68882-71-3Relevant academic research and scientific papers
Jatrophone Analogues: Synthesis of cis- and trans-Normethyljatropholactones
Smith, Amos B.,Malamas, Michael S.
, p. 3442 - 3447 (1982)
This, a full account, discloses an efficient, convergent synthesis of two novel analogues of the macrocyclic antitumor diterpene jatrophone (1).We term these analogues cis- and trans-normethyljatropholactone (2 and 3, respectively).Our approach in each case begins with the bis(trimethylsilyloxy) ketone 7 and the requisite acetylenic or trans ester-aldehyde, 8 or 12a.Application of our previously developed 3(2H)-furanone synthetic protocol consisting of aldol condensation of the lithium enolate derived from 7 with the respective ester-aldehydes 8 or 12a, followed byoxidation (Collins reagent) and acid-catalyzed cyclization-dehydration, affords spirofuranone 6c and 14c, respectively, in 52percent and 45percent overall yields.Sodium borohydride reduction, ester hydrolysis, and closure of the macrolide by employing the conditions of Mukaiyama (i.e., 1-methyl-2-chloropyridinium iodide-/Et3N/CH3CN) in the case of spirofuranone 14a leads directly to trans-normethyljatropholactone (3), while completion of cis-normethyljatropholactone (2) requires first semihydrogenation; the latter was accomplished by employing PdSO4 in pyridine as the catalyst.The overall yields of 2 and 3, based on 7, were 23percent and 21percent, respectively.
A New Formal Synthetic Route to Entecavir
Liu, Lixia,Sun, Yongli,Wang, Jiwu,Ou, Wentao,Wang, Xiaoji,Huang, Shuangping
, p. 748 - 752 (2019)
We describe a new and straightforward approach to the formal synthesis of the hepatitis B virus inhibitor entecavir, an important hepatitis B drug, in ten steps overall. Key features of the route are a Morita-Baylis-Hillman reaction, a Sharpless asymmetric epoxidation, a reductive epoxide opening of an α,β-epoxy ketone, and a Riley selenium dioxide oxidation.
Late-Stage Intermolecular Allylic C-H Amination
Clark, Joseph R.,Dixon, Charlie F.,Feng, Kaibo,Han, Wei,Ide, Takafumi,Koch, Vanessa,Teng, Dawei,Wendell, Chloe I.,White, M. Christina
supporting information, p. 14969 - 14975 (2021/10/01)
Allylic amination enables late-stage functionalization of natural products where allylic C-H bonds are abundant and introduction of nitrogen may alter biological profiles. Despite advances, intermolecular allylic amination remains a challenging problem due to reactivity and selectivity issues that often mandate excess substrate, furnish product mixtures, and render important classes of olefins (for example, functionalized cyclic) not viable substrates. Here we report that a sustainable manganese perchlorophthalocyanine catalyst, [MnIII(ClPc)], achieves selective, preparative intermolecular allylic C-H amination of 32 cyclic and linear compounds, including ones housing basic amines and competing sites for allylic, ethereal, and benzylic amination. Mechanistic studies support that the high selectivity of [MnIII(ClPc)] may be attributed to its electrophilic, bulky nature and stepwise amination mechanism. Late-stage amination is demonstrated on five distinct classes of natural products, generally with >20:1 site-, regio-, and diastereoselectivity.
CYCLOPENTYL NUCLEOSIDE ANALOGS AS ANTI-VIRALS
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Paragraph 0271, (2020/07/07)
Described herein are cyclopentyl nucleoside analogs, pharmaceutical compositions that include one or more cyclopentyl nucleoside analogs and methods of using the same to treat HBV, HDV and/or HIV.
Novel synthesis method of hepatitis B treating medicine entecavir
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Paragraph 0019; 0035-0037, (2019/01/08)
The invention discloses a novel method for synthesizing entecavir. The novel method takes a compound with a known formula 9 as a starting raw material, and a target molecule is synthesized through a series of reactions including a Morita-Baylis-Hillman reaction, a Sharpless asymmetric epoxidation reaction, TBSCl hydroxyl protection, an opening epoxidation reaction, TBSCl hydroxyl protection, a step of reducing carbonyl into double bonds, SeO2 one-step oxidization double-bond alpha-site H ketone formation reaction, a step of reducing ketone into hydroxyl through lithium triethylborohydride andthe like. The design of a whole route is unique and novel; a reaction process has mild reaction conditions and a rapid speed; side reactions are relatively few and the operation is simple and convenient; conventional chemical reagents are utilized in the route; the raw material is cheap and easy to obtain and the synthesis cost can be greatly reduced.
