33878-99-8Relevant academic research and scientific papers
Synthesis of the Tetracyclic Structure of Batrachotoxin Enabled by Bridgehead Radical Coupling and Pd/Ni-Promoted Ullmann Reaction
Sakata, Komei,Wang, Yinghua,Urabe, Daisuke,Inoue, Masayuki
, p. 130 - 133 (2018)
The steroidal ABCD-ring system of the potent neurotoxin batrachotoxin was efficiently assembled in a convergent fashion. Bridgehead radical coupling between the simple AB-ring and D-ring fragments (3 and 4) formed the sterically congested linkage at the C9-oxygen-attached tetrasubstituted carbon. The C-ring was then cyclized by the Pd/Ni-promoted Ullmann reaction of the vinyl triflate and vinyl bromide of 19, giving rise to tetracyclic structure 1.
Proline mediated asymmetric ketol cyclization: A template reaction
Rajagopal,Moni,Subramanian,Swaminathan
, p. 1631 - 1634 (1999)
1H, 13C and ATR-FTIR Spectroscopic studies reveal that the asymmetric cyclization of prochiral triones 1 and 2 in the presence of S-proline is a template reaction.
Identification of Inhibitors of Cholesterol Transport Proteins Through the Synthesis of a Diverse, Sterol-Inspired Compound Collection
Laraia, Luca,Olsen, Asger Hegelund,Whitmarsh-Everiss, Thomas
supporting information, p. 26755 - 26761 (2021/11/17)
Cholesterol transport proteins regulate a vast array of cellular processes including lipid metabolism, vesicular and non-vesicular trafficking, organelle contact sites, and autophagy. Despite their undoubted importance, the identification of selective modulators of this class of proteins has been challenging due to the structural similarities in the cholesterol-binding site. Herein we report a general strategy for the identification of selective inhibitors of cholesterol transport proteins via the synthesis of a diverse sterol-inspired compound collection. Fusion of a primary sterol fragment to an array of secondary privileged scaffolds led to the identification of potent and selective inhibitors of the cholesterol transport protein Aster-C, which displayed a surprising preference for the unnatural-sterol AB-ring stereochemistry and new inhibitors of Aster-A. We propose that this strategy can and should be applied to any therapeutically relevant sterol-binding protein.
Biocatalytic Approaches to the Enantiomers of Wieland–Miescher Ketone and its Derivatives
Bertuletti, Susanna,Bayout, Ikram,Bassanini, Ivan,Ferrandi, Erica E.,Bouzemi, Nassima,Monti, Daniela,Riva, Sergio
, p. 3992 - 3998 (2021/04/09)
Biocatalytic approaches have been investigated in order to isolate the enantiomers of Wieland–Miescher ketone (1) and of its alcoholic derivatives (cis-2 and trans-3). Specifically, two enzymes from our in-house metagenomic collection of oxidoreductases, IS2-SDR and Dm7α-HSDH, catalyzed the kinetic resolution of the starting racemic ketone 1 or its complete conversion into two diastereomeric products, respectively. Moreover, the kinetic resolution of the racemic cis-alcohol (2) was very efficiently obtained (E?2.000) by lipase PS catalyzed acetylation in dry acetone. All the products were isolated with ee≥95 %. Simple chemical elaborations of some of them allowed to isolate the missing enantiomers.
Potent Anti-Inflammatory, Arylpyrazole-Based Glucocorticoid Receptor Agonists That Do Not Impair Insulin Secretion
Burke, Susan J.,Campagna, Shawn R.,Collier, J. Jason,Dunlap, Lee E.,Fisch, Alexander R.,Kennedy, Brandon J.,Kirkland, Justin K.,Lato, Ashley M.,Prevatte, Carson W.,Smith, Russell T.,Vogiatzis, Konstantinos D.
, p. 1568 - 1577 (2021/10/04)
Glucocorticoids (GCs) are widely used in medicine for their role in the treatment of autoimmune-mediated conditions, certain cancers, and organ transplantation. The transcriptional activities GCs elicit include transrepression, postulated to be responsible for the anti-inflammatory activity, and transactivation, proposed to underlie the undesirable side effects associated with long-term use. A GC analogue that could elicit only transrepression and beneficial transactivation properties would be of great medicinal value and is highly sought after. In this study, a series of 1-(4-substituted phenyl)pyrazole-based GC analogues were synthesized, biologically screened, and evaluated for SARs leading to the desired activity. Activity observed in compounds bearing an electron deficient arylpyrazole moiety showed promise toward a dissociated steroid, displaying transrepression while having limited transactivation activity. In addition, compounds 11aa and 11ab were found to have anti-inflammatory efficacy comparable to that of dexamethasone at 10 nM, with minimal transactivation activity and no reduction of insulin secretion in cultured rat 832/13 beta cells.
Assessing the Recyclability of Supramolecularly Assembled Organocatalytic Species: A Theoretical Insight
Llorens, Lluis,Llanes, Patricia,Fianchini, Mauro,Pericàs, Miquel A.
