- Palladium-catalyzed asymmetric direct intermolecular allylation of α-aryl cyclic vinylogous esters: Divergent synthesis of (+)-oxomaritidine and (?)-mesembrine
-
We demonstrate that α-aryl cyclic vinylogous esters are competent substrates in the direct intermolecular Pd-catalyzed asymmetric allylic alkylation, enabling a straightforward enantioselective synthesis of 6-allyl-6-aryl-3-ethoxycyclohex-2-en-1-ones, common motifs embedded in numerous structurally diverse natural products. As an initial demonstration of the utility of this protocol, the first catalytic enantioselective total synthesis of (+)-oxomaritidine and an improved five-step catalytic enantioselective synthesis of (?)-mesembrine have been completed divergently.
- Wang, Wei,Dai, Jun,Yang, Qiqiong,Deng, Yu-Hua,Peng, Fangzhi,Shao, Zhihui
-
p. 920 - 924
(2021/02/16)
-
- Asymmetric Synthesis of Remote Quaternary Centers by Copper-Catalyzed Desymmetrization: An Enantioselective Total Synthesis of (+)-Mesembrine
-
Catalytic asymmetric syntheses of remote quaternary stereocenters have been developed by copper-catalyzed 1,4-hydrosilylation of ?,?-disubstituted cyclohexadienones. A variety of cyclohexenones have been synthesized in good yield and excellent enantioselectivity. Versatile 2-silyloxy diene intermediates bearing ?,?-disubstituted all carbon stereogenic centers can be isolated from the mild reaction conditions. The utility of this strategy is exemplified in a catalytic asymmetric total synthesis of (+)-mesembrine.
- Bokka, Apparao,Mao, James X.,Hartung, John,Martinez, Steven R.,Simanis, Justin A.,Nam, Kwangho,Jeon, Junha,Shen, Xiaoqiang
-
supporting information
p. 5158 - 5162
(2018/09/13)
-
- Diversity-Oriented Approach Toward the Syntheses of Amaryllidaceae Alkaloids via a Common Chiral Synthon
-
Functionalized hydroindole (1), a common chiral synthon, for versatile transformations to synthesize a broad range of Amaryllidaceae alkaloids (AAs) including (-)-crinine, (-)-crinane, (-)-amabiline, (+)-mesembrine, (-)-maritidine, (-)-oxomaritidine, and
- Verma, Prachi,Chandra, Atish,Pandey, Ganesh
-
p. 9968 - 9977
(2018/07/25)
-
- Total Synthesis of (+)-Mesembrine Applying Asymmetric Gold Catalysis
-
The total synthesis of enantiomerically pure (+)-mesembrine is described. The central pyrrolidine moiety incorporating a quaternary, all-carbon-substituted stereocenter was constructed employing an asymmetric gold-catalyzed cycloisomerization of a 1,4-diynamide.
- Spittler, Michael,Lutsenko, Kiril,Czekelius, Constantin
-
p. 6100 - 6105
(2016/07/26)
-
- A Concise Total Synthesis of (-)-Mesembrine
-
A concise total synthesis of mesembrine (four steps from known compound) was achieved both racemically and asymmetrically. Two key reactions were used here. One is the Rh(I)-catalyzed [5 + 1] cycloaddition of vinylcyclopropane 3c and CO. The other one is Buchwald's Pd-catalyzed coupling reaction that coupled β,γ-cyclohexenone 2c with aryl bromide 5 (using dppe ligand for racemic or (S)-Antphos ligand for asymmetric synthesis) to give γ,γ-disubstituted α,β-cyclohexenone 1c. Finally, aza-Michael addition converted 1c to mesembrine.
- Wang, Lu-Ning,Cui, Qi,Yu, Zhi-Xiang
-
p. 10165 - 10171
(2016/11/17)
-
- Asymmetric Michael Addition Reaction of α-Aryl-Substituted Lactams Catalyzed by Chiral Quaternary Ammonium Salts Derived from Cinchona Alkaloids: A New Short Synthesis of (+)-Mesembrine
-
The enantioselective Michael addition reaction of α-aryl-substituted lactams with electron-deficient olefins was efficiently catalyzed using chiral quaternary ammonium salts derived from cinchona alkaloids. This method was highly useful for the construction of an all-carbon-substituted quaternary carbon stereogenic center at the α-position of lactams in good to high yields and with good enantiomeric excess and could be applied to the short synthesis of (+)-mesembrine.
