33948-35-5Relevant academic research and scientific papers
Total Synthesis of Isodaphlongamine H: A Possible Biogenetic Conundrum
Chattopadhyay, Amit Kumar,Ly, Vu Linh,Jakkepally, Shashidhar,Berger, Gilles,Hanessian, Stephen
, p. 2577 - 2581 (2016)
Herein we describe the first synthetic efforts toward the total synthesis of isodaphlongamine H, a calyciphylline B-type alkaloid. The strategy employs a chemoenzymatic process for the preparation of a functionalized cyclopentanol with a quaternary center. This molecule is elaborated to form an enantiopure 1-aza-perhydrocyclopentalene core, representing rings A and E of all calyciphylline B-type alkaloids. Further transformations involve the formation of a cyclic enaminone, 1,4-conjugate addition with a cyclopentenyl subunit, and intramolecular aldol cyclization to achieve a pentacyclic intermediate, ultimately forming isodaphlongamine H in a total of 24 steps from the commercially available compound 2-carbethoxycyclopentanone. Isodaphlongamine H exhibits promising inhibitory activity against a panel of human cancer cell lines. The missing link? A concise and highly convergent total synthesis of isodaphlongamine H was accomplished in 24 linear steps. The molecule exhibited promising inhibitory activity against a panel of human cancer cell lines. PCC=pyridinium chlorochromate.
Enantiocomplementary Preparation of Optically Pure 2-Trimethylsilylethynyl-2-cyclopentenol by Homochiralization of Racemic Precursors: A New Route to the Key Intermediate of 1,25-Dihydroxycholecalciferol and Vincamine
Takano, Seiichi,Suzuki, Mahito,Ogasawara, Kunio
, p. 1043 - 1046 (1993)
Treatment of racemic 2-trimethylsilylethynyl-2-cyclopentenol with vinyl acetate in the presence of lipase PS in toluene yielded a 1 : 1 mixture of the unreacted (S)-alcohol and the (R)-acetate which without isolation afforded the chirally homogeneous (R)-alcohol in 73percent overall yield on reaction with acetic acid in the same reaction medium in the presence of diisopropyl azodicarboxylate and triphenylphosphine, followed by reductive deacylation of the resulting (R)-acetate .On the other hand, hydrolysis of the racemic acetate , obtained from , in a phosphate buffer solution in the presence of lipase PS yielded a 1 : 1 mixture of the (R)-alcohol and the unreacted (S)-acetate which without separation, furnished the enantiomerically homogeneous (S)-alcohol in 75percent overall yield on treatment with acetic acid under the above Mitsunobu conditions, followed by reductive deacylation of the resulting (S)-acetate .
Rhodium-Catalyzed [4+3] Cycloaddition to Furans: Direct Access to Functionalized Bicyclo[5.3.0]decane Derivatives
Krainz, Tanja,Chow, Sharon,Korica, Natasa,Bernhardt, Paul V.,Boyle, Glen M.,Parsons, Peter G.,Davies, Huw M. L.,Williams, Craig M.
, p. 41 - 44 (2016)
An efficient method to directly access the bicyclo[5.3.0]decane core was achieved by rhodium-catalyzed reaction of a novel donor-acceptor cyclopentenyl diazocarboxylate with a variety of furans. As this motif is commonly found within bioactive antitumor natural products, selected systems were further manipulated and evaluated against cancer cell lines sensitive to protein kinase C (PKC) activation. A cyclic donor-acceptor diazo compound was synthesized for the first time, facilitating direct access to the bicyclo[5.3.0]decane motif, which is commonly seen in a number of prominent natural products active against cancer. Some examples were evaluated against various PKC cancer cell lines.
Diastereoselective Synthesis of Planar Chiral Phosphoramidites with a Ferrocenophane Scaffold
Neel, Mathilde,Retailleau, Pascal,Voituriez, Arnaud,Marinetti, Angela
, p. 797 - 801 (2018)
A new family of planar chiral phosphoramidites with a [3]ferrocenophane structure was synthesized. The synthetic strategy involved diastereoselective formation of the chiral ferrocene units from suitable substituted bis-cyclopentadienyl derivatives. Preliminary coordination studies of these ligands were undertaken with the synthesis of palladium and platinum complexes.
Enantioselective Synthesis of All-Carbon Quaternary Centers Structurally Related to Amaryllidaceae Alkaloids
Miku?ek, Ji?í,Jansa, Petr,Jagtap, Pratap R.,Va?í?ek, Tomá?,Císa?ová, Ivana,Matou?ová, Eli?ka
, p. 10069 - 10072 (2018)
Enantioselective synthesis of all-carbon quaternary centers remains a considerable challenge for synthetic organic chemists. Here, we report a two-step protocol to synthesize such centers including tandem cyclization/Suzuki cross-coupling followed by halocarbocyclization. During this process, two rings, three new C?C bonds and a stereochemically defined all-carbon quaternary center are formed. The absolute configuration of this center is controlled by the stereochemistry of the adjacent stereocenter, which derives from an appropriate enantioenriched starting material. Using this method, we synthesized polycyclic compounds structurally similar to Amaryllidaceae alkaloids in high enantiomeric excesses. Because these products resemble naturally occurring compounds, our protocol can be used to synthesize various potentially bioactive compounds.
