The enantioselective synthesis of (-)-physostigmine via chiral sulfoxides

Marino, Joseph P.; Bogdan, S.; Kimura, K K

doi:10.1021/ja00040a013

Cited by 97 publications

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“…They reported that the size of the alkyl group on the sulfoxide positively correlates with the degree of asymmetric induction. [190] Lactonization of isopropyl indolyl sulfoxide 164, followed by desulfonylation and dechlorination, gave 165 (in good enantiomeric excess), which was then transformed into (À)-2 (Scheme 33).…”

Section: A C H T U N G T R E N N U N G [33]-sigmatropic Rearrangemenmentioning

confidence: 99%

“…Enantioselective synthesis of (À)-physostigmine (2). [190] a) Zn/CuCl, Cl 3 CCOCl, THF, 0 8C; b) nBu 3 SnH, AIBN, toluene, reflux, 37 % (2 steps), 70-75 % ee; c) HCO 2 H, then MeCO 2 CHO, 94 %; d) MeNH 2 , À30 8C to RT, then H 2 SO 4 cat., DMF, 115 8C, 68 %; e) BH 3 ·THF, 0 8C to reflux, 64 %; f) Ni-Raney (W2), THF, reflux; g) Na cat., MeNCO, 60 % (2 steps). AIBN = azobisisobutyronitrile; Scheme 34.…”

Section: A C H T U N G T R E N N U N G [33]-sigmatropic Rearrangemenmentioning

confidence: 99%

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Structure, Bioactivity and Synthesis of Natural Products with Hexahydropyrrolo[2,3‐b]indole

Ruiz-Sanchis

Savina

Alberício

et al. 2011

Chemistry A European J

445

199

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Research on natural products containing hexahydropyrrolo[2,3-b]indole (HPI) has dramatically increased during the past few years. Newly discovered natural products with complex structures and important biological activities have recently been isolated and synthesized. This review summarizes the structures, biological activities, and synthetic routes for natural compounds containing HPI, emphasizing the different strategies for assembling this motif. It covers a broad range of molecules, from small alkaloids to complex peptides.

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Section: A C H T U N G T R E N N U N G [33]-sigmatropic Rearrangemenmentioning

confidence: 99%

Section: A C H T U N G T R E N N U N G [33]-sigmatropic Rearrangemenmentioning

confidence: 99%

Structure, Bioactivity and Synthesis of Natural Products with Hexahydropyrrolo[2,3‐b]indole

Ruiz-Sanchis

Savina

Alberício

et al. 2011

Chemistry A European J

445

199

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“…We tentatively assign this as the (P) configuration shown because (+)- [5]-helicene has the (P) configuration (3 1 …”

Section: Me0mentioning

confidence: 98%

Kinetic resolution of sulfoxides with pendant acetoxy groups using cholesterol esterase: substrate mapping and an empirical rule for chiral phenols

Serreqi¹,

Kazlauskas²

1995

Can. J. Chem.

