferred to a more stable congener in a second (irreversible) step. Here, we present a nanometer‐sized [8+12] boronic ester cage containing 48 peripheral terminal alkene units which allows to put a hydrocarbon exoskeleton around the cage via alkene metathesis.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Martin Hähsler, Michael Mastalerz
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202003675
The increasing demand for high‐performance rechargeable energy storage systems has stimulated the exploration of advanced electrode materials, such as MXenes, 2D inorganic transition metal carbides/nitrides. Recently, interlayer space engineering of MXenes by different chemical strategies have been widely investigated in the design of functional materials for various applications. In this review, an overview of the most recent progress of 2D MXenes engineering by intercalation, surface modification as well as heterostructures design is provided.
The increasing demand for high‐performance rechargeable energy storage systems has stimulated the exploration of advanced electrode materials. MXenes are a class of two‐dimensional (2D) inorganic transition metal carbides/nitrides, which are promising candidates in electrodes. The layered structure facilitates ion insertion/extraction, which offers promising electrochemical characteristics for electrochemical energy storage. However, the low capacity accompanied by sluggish electrochemical kinetics of electrodes as well as interlayer restacking and collapse significantly impede their practical applications. Recently, interlayer space engineering of MXenes by different chemical strategies have been widely investigated in designing functional materials for various applications. In this review, an overview of the most recent progress of 2D MXenes engineering by intercalation, surface modification as well as heterostructures design is provided. Moreover, some critical challenges in future research on MXene‐based electrodes have been also proposed.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Jiayong Tang, Xia Huang, Tengfei Qiu, Xiyue Peng, Tingting Wu, Lei Wang, Bin Luo, Lianzhou Wang
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202002283
An analogy between embroidered patterns on cloths and self‐assembled monolayers formed on surfaces is depicted in the cover image (designed by Dr. Kaja Sitkowska). While embroidery makes it possible to modify and enrich a previously formed pattern through sequential operations, achieving such a level of control is generally difficult in surface‐based self‐assembly processes. This work reports on how to adsorb alkoxy‐pyrene derivatives (green beads) at highly oriented pyrolytic graphite (purple cover) onto a previously formed naphthalenediimide monolayer (copper branches). More information can be found in the Communication by E. W. Meijer, B. L. Feringa, et al. (DOI: 10.1002/chem.202004008).
Wiley: Chemistry – A European Journal: Table of Contents
Authors: G. Henrieke Heideman, José Augusto Berrocal, Meike Stöhr, E. W. Meijer, Ben L. Feringa
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202004910
Close to the bone: Metal–organic frameworks, coordination polymers and discrete coordination complexes can be used in the treatment of bone disorders. This Review provides an insight into recent progress in this area.
Osteoporosis, Paget’s disease and osteosarcoma are a few examples of bone tissue disorders that affect millions of people worldwide. These conditions can strictly limit the lifestyle of patients and may even lead to their demise. To prevent this or, at least, try to manage the situation, there are several treatments available on the market. Notwithstanding, research has been driven by the possibility to improve the existing therapies, as well as to find new approaches that could better respond to these diseases. In this Review the path is shown through which, in recent years, coordination compounds have been prepared and manufactured to be applied in the management of bone tissue disorders. Starting with the design and preparation of the coordination compounds with various dimensionalities, two approaches have been used: (1) they are prepared as three‐dimensional cages that can act as delivery systems for therapeutic substances, or (2) they are constructed/prepared from compounds with intrinsic therapeutic properties. Following this, several strategies have been explored to manufacture the effective delivery to the patients. The versatility of coordination compounds has allowed their use in the preparation of drug tablets, coatings for titanium implants, or even scaffolds for bone tissue engineering. In the end, it becomes clear that these compounds can be a valuable approach to reach a better treatment for bone tissue disorders. Nonetheless, along the road, a few bumps have appeared concerning the therapeutic profile, such as the effect of the structural arrangement or particle size.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Jéssica S. Barbosa, Ricardo F. Mendes, Flávio Figueira, Vítor M. Gaspar, João F. Mano, Susana S. Braga, João Rocha, Filipe A. Almeida Paz
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202004529
A biomarker: (18R)‐Aldosterone‐18‐β‐d‐glucuronide (1) is an important biological marker. A new synthesis is described starting from aldosterone 21‐acetate and the trichloroacetimidate of 2,3,4‐triacetylglucuronic acid methyl ester in the presence of TMSOTf, which is followed by two enzymatic steps. In this process also the novel C‐20‐glucuronides (2) are obtained. The so far unknown stereochemistry at C‐18 in (1) was determined by NOESY experiments.
Aldosterone 1 is a mineralocorticoid, it has great influence on the blood pressure and its glucuronide is an important marker for the detection of several diseases. Here, we describe the chemical synthesis of different aldosterone‐18‐ and 20‐glucuronides. Reaction of trimethylsilyl 2,3,4‐tri‐ acetyl‐1‐β‐glucuronic acid methyl ester 5 b and aldosterone diacetate 11 in the presence of TMSOTf gave the 18‐α‐glucuronide 9 a. The 18‐β‐glucuronide 15 b and the 20‐β‐glucuronide 16 b could be obtained by reaction of methyl 2,3,4‐tri‐O‐isobutyryl‐1α‐glucuronate trichloroacetimidate 14 and aldosterone 21‐acetate 8 in the presence of TMSOTf or BF3⋅OEt2. Finally, reaction of aldosterone 21‐acetate 8 and methyl 2,3,4‐triacetyl‐1α‐glucuronate trichloroacetimidate 19 in the presence of TMSOTf gave the corresponding methyl 18‐β‐triacetylglucuronate 9 b, which was transformed into the desired aldosterone‐18‐β‐glucuronide 3 by two enzyma‐ tic transformations.
Wiley: Chemistry – A European Journal: Table of Contents
Authors: Somraj Guha, Soundararasu Senthilkumar, Edgar Voß, Lutz F. Tietze
chemistry-europe.onlinelibrary.wiley.com/doi/abs/10.1002/chem.202004154
