Dihydroxylation Studies of Isoquinolinones: Synthesis of the EF-Ring of Lysolipin I

Synthesis ◽  
2021 ◽  
Author(s):  
Maximilian J. B. Heinemann ◽  
Thomas Voigt ◽  
Dirk Menche

Inspired by the potent polycyclic xanthone antibiotic Lysolipin I, a general study on asymmetric dihydroxylation reactions of variously substituted isoquinolinones was performed. Different isoquinolinones were efficiently prepared, either by a Pomeranz-Fritsch type condensation or a Curtius rearrangement. Under a broad variety of conventional oxygenation procedures they proved very unreactive. However, either by suitable substitution of the appending aromatic ring or more forcing conditions a dihydroxylation could finally be performed, which allowed for synthesis of the EF-ring of Lysolipin I.

Author(s):  
Ade Arsianti ◽  
Chie Aoki Utsubo ◽  
Fadilah Fadilah ◽  
Anton Bahtiar ◽  
Dadan Ramadhan Apriyanto ◽  
...  

Objective: In this work, we aim to synthesize gallic acid derivatives with chiral center and to evaluate its anti-hepatitis C virus (anti-HCV) activity.Methods: Synthesis of the target derivatives was started from esterification of commercially available boc deprotection (Boc)-L-threonine with allyl bromide, followed by Boc with HCl/EtOAc, amidation, and Sharpless asymmetric dihydroxylation with (DHQ)2PHAL or (DHQD)2PHAL as a ligand to give desired gallic acid derivatives. The synthesized gallic acid derivatives were then evaluated for anti-HCV activity and cytotoxicity.Results: The target derivatives were successfully synthesized in ranging from 20% to 30% of yield. Anti-HCV activity of the derivatives is greatly improved by the presence of chiral center, hydroxyl group, and monomethoxy group on the aromatic ring, with showed no cytotoxicity. This fact revealed that the chiral center, hydroxyl group, and monomethoxy group on the aromatic ring of gallic acid derivatives are responsible for its anti-HCV activity. Moreover, gallic acid derivative which possesses a chiral center of bottom facial stereochemistry was found to have a stronger anti-HCV activity than gallic acid derivative with chiral center of top facial stereochemistry. Suggesting that, bottom facial stereocenter in gallic acid derivative was more effective for anti-HCV activity than the top facial stereocenter.Conclusion: Gallic acid derivatives with chiral center exhibited a greater antiviral activity against HCV than gallic acid. Thus, the derivatives should be considered as a promising candidate for the treatment of HCV infection. 


2020 ◽  
Author(s):  
Hui Zhao ◽  
Kai Gao ◽  
Haichen Ma ◽  
Tsz Chun Yip ◽  
Wei-Min Dai

The C19–C30 bis-THF fragment of the proposed structure of iriomoteolide-13a has been synthesized. The w-mesyloxy-substituted stereotetrad possessing three continuous hydroxy groups was generated by <i>anti</i>-aldol reaction and asymmetric dihydroxylation (AD). Upon heating in pyridine the stereotetrad underwent an S<sub>N</sub>2 cyclization to form the C19–C22 THF ring. It was followed by an intramolecular <i>syn</i>-oxypalladation of the C28 chiral allylic alcohol to give the C23–C26 THF ring.


2019 ◽  
Author(s):  
Benjamin Lipp ◽  
Lisa Marie Kammer ◽  
Murat Kucukdisli ◽  
Adriana Luque ◽  
Jonas Kühlborn ◽  
...  

Simultaneous sulfonylation/arylation of styrene derivatives is achieved in a photoredox-catalyzed three-component reaction using visible light. A broad variety of difunctionalized products is accessible in mostly excellent yields and high diastereoselectivity. The developed reaction is scalable and suitable for the modification of styrene-functionalized biomolecules. Mechanistic investigations suggest the transformation to be operating through a designed sequence of radical formation and radical combination.<br>