- Nunokawa, Shiori,Minamisawa, Masamitsu,Nakano, Keiji,Ichikawa, Yoshiyasu,Kotsuki, Hiyoshizo
-
p. 2301 - 2305
(2015/09/28)
-
- Highly chemoselective aerobic oxidation of amino alcohols into amino carbonyl compounds
-
The direct oxidation of unprotected amino alcohols to their corresponding amino carbonyl compounds has often posed serious challenges in organic synthesis and has constrained chemists to adopting an indirect route, such as a protection/deprotection strategy, to attain their goal. Described herein is a highly chemoselective aerobic oxidation of unprotected amino alcohols to their amino carbonyl compounds in which 2-azaadamantane N-oxyl (AZADO)/copper catalysis is used. The catalytic system developed leads to the alcohol-selective oxidation of various unprotected amino alcohols, carrying a primary, secondary, or tertiary amino group, in good to high yield at ambient temperature with exposure to air, thus offering flexibility in the synthesis of nitrogen-containing compounds. Strong as an ox: The highly chemoselective aerobic oxidation of unprotected amino alcohols to their corresponding amino carbonyl compounds has been achieved by using 2-azaadamantane N-oxyl (AZADO)/copper catalysis. This catalytic system oxidizes not only alcohols with tertiary amino groups but also those with secondary and primary amines in good to high yield at ambient temperature in air. bpy=2,2-bipyridyl, DMAP=4-(N,N-dimethylamino)pyridine.
- Sasano, Yusuke,Nagasawa, Shota,Yamazaki, Mai,Shibuya, Masatoshi,Park, Jaiwook,Iwabuchi, Yoshiharu
-
supporting information
p. 3236 - 3240
(2014/04/03)
-
- Double reduction of cyclic aromatic sulfonamides: Synthesis of (+)-mesembrine and (+)-mesembranol
-
The synthesis of (+)-mesembrine (1) and (+)-mesembranol (2) has been achieved from the monoterpene (S)-(-)-perillyl alcohol. Key transformations include a diastereo- and regioselective Pd-mediated intramolecular Heck reaction, and a double reduction of the resultant cyclic sulfonamide, to afford the cis-3a-aryloctahydroindole skeleton.
- Geoghegan, Kimberly,Evans, Paul
-
p. 3410 - 3415
(2013/06/26)
-
- Consecutive sigmatropic rearrangements in the enantioselective total synthesis of (-)-joubertinamine and (-)-mesembrine
-
Joubertinamine and mesembrine are two related alkaloids isolated from Sceletium plants. From the perspective of chemical synthesis, the major challenge posed by joubertinamine and mesembrine is undoubtedly the construction of the benzylic quaternary stere
- Ilardi, Elizabeth A.,Isaacman, Michael J.,Qin, Ying-chuan,Shelly, Sommer A.,Zakarian, Armen
-
experimental part
p. 3261 - 3269
(2009/08/15)
-
- The enantioselective Birch-Cope sequence for the synthesis of carbocyclic quaternary stereocenters. Application to the synthesis of (+)-mesembrine
-
A synthetic technique for generating carbocyclic quaternary stereocenters with exceptionally high levels of enantioselectivity is described. A sequence of three reactions, enantioselective Birch reduction-allylation, enol ether hydrolysis, and Cope rearrangement, is used to stereoselectively generate chiral quaternary centers on a 2-cyclohexen-1-one ring. The products of the sequence are 4,4-disubstituted-2-carboxamide-2-cyclohexen-1-one structures which are versatile intermediates in complex natural product synthesis. An application of the sequence to the synthesis of (+)-mesembrine illustrates the utility of these intermediates.