, p. 475 - 484 (2020/03/19)
Asymmetric organocatalytic synthesis is a powerful tool in organic chemistry to achieve desired stereoisomers in high purity via mild catalytic routes. The immobilization of homogeneous catalytic species onto heterogeneous phases embodies the evolution of asymmetric catalysis, since it allows the recycling of the catalyst for several runs until degradation. Previously reported non-covalent immobilization of proline-based catalysts for aldol reaction onto magnetic nanoparticles functionalized with β-cyclodextrin (MNP-β-CB) demonstrated the viability of the methodology. This paper proposes two new catalyst recycling strategies based on Cucurbit[7]uril (CB[7]) for the aldol reaction and the Robinson annulation. These recycling methodologies are conceptually different. The former relies on the homogeneous encapsulation of the catalyst in cucurbituril, CB[7] ? Cat, and its recycling in the aqueous phase by extraction of the aldol product with organic solvents. The latter relies on the heterogeneous encapsulation of the catalyst as MNP-CB[7] ? Cat2 system and its recycling by magnetic harvesting. Density functional theory (DFT) calculations have been employed to rationalize the thermodynamics of experimental results, and to suggest caveats and plausible improvements in view of a future catalytic design.
Preparation method of (S)-(+)-3,4,8,8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone
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Paragraph 0021-0026, (2019/03/08)
The invention relates to a preparation method of (S)-(+)-3,4,8,8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone. According to the preparation method, an L-proline derivative is used as a chiral catalyst and microwave radiation is introduced into chiral preparation of the (S)-(+)-3,4,8,8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone for the first time through asymmetric Robinson cyclization reaction under conventional conditions or microwave irradiation conditions. Under proper power, an L-prolinamide type catalyst can keep excellent catalysis performance and the catalysis reaction time isshortened; compared with room-temperature stirring conditions, the synthesis efficiency is greatly improved. The molecular collision is aggravated through the microwave radiation and an intermediatecan more easily pass through an energy barrier to form a transition state, so that the reaction time is remarkably shortened, the preparation efficiency of the (S)-(+)-3,4,8,8a-tetrahydro-8a-methyl-1,6-(2H,7H)-naphthoquinone is greatly improved and the synthesis period is shortened. The method is low in cost, simple and rapid, high in yield and good in stereoselectivity.
Chemoselective Oxidation of Equatorial Alcohols with N-Ligated λ3-Iodanes
Mikhael, Myriam,Adler, Sophia A.,Wengryniuk, Sarah E.
supporting information, p. 5889 - 5893 (2019/08/26)
The site-selective and chemoselective functionalization of alcohols in complex polyols remains a formidable synthetic challenge. Whereas significant advancements have been made in selective derivatization at the oxygen center, chemoselective oxidation to the corresponding carbonyls is less developed. In cyclic systems, whereas the selective oxidation of axial alcohols is well known, a complementary equatorial selective process has not yet been reported. Herein we report the utility of nitrogen-ligated (bis)cationic λ3-iodanes (N-HVIs) for alcohol oxidation and their unprecedented levels of selectivity for the oxidation of equatorial over axial alcohols. The conditions are mild, and the simple pyridine-ligated reagent (Py-HVI) is readily synthesized from commercial PhI(OAc)2 and can be either isolated or generated in situ. Conformational selectivity is demonstrated in both flexible 1,2-substituted cyclohexanols and rigid polyol scaffolds, providing chemists with a novel tool for chemoselective oxidation.
Hydrodealkenylative C(sp3)–C(sp2) bond fragmentation
Smaligo, Andrew J.,Swain, Manisha,Quintana, Jason C.,Tan, Mikayla F.,Kim, Danielle A.,Kwon, Ohyun
, p. 681 - 685 (2019/06/11)
Chemical synthesis typically relies on reactions that generate complexity through elaboration of simple starting materials. Less common are deconstructive strategies toward complexity—particularly those involving carbon-carbon bond scission. Here, we introduce one such transformation: the hydrodealkenylative cleavage of C(sp3)–C(sp2) bonds, conducted below room temperature, using ozone, an iron salt, and a hydrogen atom donor. These reactions are performed in nonanhydrous solvents and open to the air; reach completion within 30 minutes; and deliver their products in high yields, even on decagram scales. We have used this broadly functionality tolerant transformation to produce desirable synthetic intermediates, many of which are optically active, from abundantly available terpenes and terpenoid-derived precursors. We have also applied it in the formal total syntheses of complex molecules.
A synthetic approach to (±)-aristomakine
Perni, Robert B.,Gribble, Gordon W.
, p. 75 - 84 (2018/07/03)
We describe the synthesis of trans-11b-methyl-2,3,4,6,11,11b-hexahydro-1H-benzo[a]carbazol-3-ol (2) in five steps from the Wieland-Miescher ketone 3 in 17% overall yield. The N-benzyl analogue (trans-11-Benzyl-11b-methyl-2,3,4,6,11,11b-hexahydro-1H-benzo[a]carbazol-3-ol) 15 was likewise prepared. Attempts thus far to fashion (±)-aristomakine (1) from 2, 15, or derivatives have not been successful.
