6026-86-4Relevant academic research and scientific papers
Biosynthesis of lipstatin. Incorporation of multiply deuterium-labeled (5Z,8Z)-tetradeca-5,8-dienoic acid and octanoic acid
Goese,Eisenreich,Kupfer,Stohler,Weber,Leuenberger,Bacher
, p. 4673 - 4678 (2001)
Fermentation experiments with Streptomyces toxytricini were performed using (5Z,8Z)-[10,11,12,12-2H]tetradeca-5,8-dienoic acid or a mixture of [2,2-2H2]- and [8,8,8-2H3]octanoic acid as supplements. 2H NMR and mass spectroscopy confirmed the incorporation of (5Z,8Z)-[10,11,12,12-2H]tetradeca-5,8-dienoic acid into the C13 side chain as well as into the C6 side chain of lipstatin. Moreover, deuterium was incorporated into the C6 side chain of lipstatin from the 8-position but not from the 2-position of octanoate. The data establish that the β-lactone moiety of lipstatin is formed by condensation of a C8 and a C14 fatty acid with a concomitant exchange of the H-2 atoms of the C8 fatty acid.
Enantioselective Total Synthesis of (+)-Heilonine
Cassaidy, Kyle J.,Rawal, Viresh H.
, p. 16394 - 16400 (2021/10/20)
Chemical transformations that rapidly and efficiently construct a high level of molecular complexity in a single step are perhaps the most valuable in total synthesis. Among such transformations is the transition metal catalyzed [2 + 2 + 2] cycloisomerization reaction, which forges three new C-C bonds and one or more rings in a single synthetic operation. We report here a strategy that leverages this transformation to open de novo access to the Veratrum family of alkaloids. The highly convergent approach described herein includes (i) the enantioselective synthesis of a diyne fragment containing the steroidal A/B rings, (ii) the asymmetric synthesis of a propargyl-substituted piperidinone (F ring) unit, (iii) the high-yielding union of the above fragments, and (iv) the intramolecular [2 + 2 + 2] cycloisomerization reaction of the resulting carbon framework to construct in a single step the remaining three rings (C/D/E) of the hexacyclic cevanine skeleton. Efficient late-stage maneuvers culminated in the first total synthesis of heilonine (1), achieved in 21 steps starting from ethyl vinyl ketone.
Cross-Selective Aza-Pinacol Coupling via Atom Transfer Catalysis
Nagib, David A.,Rafferty, Sean M.,Rutherford, Joy E.,Wang, Lu,Zhang, Lumin
supporting information, p. 5622 - 5628 (2021/05/07)
A cross-selective aza-pinacol coupling of aldehydes and imines has been developed to afford valuable β-amino alcohols. This strategy enables chemoselective conversion of aliphatic aldehydes to ketyl radicals, in the presence of more easily reduced imines and other functional groups. Upon carbonyl-specific activation by AcI, a photoinitiated Mn catalyst selectively reduces the resulting α-oxy iodide by an atom transfer mechanism. The ensuing ketyl radical selectively couples to imines, precluding homodimerization by a classical reductive approach. In this first example of reductive, ketyl coupling by atom transfer catalysis, Zn serves as a terminal reductant to facilitate Mn catalyst turnover. This new strategy also enables ketyl radical couplings to alkenes, alkynes, aldehydes, propellanes, and chiral imines.
Exploiting Synergistic Catalysis for an Ambient Temperature Photocycloaddition to Pyrazoles
Lakeland, Christopher P.,Watson, David W.,Harrity, Joseph P. A.
supporting information, p. 155 - 159 (2019/12/11)
Sydnone-based cycloaddition reactions are a versatile platform for pyrazole synthesis, however they operate under harsh conditions (high temperature and long reaction times). Herein we report a strategy that addresses this limitation utilizing the synergistic combination of organocatalysis and visible-light photocatalysis. This new approach proceeds under ambient conditions and with excellent levels of regiocontrol. Mechanistic studies suggest that photoactivation of sydnones, rather than enamines, is key to the successful implementation of this process.
Bisheterocycle substituted oxa-spiro derivative, and preparation method and medical application thereof
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Paragraph 0406-0408, (2020/09/23)
The invention relates to a bisheterocyclic substituted oxa-spiro derivative, and a preparation method and medical application thereof. Specifically, the invention discloses compounds of formula (I) and formula (II) or pharmaceutically acceptable salts, stereoisomers or solvates thereof, and a preparation method and application thereof. Each group in the formulas is as defined in the specificationand claims in detail.
