- Scalable Total Synthesis of rac-Jungermannenones B and C
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Reported is the first scalable synthesis of rac-jungermannenones B and C starting from the commercially available and inexpensive geraniol in 10 and 9 steps, respectively. The unique jungermannenone framework is rapidly assembled by an unprecedented regio
- Liu, Weilong,Li, Houhua,Cai, Pei-Jun,Wang, Zhen,Yu, Zhi-Xiang,Lei, Xiaoguang
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- An enantiospecific polyene cyclization initiated by an enantiomerically pure bromonium ion
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Dimethylaluminum triflate-mediated activation of tetrafluorobenzoates of enantiomerically pure bromohydrins results in enantiospecific polyene cyclizations. The initiation of cyclization by enantiomerically pure bromonium ions and subsequent propagation i
- Braddock, D. Christopher,Marklew, Jared S.,Foote, Kevin M.,White, Andrew J. P.
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- Design, synthesis and anthelmintic activity of 7-keto-sempervirol analogues
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The plant-derived, diterpenoid 7-keto-sempervirol was recently reported to display moderate activity against larval stages of Schistosoma mansoni (IC50 = 19.1 μM) and Fasciola hepatica (IC50 = 17.7 μM), two related parasitic blood and liver flukes responsible for the neglected tropical diseases schistosomiasis and fascioliasis, respectively. Here, we aimed to increase the potency of 7-keto-sempervirol by total synthesis of 30 structural analogues. Subsequent screening of these new diterpenoids against juvenile and adult lifecycle stages of both parasites as well as the human HepG2 liver cell line and the bovine MDBK kidney cell line revealed structure-activity relationship trends. The most active analogue, 7d, displayed improved dual anthelmintic activity over 7-keto-sempervirol (IC50 ≈ 6 μM for larval blood flukes; IC50 ≈ 3 μM for juvenile liver flukes) and moderate selectivity (SI ≈ 4–5 for blood flukes, 8–13 for liver flukes compared to HepG2 and MDBK cells, respectively). Phenotypic studies using scanning electron microscopy revealed substantial tegumental alterations in both helminth species, supporting the hypothesis that the parasite surface is one of the main targets of this family of molecules. Further modifications of 7d could lead to greater potency and selectivity metrics resulting in a new class of broad-spectrum anthelmintic.
- Crusco, Alessandra,Bordoni, Cinzia,Chakroborty, Anand,Whatley, Kezia C.L.,Whiteland, Helen,Westwell, Andrew D.,Hoffmann, Karl F.
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supporting information
p. 87 - 100
(2018/05/07)
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- Enantioselective, Lewis Base-Catalyzed Sulfenocyclization of Polyenes
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A sulfenium-ion-initiated, catalytic, enantioselective polyene cyclization is described. Homogeranylarenes and ortho-geranylphenols undergo polycyclization in good yield, diastereoselectivity, and enantioselectivity. The stereodetermining step is the generation of an enantiomerically enriched thiiranium ion from a terminal alkene and a sulfenylating agent in the presence of a chiral Lewis basic catalyst. The use of hexafluoroisopropyl alcohol as the solvent is crucial to obtain good yields. The thioether moiety resulting from the reaction can be subsequently transformed into diverse oxygen and carbon functionality postcyclization. The utility of this method is demonstrated by the enantioselective syntheses of (+)-ferruginol and (+)-hinokiol.
- Tao, Zhonglin,Robb, Kevin A.,Zhao, Kuo,Denmark, Scott E.
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supporting information
p. 3569 - 3573
(2018/03/21)
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- Alkyldisulfanium salts: Isolable, electrophilic sulfur reagents competent for polyene cyclizations
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Tools that can effect electrophilic sulfur-promoted cation-π cyclizations are generally lacking, especially using alkylsulfide-based reagents. Herein we report that combining three different 1,2-dithioethers with Cl2 and SbCl5 generates isolable alkyldisulfanium salts that can effect such reactions. These new reagents can install -SMe, -SEt, and -SCH2CH2CF3 in modest, moderate, or good yield on diverse frameworks, including polyenes that terminate with electron-deficient groups. We also show that reagents such as dimethyl(methylthio)sulfonium tetrafluoroborate (DMTSF) can accomplish similar chemistry.
- Schevenels, Florian T.,Shen, Minxing,Snyder, Scott A.
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- Et2SBr.SbCl5Br: An effective reagent for direct bromonium-induced polyene cyclizations
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It's all about reactivity: Although bromonium-induced cation-π cyclizations are commonly utilized by nature to fashion six-membered rings from a diverse set of polyene precursors, no general laboratory method exists that can achieve the same breadth of substrate scope. An easily synthesized and handled reagent is described (see scheme) that is capable of directly, broadly, and rapidly effecting such reactions in good yield with a variety of geraniol, farnesol, and nerol derivatives.
- Snyder, Scott A.,Treitler, Daniel S.
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supporting information; experimental part
p. 7899 - 7903
(2010/04/02)
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- Indium tribromide-promoted arene-terminated epoxy olefin cyclization
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An arene-terminated epoxy olefin cyclization was promoted by a water-tolerant Lewis acid to give tri- and tetracyclic 3β-hydroxy terpenoids and steroid derivatives in 57 and 37% yields, respectively, per new formed ring up to 75%. The Royal Society of Chemistry.
