Sequential Gold-Catalyzed Carbene Transfer/Ring Closure: Oxidative Cyclization of β-(2-Alkynylphenyl)-α,β-ynones to Indenofuranones

Tehshik P. Yoon of the University of Wisconsin uncovered (J. Am. Chem. Soc. 2009, 131, 14604) conditions for the crossed photodimerization of acyclic enones. Minoru Isobe of Nagoya University extended (Synlett 2009, 1157) conjugate addition–intramolecular epoxide opening to substrates such as 4, leading to the cyclobutane 6 with high diastereocontrol. In the course of a total synthesis of (+)-brefeldin A, Jinsung Tae of Yonsei University established (Synlett 2009, 1303) conditions for the trans-selective cyclization of 7 to 8. Cyclization with TiCl4 gave the alternative cis diastereomer. Several methods have been put forward for the conversion of carbohydrate derivatives to carbocycles. Yeun-Mi Tsai of the National Taiwan University found (Tetrahedron Lett . 2009, 50, 3805) that acyl silanes such as 9 cyclized efficiently under free radical conditions, leading to the silyl ether 10. Tanmaya Pathak of the Indian Institute of Technology, Kharagpur, developed (Eur. J. Org. Chem. 2009, 872) the tandem conjugate addition– intramolecular alkylation conversion of 11 to 13. Slawomir Jarosz of the Polish Academy of Sciences, Warsawza, observed (Heterocycles 2009, 80, 1303) that the oxime derived from 14 cyclized to 15. The cyclization was accelerated by high pressure. Cyclohexanes can also be prepared from carbohydrates. Tony K. M. Shing of the Chinese University of Hong Kong showed (Organic. Lett. 2009, 11, 5070) that the nitrile oxide derived from 16 cyclized to 17, that he carried on to (-)-gabosine O. John K. Gallos of the Aristotle University of Thessaloniki described (Tetrahedron Lett. 2009, 50, 6916) related work. Paul E. Floreancig of the University of Pittsburgh devised (Organic. Lett. 2009, 11, 3152) conditions for the oxidative cyclization of 18 to 19. Ring closure proceeded with high equatorial selectivity. Kou Hiroya of Tohoku University found (J. Org. Chem. 2009, 74, 6623) that the single oxygenated stereogenic center of 20 directed the dissolving metal reduction–enolate trapping, leading to 21. Similarly, Susumu Kobayashi of the Tokyo University of Science showed (Synlett 2009, 1605) that the oxygenated stereogenic centers of 22 set the alkylated centers of 23. Many marine organisms are able to carry out brominative and chlorinative polyolefin cyclizations.

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Oxidative cyclization of N-methyl-dopa by a fungal flavoenzyme of the amine oxidase family

Journal of Biological Chemistry ◽

10.1074/jbc.ra118.004227 ◽

2018 ◽

Vol 293 (44) ◽

pp. 17021-17032

Author(s):

Majd Lahham ◽

Tea Pavkov-Keller ◽

Michael Fuchs ◽

Johannes Niederhauser ◽

Gabriel Chalhoub ◽

...

Keyword(s):

Crystal Structure ◽

Amine Oxidase ◽

Oxidative Cyclization ◽

Ring Closure ◽

Hydroxyl Group ◽

Binding Modes ◽

Recombinant Production ◽

Methyl Dopa ◽

Berberine Bridge Enzyme ◽

Ring Structures

Flavin-dependent enzymes catalyze many oxidations, including formation of ring structures in natural products. The gene cluster for biosynthesis of fumisoquins, secondary metabolites structurally related to isoquinolines, in the filamentous fungus Aspergillus fumigatus harbors a gene that encodes a flavoprotein of the amine oxidase family, termed fsqB (fumisoquin biosynthesis gene B). This enzyme catalyzes an oxidative ring closure reaction that leads to the formation of isoquinoline products. This reaction is reminiscent of the oxidative cyclization reported for berberine bridge enzyme and tetrahydrocannabinol synthase. Despite these similarities, amine oxidases and berberine bridge enzyme–like enzymes possess distinct structural properties, prompting us to investigate the structure–function relationships of FsqB. Here, we report the recombinant production and purification of FsqB, elucidation of its crystal structure, and kinetic analysis employing five putative substrates. The crystal structure at 2.6 Å resolution revealed that FsqB is a member of the amine oxidase family with a covalently bound FAD cofactor. N-methyl-dopa was the best substrate for FsqB and was completely converted to the cyclic isoquinoline product. The absence of the meta-hydroxyl group, as e.g. in l-N-methyl-tyrosine, resulted in a 25-fold lower rate of reduction and the formation of the demethylated product l-tyrosine, instead of a cyclic product. Surprisingly, FsqB did not accept the d-stereoisomer of N-methyltyrosine, in contrast to N-methyl-dopa, for which both stereoisomers were oxidized with similar rates. On the basis of the crystal structure and docking calculations, we postulate a substrate-dependent population of distinct binding modes that rationalizes stereospecific oxidation in the FsqB active site.