Chemo-Enzymatic Oxidative Rearrangement of Tertiary Allylic Alcohols: Synthetic Application and Integration into a Cascade Process
Brenna, Elisabetta,Crotti, Michele,De Pieri, Matteo,Gatti, Francesco G.,Manenti, Gabriele,Monti, Daniela
supporting information, p. 3677 - 3686 (2018/06/04)
A chemo-enzymatic catalytic system, comprised of Bobbitt's salt and laccase from Trametes versicolor, allowed the [1,3]-oxidative rearrangement of endocyclic allylic tertiary alcohols into the corresponding enones under an Oxygen atmosphere in aqueous media. The yields were in most cases quantitative, especially for the cyclopent-2-en-1-ol or the cyclohex-2-en-1-ol substrates without an electron withdrawing group (EWG) on the side chain. Transpositions of macrocyclic alkenols or tertiary alcohols bearing an EWG on the side chain were instead carried out in acetonitrile by using an immobilized laccase preparation. Dehydro-Jasmone, dehydro-Hedione, dehydro-Muscone and other fragrance precursors were directly prepared with this procedure, while a synthetic route was developed to easily transform a cyclopentenone derivative into trans-Magnolione and dehydro-Magnolione. The rearrangement of exocyclic allylic alcohols was tested as well, and a dynamic kinetic resolution was observed: α,β-unsaturated ketones with (E)-configuration and a high diastereomeric excess were synthesized. Finally, the 2,2,6,6-tetramethyl-1-piperidinium tetrafluoroborate (TEMPO+BF4?)/laccase catalysed oxidative rearrangement was combined with the ene-reductase/alcohol dehydrogenase cascade process in a one-pot three-step synthesis of cis or trans 3-methylcyclohexan-1-ol, in both cases with a high optical purity. (Figure presented.).
Highly Reactive and Tracelessly Cleavable Cysteine-Specific Modification of Proteins via 4-Substituted Cyclopentenone
Yu, Jian,Yang, Xiaoyue,Sun, Yang,Yin, Zheng
supporting information, p. 11598 - 11602 (2018/09/10)
A rapid and cysteine-specific modification of proteins using 4-substituted cyclopentenone via a Michael addition tandem elimination reaction was developed. Compared to the classical method, this reaction featured fast kinetics with a stable product. More importantly, this conjugation could be tracelessly removed by exchange with a Michael addition donor. The conjugation and regeneration process not only exhibited little change to the structures or conformations of the proteins but also exhibited little disturbance to their biological functions, such as their enzymatic activities.
Catalytic Enantioselective [10+4] Cycloadditions
Donslund, Bjarke S.,Jessen, Nicolaj Inunnguaq,Bertuzzi, Giulio,Giardinetti, Maxime,Palazzo, Teresa A.,Christensen, Mette Louise,J?rgensen, Karl Anker
supporting information, p. 13182 - 13186 (2018/09/12)
The first peri- and stereoselective [10+4] cycloaddition between catalytically generated amino isobenzofulvenes and electron-deficient dienes is described. The highly stereoselective catalytic [10+4] cycloaddition exhibits a broad scope with high yields,
Cascade Radical Cyclization to Vinylogous Carbonates/Carbamates for the Synthesis of Oxa- and Aza-Angular Triquinanes: Diastereoselectivity Depends on the Ring Size of Radical Precursor
Gharpure, Santosh J.,Niranjana,Porwal, Suheel K.
, p. 2954 - 2967 (2018/07/21)
An efficient strategy was developed for the stereoselective construction of oxa- and aza-angular triquinanes employing a cascade 5 - exo - trig radical cyclization to vinylogous carbonates and carbamates. The radical precursors are readily prepared from 2-(hydroxymethyl)cyclopentenone/cyclohexenones. High diastereoselectivity is observed for the formation of angular oxa- and azatriquinanes. Diastereoselectivity drops when six-membered radical precursors are used. The strategy is found to be useful to incorporate synthetically challenging moieties such as spiroindoline, lactone-bearing, and uracil-fused angular triquinanes in a concise manner.
Transition-metal-free nucleophilic allylic substitutions of Morita–Baylis–Hillman bromides with aliphatic and aromatic amines
Baioui, Narjes,Elleuch, Haitham,Rezgui, Farhat
, p. 1796 - 1802 (2016/11/18)
A simple protocol for the preparation of functionalized allylic amines under mild, transition-metal-free conditions from the reaction of Morita–Baylis–Hillman (MBH) bromides with amines is described herein. The treatment of the MBH bromides with various amines in the presence of NaI and Et3N in aqueous acetone solution and at room temperature affords the corresponding functionalized allyl amines in moderate to good yields (45–87%). The reaction is rapid and carried out at room temperature.