- Zhao, Jun-Feng,Zhao, Yu-Jun,Loh, Teck-Peng
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p. 1353 - 1355
(2008/12/21)
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- Ru(III)-Catalyzed Cyclization of Arene-Alkene Substrates via Intramolecular Electrophilic Hydroarylation
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(Matrix presented) We herein report that RuCl3/AgOTf has proven to be a hydroarylation catalyst with an efficiency and scope superior to previously known methods. This catalyst demonstrated consistent performance with arene-ene substrates of diverse structural features, providing good to excellent yields of cyclization products (chromanes, tetralins, terpenoids, dihydrocoumarins).
- Youn, So Won,Pastine, Stefan J.,Sames, Dalibor
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p. 581 - 584
(2007/10/03)
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- Regioselective palladium-catalyzed alkylation of allylic halides with benzylic Grignard reagents. Two-step synthesis of abietane terpenes and tetracyclic polyprenoid compounds
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A highly regioselective palladium-catalyzed α-alkylation of allylic bromides 1a,c-e and chloride 1b with substituted and unsubstituted benzylic Grignard reagents is reported. The resulting alltrans polyenehomobenzene derivatives were obtained in excellent yields and regioselectivity. These products were easily converted to abietane-type diterpenes (10-12) and tetracyclic polyprenoid compounds (13, 14) through a Lewis acid-promoted cascade polyene cyclization reaction.
- Rosales, Viale,Zambrano, Jorge L.,Demuth, Martin
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p. 1167 - 1170
(2007/10/03)
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- Enantio- and diastereoselective stepwise cyclization of polyprenoids induced by chiral and achiral LBAs. A new entry to (-)-ambrox, (+)-podocarpa-8,11,13-triene diterpenoids, and (-)-tetracyclic polyprenoid of sedimentary origin
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An enantio- and diastereoselective stepwise cyclization of polyprenoids induced by Lewis acid-assisted chiral Bronsted acids (chiral LBAs) and achiral LBAs is described. In particular, the absolute stereocontrol in the initial cyclization of polyprenoids to form an A-ring induced by chiral LBAs and the importance of the nucleophilicity of the internal terminator in polyprenoids for the relative stereocontrol in subsequent cyclization are demonstrated. (-)-Ambrox was synthesized via the enantioselective cyclization of (E,E)-homofarnesyl triethyrsily ether with triethylsilyl ether with tin(IV) chloride-coordinated (R)-2-(o-fluorobenzyloxy)-2′-hydroxy-1,1′-binaphthyl ((R)-BINOL-o-FBn) and subsequent diastereoselective cyclization with CF3CO2H·SnCl4 as key steps. Protection of (E,E)-homofarnesol by a triethylsilyl group increased the enantioselectivity of chiral LBA-induced cyclization and both the chemical yield and diastereoselectivity in the subsequent cyclization. The enantioselective cyclization of homo(polyprenyl)arenes possessing an aryl group was also induced by (R)-BINOL-o-FBn·SnCl4. Several optically active podocarpa-8,11,13-triene diterpenoids and (-)-tetracyclic polyprenoid of sedimentary origin were synthesized (75-80% ee) by the enantioselective cyclization of homo(polyprenyl)benzene derivatives induced by (R)-BINOL-o-FBn·SnCl4 and subsequent diastereoselective cyclization induced by BF3-Et2O/EtNO2 or CF3CO2H·SnCl4.
- Ishihara, Kazuaki,Ishibashi, Hideaki,Yamamoto, Hisashi
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p. 3647 - 3655
(2007/10/03)
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- Cyclisation Reactions: Part VI - Further Study in Biogenetic-type Cyclisation of Epoxy-Olefins
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(6E)-9-p-Methoxyphenyl-2,6-dimethylnona-2,6-diene (I) on mono-epoxidation affords mainly 2,3-epoxyolefin (IV) admixed with some 6,7-isomer.IV on cyclisation with boron trifluoride etherate furnishes three ketones: 7-oxo-9-p-methoxyphenyl-2,6-dimethylnon-2-ene (XIII) presumably formed from 6,7-epoxyolefin (XII), cis-3-(2-p-methoxyphenylethyl)-2,2,4-trimethylcyclohexanone (XIV) arising out of 1,4-hydride transfer in an intermediate cyclohexyl cation (XVII), and cis-3-(2-p-methoxyphenylethyl)-2,3,4-trimethylcyclohexanone (XV) resulting from three consecutive 1,2-H, Me shifts in the same intermediate.In addition, 12-methoxypodocarpa-8,11,13-trien-3β-ol (IX) is obtained in 10 percent yield.The mono-epoxide (V) from the corresponding 3-isopropyl-4-methoxyphenyldiene (II) on similar cyclisation affords, among others, hinokiol methyl ether (X) and another crystalline compound characterised by PMR and MS as 12-methoxy-13-isopropyl-A-homo-4a-oxapodocarpa-8,11,13-trien-3β-ol (XXII).The latter is formed by a concerted cyclisation of the di-epoxide (XXI) present in the starting material.Contrary to a previous report from this laboratory, it is now found that trans-podocarpa-8,11,13-trienes (XXV) are more stable than the cis-isomers and are almost the sole products of cyclisation of 2-(2-arylethyl)-1,3,3-trimethylcyclohexyl cations (XXIV) and their analogues under thermodynamically controlled condition.
- Nasipuri, Dhanonjoy,Samaddar, Ashis K.,Das, Gautam
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p. 727 - 734
(2007/10/02)
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