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Sulfoxides are valuable chiral auxiliaries because they direct the formation of carbon~arbon bonds. As a route to enantiomerically pure sulfoxides, we examined hydrolase-catalyzed kinetic resolution by hydrolysis of apendant acetoxy group. Screening hydrolases for the enantioselective hydrolysis of the acetate in 2-(methylsulfiny1)phenyl acetate, lb, identified cholesterol esterase (CE) as the most enantioselective enzyme. The enantiomeric ratio, E, ranged from 10 to 25, favoring the (R) configuration at sulfur. Competing chemical hydrolysis of l b caused the large range in the measured values of E. A small-scale (250 mg) resolution of (2)-l b yielded (S)-lb with >99% ee (1 1 % yield) after recrystallization. Changing the methyl substituent to phenyl or n-butyl did not significantly change the enantioselectivity (E = 10 and 15, respectively), but changing it to a chloromethyl substituent lowered the enantioselectivity slightly (E = 5). Changing the phenyl acetate to a naphthyl acetate (2-(phenylsulfiny1)phenyl acetate vs. 1-(phenylsulfiny1)-2-naphthyl acetate) increased the enantioselectivity from 10 to 19. In all cases CE favored the (R)-sulfoxide. To aid the design of new resolutions with CE, we propose an empirical rule that accounts for the observed enantiopreference of CE toward these 5 sulfoxides and 15 other chiral aryl acetates. This empirical rule uses both the size of the substituents and their conformational preferences to predict which enantiomer reacts faster.Key words: kinetic resolution, lipase, cholesterol esterase, sulfoxides, empirical rule, Resume : Les sulfoxydes sont des auxiliaires chiraux utiles parce qu'ils orientent la formation de liaisons carbone-carbone. Dans le but d'obtenir des sulfoxydes Cnantiomeriquement purs, on a examine la possibilitC d'utiliser une rtsolution cinCtique catalysCe par une hydrolase impliquant l'hydrolyse d'un groupe acCtoxy. Une Cvaluation des hydrolases pour leur capacitt a effectuer l'hydrolyse CnantiosClective de llacCtate de 2-(mCthylsulfinyl)phCnyle, lb, a permis d'identifier 13estCrase de cholestCro1 (CE) comme l'enzyme le plus CnantiosClectif. Le rapport CnantiomCrique, E, vane de 10 a 25 et il favorise la configuration (R) au niveau du soufre. L'hydrolyse chimique compCtitive du composC l b provoque les grandes variations observkes dans les valeurs mesurCes de E. Une rCsolution preparative 5 faible Cchelle (250 mg) du composC (2)-lb conduit, aprks recristallisation, au (S)-lb avec un ee >99% (rendement de 11%). Lorsqu'on change le substituant de mCthyle 2 phCnyle ou n-butylC, il n'y a pas de changement significatif d'CnantiosClectivitC (E = 10 et 15, respectivement); toutefois, si on le remplace par un chloromCthyle, 1'CnantiosClectivitC est 1Cgkrement diminuCe (E = 5). Si l'on remplace I'acttate de phCnyle par 1'acCtate de naphtyle (acCtate de 2-(phCnylsulfiny1)phtnyle vs. acetate de 1-(phCnylsulfiny1)-2-naphtyle) 1'CnantiosClectivitC passe de 10 a 19. Dans tous les cas, la CE favorise le (R)-sulfoxyde. Dans le but d'aider au dtveloppement de...

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“…For background to physostigmine and related marine natural products, see: Marino et al (1989Marino et al ( , 1992. For recent, related structural and synthetic studies, see: Pozza Silveira et al (2012); Silveira & Marino (2013).…”

Section: Related Literaturementioning

confidence: 99%

5-Benzyloxy-3-methyl-1-tosyl-1H-indole

Oliver

Noll

2013

Acta Cryst E

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The title compound, C23H21NO3S, represents one of the few examples of a 5-substituted indole with a toluenesulfonyl group bonded to the N atom. The benzyl group adopts a synclinal geometry with respect to the indole ring [dihedral angle = 59.95 (4)°], while the tolyl ring is oriented close to perpendicular to the indole ring, making a dihedral angle of 81.85 (3)°. The indole N atom exhibits a slight pyramidalization.

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The enantioselective synthesis of (-)-physostigmine via chiral sulfoxides

Cited by 97 publications

References 0 publications

Structure, Bioactivity and Synthesis of Natural Products with Hexahydropyrrolo[2,3‐b]indole

Structure, Bioactivity and Synthesis of Natural Products with Hexahydropyrrolo[2,3‐b]indole

Kinetic resolution of sulfoxides with pendant acetoxy groups using cholesterol esterase: substrate mapping and an empirical rule for chiral phenols

5-Benzyloxy-3-methyl-1-tosyl-1H-indole

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