2018 ◽  
Vol 28 (1) ◽  
pp. 201-207
Author(s):  
Kamen Kirilov

Globalization, commodity parity, consumer sovereignty, super competition and a broad variety of other factors, including the roll-out of the mass media, the emergence and rapid rise of the new media formats and platforms as well as the exchange of information provided by social networks pose new challenges for the advertising industry. Throughout its 150 years of history, since we have known it as a distinct occupation and practice, advertising shows adaptive sustainability quality and greatly enhance its capacity as features, forms, user approaches and distribution channels. Nevertheless, by its very nature, advertising retains the constant of an asymmetric pattern of communication in which, in nowadays environment, the success of effort is expressed in the formula of understanding others and the willingness they to understand us in return. In practice, beyond the abstract of this formula, the effort of advertisers in the process of creating and planning a certain campaign would be greatly facilitated by putting the basic principles of empathy theory. Numerous experiments and studies of this human ability establish working models to achieve effective contact both at the level of personal communication and in the cases of direct and indirect communication with huge quantity and variety of audiences with specific composition. Synthesized and brought to a universal level of application, the basic principle of empathy is the ability, rather cognitive than emotional, to understand and to feel the feelings of others. The achievements in this psychology field currently apply mainly to psychotherapy, clinical psychiatry, pedagogy and political rhetoric theories and ractices. Experience proves that empathic skills help the communicator for faster, easier, more effective and more properly understood and accordingly more efficient as a moderator. This article provokes a new paradigm for advertisers in communicating with the public - about the content, forms and planning of communication activities of the principles of empathy. The goal of the effort is clear - creating more effective communication and achieving a sustainablecompetitive advantage.


2020 ◽  
Vol 07 ◽  
Author(s):  
Christian Trapp ◽  
Corinna Schuster ◽  
Chris Drewniok ◽  
Dieter Greif ◽  
Martin Hofrichter

Background:: Chiral β-hydroxy esters and α-substituted β-hydroxy esters represent versatile building blocks for pheromones, β-lactam antibiotics and 1,2- or 1,3-aminoalcohols. Objective:: Synthesis of versatile α-substituted β-keto esters and their diastereoselective reduction to the corresponding syn- or anti-α-substituted β-hydroxy esters. Assignment of the relative configuration by NMR-spectroscopy after a CURTIUS rearrangement of α-substituted β-keto esters to 4-substituted 5-methyloxazolidin-2-ones. Method:: Diastereoselective reduction was achieved by using different LEWIS acids (zinc, titanium and cerium) in combination with complex borohydrides as reducing agents. Assignment of the relative configuration was verified by 1H-NMR spectroscopy after CURTIUS-rearrangement of α-substituted β-hydroxy esters to 4-substituted 5-methyloxazolidin-2-ones. Results:: For the syn-selective reduction, titanium tetrachloride (TiCl4) in combination with a pyridine-borane complex (py BH3) led to diastereoselectivities up to 99% dr. High anti-selective reduction was achieved by using cerium trichloride (CeCl3) and steric hindered reducing agents such as lithium triethylborohydride (LiEt3BH). After CURTIUS-rearrangement of each α-substituted β-hydroxy ester to the corresponding 4-substituted 5-methyloxazolidin-2-one, the relative configuration was confirmed by 1H NMR-spectroscopy. Conclusion:: We have expanded the procedure of LEWIS acid-mediated diastereoselective reduction to bulky α-substituents such as the isopropyl group and the electron withdrawing phenyl ring.


1987 ◽  
Vol 52 (7) ◽  
pp. 1780-1785 ◽  
Author(s):  
Petr Kuzmič ◽  
Libuše Pavlíčková ◽  
Milan Souček

Ultraviolet irradiation of the title compound I in the presence of butylamine gave predominantly products of nucleophilic photosubstitution by the amine, i.e., nitroanilines IIa and IIb. Besides, small amounts of products of hydrolysis (phenol III) and reductive coupling (azoxybenzene IV) were also formed. Comparison of the overall photolysis rate of I with that of 3,4-dimethoxy-1-nitrobenzene (V) indicates a minor loss of reactivity, most probably due to some deviation from coplanarity of the activating nitro group and the aromatic ring.


Author(s):  
Dean Jacobsen ◽  
Olivier Dangles

Chapter 2 presents the amazing variety of running waters, lakes, ponds, and wetlands found at high altitudes. These waterbodies are not equally distributed among the world’s high altitude places, but tend to be concentrated in certain areas, primarily determined by regional climate and topography. Thus, a large proportion of the world’s truly high altitude aquatic systems are found at lower latitudes, mostly in the tropics. The chapter presents general patterns in the geographical distribution of high altitude waters, and gives examples of some of the most extreme systems. High altitude aquatic systems and habitats cover a broad variety in dynamics and physical appearance. These differences may be related to, for example, water source (glacier-fed, rain-fed, or groundwater-fed streams), geological origin (e.g. glacial, volcanic, or tectonic lakes), or catchment slope and altitude (different types of peatland wetlands). This is exemplified and richly illustrated through numerous photos.


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