- Paul, Tapas,Malachowski, William P.,Lee, Jisun
-
p. 4007 - 4010
(2007/10/03)
-
- Substituted urea-octatydroindols as antagonists of melanin concentrating hormone receptor 1 (MCH1R)
-
The invention relates to compounds of the general formula (I) wherein R0, R1, R2, R3, R4, R5, R6, R7, R8, R9, Ar, and X are as defined in the description, or a pharmaceutically acceptable salt, hydrates, geometrical isomers, racemates, tautomers, optical isomers, N-oxides and prodrug forms thereof. The compounds may be used for the treatment or prophylaxis of disorders related to the MCH1R receptor and for modulation of appetite. The invention also relates to such use as well as to pharmaceutical formulations comprising a compound of formula (I).
- -
-
Page/Page column 29
(2010/02/11)
-
- Opening of aryl-substituted epoxides to form quaternary stereogenic centers: Synthesis of (-)-mesembrine
-
Cycloalkanones are easily converted into aryl-substituted cyclic alkenes by the addition of an aryl Grignard reagent followed by dehydration. These alkenes are good substrates for asymmetric epoxidation. We have found that the addition of allylic and benzylic Grignard reagents can occur preferentially at the benzylic position of the derived epoxides to give the quaternary stereogenic center. This approach led to a short synthesis of the nanomolar serotonin re-uptake inhibitor (-)-mesembrine.
- Taber, Douglass F.,He, Yigang
-
p. 7711 - 7714
(2007/10/03)
-
- SUBSTITUTED UREA-OCTAHYDROINDOLS AS ANTAGONISTS OF MELANIN CONCENTRATING HORMONE RECEPTOR 1 (MCH1R)
-
The invention relates to compounds of the general formula (I). (I) wherein R1, R2, R3, R4, R5, R6, R7, R8, and X are as defined in the description, or pharmaceutically acceptable salts, hydrates, geometrical isomers, racemates, tautomers, optical isomers, N-oxides and prodrug forms thereof. The compounds may be used for the treatment or prophylaxis of disorders related to the MCH1R receptor and for modulation of appetite. The invention also relates to such use as well as to pharmaceutical formulations comprising a compound of formula (I).
- -
-
Page/Page column 18-19
(2010/02/11)
-
- Enantioselective construction of cyclic quaternary centers: (-)-mesembrine
-
The preparation of the crystalline amide 2 is reported. Conjugate addition to 2 proceeded with the expected high diastereocontrol to give 3. This set the stage for subsequent intramolecular alkylidene C-H insertion to give, after ozonolysis and aldol condensation, (-)-mesembrine 1. Amide 2 should be a useful chiron for the enantioselective construction of cyclic quaternary centers.
- Taber,Neubert
-
p. 143 - 147
(2007/10/03)
-
- First enantiocontrolled synthesis of sceletium alkaloid A-4: Determination of the absolute configuration
-
Sceletium A-4, a pyridine alkaloid isolated from the Sceletium species, has been synthesized for the first time in an enantiocontrolled manner along with (-)-mesembrine, an alkaloid isolated from the same plant, starting from a chiral cyclohexadienone synthon to determine the absolute configuration.
- Kamikubo, Takashi,Ogasawara, Kunio
-
p. 783 - 784
(2007/10/03)
-
- Asymmetric synthesis of sceletium alkaloids: (-)-Mesembrine, (+)- sceletium a-4, (+)-tortuosamine and (+)-N-formyltortuosamine
-
Three procedures for the transformation of achiral 1-(3,4- dimethoxyphenyl)cyclohexene into enantiomerically pure 2-(3,4- dimethoxyphenyl)cyclohex-2-en-1-o1 have been established at first. Utilizing the (-)-cyclohexenol thus obtained, the four titled Sceletium alkaloids have been synthesized in the natural enantiomeric forms.
- Yamada, Osamu,Ogasawara, Kunio
-
p. 7747 - 7750
(2007/10/03)
-
- A concise synthesis of (-)-mesembrine
-
(-)-Mesembrine 11 was synthesized in 7 steps, in 19.4% overall yield and with ee>95%. The key step of the sequence is a stereoselective alkylation reaction of dianion derived from C2 symmetric imidazolines allowing efficient formation of quaternary benzylic center. Chiral auxiliaries derived from (S,S)-1,2-diamino-1,2-diphenylethane 1a and (S,S)-1,2-diaminocyclohexane 1b were compared. This synthesis provided unambiguous correlation of the newly formed stereocenter.