Site-Selective 1,1-Difunctionalization of Unactivated Alkenes Enabled by Cationic Palladium Catalysis
Jeon, Jinwon,Ryu, Ho,Lee, Changseok,Cho, Dasol,Baik, Mu-Hyun,Hong, Sungwoo
, (2019/07/03)
A palladium(II)-catalyzed 1,1-difunctionalization of unactivated terminal and internal alkenes via addition of two nucleophiles was developed using a cationic palladium(II) complex. The palladacycle generated in situ as a result of a regioselective addition of a nucleophile to the alkene can readily undergo regioselective β-hydride elimination and migratory insertion with a cationic palladium catalyst. The resulting η3-π-allyl palladium(II) complex is the key intermediate that reacts with a second nucleophile to furnish the desired 1,1-difunctionalization of the alkene. Under the optimized reaction conditions, a wide range of indoles and anilines add to alkene units of 3-butenoic or 4-pentenoic acid derivatives to afford the synthetically useful γ,γ- or δ,δ-difunctionalized products with excellent regiocontrol. Furthermore, by employing internal hydroxyl or acid groups and external carbon nucleophiles, this transformation enables unsymmetric 1,1-difunctionalization to forge challenging and important oxo quaternary carbon centers. Combining experiments and DFT calculations on the mechanism of the reaction is investigated in detail.
Site-Selective 1,1-Difunctionalization of Unactivated Alkenes Enabled by Cationic Palladium Catalysis
Jeon, Jinwon,Ryu, Ho,Lee, Changseok,Cho, Dasol,Baik, Mu-Hyun,Hong, Sungwoo
, p. 10048 - 10059 (2019/07/04)
A palladium(II)-catalyzed 1,1-difunctionalization of unactivated terminal and internal alkenes via addition of two nucleophiles was developed using a cationic palladium(II) complex. The palladacycle generated in situ as a result of a regioselective addition of a nucleophile to the alkene can readily undergo regioselective β-hydride elimination and migratory insertion with a cationic palladium catalyst. The resulting η 3-π-allyl palladium(II) complex is the key intermediate that reacts with a second nucleophile to furnish the desired 1,1-difunctionalization of the alkene. Under the optimized reaction conditions, a wide range of indoles and anilines add to alkene units of 3-butenoic or 4-pentenoic acid derivatives to afford the synthetically useful γ,γ-or ?,?-difunctionalized products with excellent regiocontrol. Furthermore, by employing internal hydroxyl or acid groups and external carbon nucleophiles, this transformation enables unsymmetric 1,1-difunctionalization to forge challenging and important oxo quaternary carbon centers. Combining experiments and DFT calculations on the mechanism of the reaction is investigated in detail.
COMPOUNDS, SALTS THEREOF AND METHODS FOR TREATMENT OF DISEASES
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Paragraph 00311-00312, (2019/03/12)
The present disclosure relates to compounds according to Formula (I), treating diseases.
Asymmetric one-pot synthesis of five- and six-membered lactones via dynamic covalent kinetic resolution: Exploring the regio- and stereoselectivities of lipase
Xu, Jintao,Hu, Lei
supporting information, p. 868 - 871 (2019/02/24)
Cascade lipase-catalyzed lactonization has been applied to dynamic hemithioacetal formation, leading to efficient five- and six-membered lactone synthesis as well as chiral discrimination. Solvent-dependent regioselectivity was observed for the selective formation of 1,3-oxathiolan-5-one and γ-butyrolactone derivatives.
One-pot chemoenzymatic synthesis of trolline and tetrahydroisoquinoline analogues
Zhao, Jianxiong,Lichman, Benjamin R.,Ward, John M.,Hailes, Helen C.
, p. 1323 - 1326 (2018/02/14)
Chemoenzymatic reaction cascades can provide access to chiral compounds from low-cost starting materials in one pot. Here we describe one-pot asymmetric routes to tetrahydroisoquinoline alkaloids (THIAs) using the Pictet-Spenglerase norcoclaurine synthase (NCS) followed by a cyclisation, to give alkaloids with two new heterocyclic rings. These reactions operated with a high atom economy to generate THIAs in high yields.