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THE OXIDATION OF 3-(N-BENZYLACETAMIDO)-1,2-PROPANEDIOL TO N-BENZYLACETAMIDOACETALDEHYDE AND RING CLOSURE OF THE LATTER TO ISOQUINOLINEL

Canadian Journal of Chemistry ◽

10.1139/v55-042 ◽

1955 ◽

Vol 33 (2) ◽

pp. 365-374 ◽

Cited By ~ 2

Author(s):

Arlen W. Frank ◽

C. B. Purves

Keyword(s):

Acetyl Derivative ◽

Oxidative Cyclization ◽

Lead Tetraacetate ◽

Ring Closure ◽

Diethyl Acetal ◽

Sodium Metaperiodate

Fischer's synthesis of isoquinoline by the oxidative cyclization of benzylaminoacetaldehyde diethyl acetal with 20% oleum was found to give a yield of 8.5%, but his isolation of the intermediate aldehyde could not be repeated. The N-acetyl derivative, N-benzylacetamidoacetaldehyde, however, was synthesized as a somewhat unstable oil, b.p. 129–131° (0.12 mm.), and was cyclized in 7.5% yield to isoquinoline. This synthesis involved the hydrogenation of 3-benzylideneamino-1,2-propanediol to 3-benzylamino-1,2-propanediol, b.p. 152-155° (0.5 mm.); hydrochloride, m.p. 92–94.5°. The N-acetyl derivative, 3-(N-benzylacetamido)-1,2-propanediol, b.p. 188° (0.12 mm.), was then oxidized with sodium metaperiodate; the behavior of other intermediates in the synthesis toward periodate, and also lead tetraacetate, was studied. The following additional compounds were thought to be new: 3-veratrylideneamino-1,2-propanediol, m.p. 123–125°; 3-veratrylamino-1,2-propanediol, b.p. 207–214° (0.4 mm.); the hydrochloride, m.p. 151–152°; 3-(N-benzylacetamido)-1,2-diacetoxypropane, b.p. 196–199° (0.7 mm.), and N-benzylacetamidoacetaldehyde 2,4-dinitrophenylhydrazone, m.p. 315–316°.

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Mannich and Ring Closure

ChemSpider Synthetic Pages ◽

10.1039/sp516 ◽

2011 ◽

Author(s):

Baris Kiskan

Keyword(s):

Ring Closure

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General Cyclopropane Assembly via Enantioselective Redox-Active Carbene Transfer to Aliphatic Olefins

10.26434/chemrxiv.7436795 ◽

2018 ◽

Author(s):

Marc Montesinos-Magraner ◽

Matteo Costantini ◽

Rodrigo Ramirez-Contreras ◽

Michael E. Muratore ◽

Magnus J. Johansson ◽

...

Keyword(s):

Total Synthesis ◽

Asymmetric Synthesis ◽

Chemical Space ◽

Synthetic Approach ◽

Asymmetric Cyclopropanation ◽

Redox Active ◽

Wide Range ◽

Leaving Group ◽

Stereoelectronic Properties ◽

Carbene Transfer

Asymmetric cyclopropane synthesis currently requires bespoke strategies, methods, substrates and reagents, even when targeting similar compounds. This limits the speed and chemical space available for discovery campaigns. Here we introduce a practical and versatile diazocompound, and we demonstrate its performance in the first unified asymmetric synthesis of functionalized cyclopropanes. We found that the redox-active leaving group in this reagent enhances the reactivity and selectivity of geminal carbene transfer. This effect enabled the asymmetric cyclopropanation of a wide range of olefins including unactivated aliphatic alkenes, enabling the 3-step total synthesis of (–)-dictyopterene A. This unified synthetic approach delivers high enantioselectivities that are independent of the stereoelectronic properties of the functional groups transferred. Our results demonstrate that orthogonally-differentiated diazocompounds are viable and advantageous equivalents of single-carbon chirons<i>.</i>

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