- Dalko, Peter I.,Brun, Virginie,Langlois, Yves
-
p. 8979 - 8982
(2007/10/03)
-
- Asymmetric construction of a quaternary carbon center by tandem [4 + 2]/[3 + 2] cycloaddition of a nitroalkene. The total synthesis of (-)-mesembrine
-
An efficient, total synthesis of the Sceletium alkaloid (-)-mesembrine is accomplished in seven steps and 19% yield from a functionalized nitroalkene (itself prepared in six steps and 34% yield from ethyl 3-bromopropionate). The construction of the octahydroindole framework of mesembrine features a tandem inter [4 + 2]/intra [3 + 2] cycloaddition of a 2,2-disubstituted 1-nitroalkene and a chiral vinyl ether derived from (1R,2S)-2-(1-methyl-1-phenylethyl)cyclohexanol as the central strategic element. The two stereogenic centers of the natural product, which include a benzylic, quaternary center, were established in 26/1 selectivity in the tandem process.
- Denmark, Scott E.,Marcin, Lawrence R.
-
p. 1675 - 1686
(2007/10/03)
-
- Total syntheses of (-)-mesembrane and (-)-mesembrine via palladium-catalyzed enantioselective allylic substitution and zirconium-promoted cyclization
-
4-Arylhexahydroindole derivatives 5 were synthesized from 2-arylcyclohexenyl allylamine derivatives 4, which have a large protecting group on nitrogen, using zirconium-promoted cyclization. Reaction of 4e with Cp2ZrBu2, followed by treatment with MeMgBr and then O2, gave 2a in 63% yield by a one-pot reaction, since the approach of O2 to zirconium was prevented by the aryl group. The total syntheses of (+)-mesembrane and (+)-mesembrine were achieved starting from 2a. To synthesize these natural products in a chiral form, the starting allylamine derivative 24 (80% yield, 86% ee, recrystallized from MeOH, 99% ee with 79% recovery) was prepared from allyl carbonate 22a and N-tosylallylamine 23 using palladium-catalyzed asymmetric amination in the presence of (S)-BINAPO as a chiral ligand. (-)-Mesembrane and (-)-mesembrine were synthesized from this allylamine 24.
- Mori,Kuroda,Zhang,Sato
-
p. 3263 - 3270
(2007/10/03)
-
- A new route to enantiomerically pure 4,4-disubstituted cyclohex-2-en-1-ones: Asymmetric synthesis of (+)-mesembrine
-
Enantiomerically pure β,β-disubstituted vinyl sulfoxides undergo cycloaddition with dichloroketene to give β,β-disubstituted γ-lactones which are transformed into synthetically important 4,4-disubstituted cyclohex-2-enones in optically pure form. The present method is applied to the synthesis of enantiomerically pure (+)-mesembrine.
- Kosugi,Miura,Kanna,Uda
-
p. 1409 - 1412
(2007/10/02)
-
- Enantiospecific Construction of Quaternary Carbon Center via Intramolecular 1,3-Dipolar Cycloaddition. A New Route to Natural (-)-Mesembrine from (S)-O-Benzylglycidol
-
Thermolysis of the aziridine ester, obtained from (S)-O-benzylglycidol, afforded the pyrrolidine lactone bearing a quaternary carbon center stereo-specifically in a good yield via intramolecular cycloaddition of the 1,3-dipole.The adduct (11) could be converted into natural (-)-mesembrine, the major alkaloid of Sceletium namaquense, and its N-demethyl derivative via a 8 step sequence of reactions.
- Takano, Seiichi,Samizu, Kiyohiro,Ogasawara, Kunio
-
p. 1239 - 1242
(2007/10/02)
-
- ENANTIOSELECTIVE SYNTHESIS OF NATURAL MESEMBRINE USING (D)-MANNITOL AS A CHIRAL TEMPLATE, A MODEL STUDY FOR THE ENANTIOSELECTIVE SYNTHESIS OF THE AMARYLLIDACEAE ALKALOIDS
-
Enantioselective synthesis of (-)-mesembrine (1) has been achieved using (D)-mannitol with the intention of developing the enantioselective synthesis of the Amaryllidaceae alkaloids.
- Takano, Seiichi,Imamura, Yoko,Ogasawara, Kunio
-
p. 4479 - 4482
(2007/10/02)
-