The development and scope of a versatile tandem Stille-oxa-electrocyclization reaction
Tambar, Uttam K.,Kano, Taichi,Zepernick, John F.,Stoltz, Brian M.
, p. 345 - 350 (2007)
A palladium-catalyzed tandem Stille-oxa-electrocyclization reaction has been developed for the convergent preparation of highly substituted polycyclic pyran systems. The strategy presented in this letter is an alternative to the known methods for construc
Aqueous chemoenzymatic one-pot enantioselective synthesis of tertiary α-aryl cycloketonesviaPd-catalyzed C-C formation and enzymatic C=C asymmetric hydrogenation
Luan, Pengqian,Liu, Yunting,Li, Yongxing,Chen, Ran,Huang, Chen,Gao, Jing,Hollmann, Frank,Jiang, Yanjun
supporting information, p. 1960 - 1964 (2021/03/26)
An aqueous chemoenzymatic cascade reaction combining Pd-catalyzed C-C formation and enzymatic C=C asymmetric hydrogenation (AH) was developed for enantioselective synthesis of tertiary α-aryl cycloketones in good yields and excellent enantioselectivities. The stereopreference of the enzyme in AH of α-aryl cyclohexenones was studied. An enantiocomplementary enzyme was obtained by site-directed mutation.
Tethered Counterion-Directed Catalysis: Merging the Chiral Ion-Pairing and Bifunctional Ligand Strategies in Enantioselective Gold(I) Catalysis
Frison, Gilles,Guinchard, Xavier,Marinetti, Angela,Retailleau, Pascal,Smal, Vitalii,Voituriez, Arnaud,Zhang, Zhenhao
supporting information, p. 3797 - 3805 (2020/03/10)
Tethering a metal complex to its phosphate counterion via a phosphine ligand enables a new strategy in asymmetric counteranion-directed catalysis (ACDC). A straightforward, scalable synthetic route gives access to the gold(I) complex of a phosphine displaying a chiral phosphoric acid function. The complex generates a catalytically active species with an unprecedented intramolecular relationship between the cationic Au(I) center and the phosphate counterion. The benefits of tethering the two functions of the catalyst are demonstrated here in a tandem cycloisomerization/nucleophilic addition reaction, by attaining high enantioselectivity levels (up to 97% ee) at an unusually low 0.2 mol % catalyst loading. Remarkably, the method is also compatible with a silver-free protocol.
Regio- and Stereoselective Allylic Substitutions of Chiral Secondary Alkylcopper Reagents: Total Synthesis of (+)-Lasiol, (+)-13-Norfaranal, and (+)-Faranal
Skotnitzki, Juri,Spessert, Lukas,Knochel, Paul
supporting information, p. 1509 - 1514 (2019/01/05)
Chiral secondary alkylcopper reagents were prepared from chiral secondary alkyl iodides by a retentive I/Li exchange followed by a retentive transmetalation with CuBr?P(OEt)3. Switching the solvent to THF significantly increased their configura
Discovery of Novel 1-Cyclopentenyl-3-phenylureas as Selective, Brain Penetrant, and Orally Bioavailable CXCR2 Antagonists
Lu, Hongfu,Yang, Ting,Xu, Zhongmiao,Lin, Xichen,Ding, Qian,Zhang, Yueting,Cai, Xin,Dong, Kelly,Gong, Sophie,Zhang, Wei,Patel, Metul,Copley, Royston C. B.,Xiang, Jianing,Guan, Xiaoming,Wren, Paul,Ren, Feng
supporting information, p. 2518 - 2532 (2018/03/26)
CXCR2 has emerged as a therapeutic target for not only peripheral inflammatory diseases but also neurological abnormalities in the central nervous system (CNS). Herein, we describe the discovery of a novel 1-cyclopentenyl-3-phenylurea series as potent and CNS penetrant CXCR2 antagonists. Extensive SAR studies, wherein molecules' property forecast index (PFI) was carefully optimized for overall balanced developability profiles, led to the discovery of the advanced lead compound 68 with a desirable PFI. Compound 68 demonstrated good in vitro pharmacology with excellent selectivity over CXCR1 and other chemokine receptors. Rat and dog pharmacokinetics (PK) revealed good oral bioavailability, high oral exposure, and desirable elimination half-life of the compound in both species. In addition, the compound demonstrated dose-dependent efficacy in the in vivo pharmacology neutrophil infiltration "air pouch" model in rodents after oral administration. Further, compound 68 is a CNS penetrant molecule with high unbound fraction in brain tissue.
