New Type of Asymmetric Cyclization to Optically Active Steroid CD Partial Structures

Eder, Ulrich; Sauer, Gerhard; Wiechert, Rudolf

doi:10.1002/anie.197104961

Cited by 1,033 publications

(353 citation statements)

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“…This effect minimizes the fraction of the monomeric compound that operates as the organocatalyst. To avoid this limitation we sought an organocatalytic function that operates through reversible formation of covalent bonds, such as the venerable proline-based catalysts (13)(14)(15). Insertion of proline itself requires extensive synthetic sequences, but creation of an imidazolidinone in the space between the recognition elements as in 2a could be contemplated in a single step-the same step that assembles the autocatalyst.…”

Section: Resultsmentioning

confidence: 99%

Autocatalysis and organocatalysis with synthetic structures

Kamioka

Ajami

Rebek

2009

Proc. Natl. Acad. Sci. U.S.A.

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The discovery of ribozymes led to the proposal of an RNA world, where a single type of molecule was supposedly capable of selfreplication and chemical catalysis. We show here that both autocatalysis and organocatalysis can be engineered into a synthetic structure. The compound is shown to selectively accelerate its own formation and catalyze either hydrogenation or nucleophilic addition to α,β-unsaturated aldehydes. The observed reactivity indicates that the components of a purported pre-RNA world conceivably include smaller organic molecules.imidazolidinone catalysis | self-replication | template effects S tudies of prebiotic chemistry raise questions concerning which functions came nearer the origin of life-genetics or metabolism (1). The discovery of the catalytic activity of ribozymes provided an answer in which both functions could be accounted for in an "RNA world" (2). Although no one doubted that RNA could carry genetic information, some 15 years lapsed before an RNA molecule was shown to self-replicate (3), and this type of catalysis has since been developed to an extraordinary level of efficiency (4). Short, self-complementary DNA strands were shown to selfreplicate in 1986 (5), and autocatalysis based on molecular recognition was found in simplified organic molecules (6) and even peptides (7). At the present time, many types of self-replicating structures are known (8). These systems function like their nucleic acid counterparts in that the self-complementary structures operate as templates for their own formation. However, unlike ribozymes, the synthetic self-replicating systems are not known to catalyze other chemical reactions. The wholly synthetic structures act as either organocatalysts or autocatalysts, but published evidence for both activities in a single molecule is limited (9). This research was undertaken to find molecules that could perform in both capacities, and we report here an imidazolidinone-based compound and its properties as a catalyst and autocatalyst. Results and DiscussionTo realize an autocatalytic/organocatalytic molecule, we made modifications in the structure of compound 1, a molecule that bears self-complementary hydrogen-bonding subunits-a diaminotriazine and cyclic imide-that allow for dimerization in noncompeting organic media (Fig. 1). The arrangement of these subunits in 1 was earlier shown to allow its action as an autocatalyst (10): It acts as a template for its own synthesis, gathering two subunits on its surface to facilitate the formation of the amide bond. The insertion of a functional group known to catalyze organic transformations into 1 was a prospect to be explored. We initially inserted a thiourea into the framework of 1 (11). Although the thiourea function is a widely used organocatalyst (12), its applications were limited in the present context: The same hydrogen bonding that accounts for the thiourea's activity requires the use of solvents that also lead to tight dimerization of the template. This effect minimizes the fraction of the monomeric compound t...

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Section: Resultsmentioning

confidence: 99%

Autocatalysis and organocatalysis with synthetic structures

Kamioka

Ajami

Rebek

2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Among such catalysts, L-proline is the only known natural organocatalyst; it has been shown to catalyze asymmetric aldol reactions (33)(34)(35), but only in organic solvents or boiling water (36), conditions that are impossible in living organisms. Therefore, although L-proline is present in nature, it probably cannot catalyze such reactions in vivo.…”

Section: Discussionmentioning

confidence: 99%

Natural low-molecular mass organic compounds with oxidase activity as organocatalysts

Nishiyama

Hashimoto

Kusakabe

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Organocatalysts, low-molecular mass organic compounds composed of nonmetallic elements, are often used in organic synthesis, but there have been no reports of organocatalysts of biological origin that function in vivo. Here, we report that actinorhodin (ACT), a natural product derived from Streptomyces coelicolor A3(2), acts as a biocatalyst. We purified ACT and assayed its catalytic activity in the oxidation of L-ascorbic acid and L-cysteine as substrates by analytical methods for enzymes. Our findings were as follows: (i) oxidation reactions producing H 2 O 2 proceeded upon addition of ACT to the reaction mixture; (ii) ACT was not consumed during the reactions; and (iii) a small amount (catalytic amount) of ACT consumed an excess amount of the substrates. Even at room temperature, atmospheric pressure, and neutral pH, ACT showed catalytic activity in aqueous solution, and ACT exhibited substrate specificity in the oxidation reactions. These findings reveal ACT to be an organocatalyst. ACT is known to show antibiotic activity, but its mechanism of action remains unknown. On the basis of our results, we propose that ACT kills bacteria by catalyzing the production of toxic levels of H 2 O 2 . We also screened various other natural products of bacterial, plant, and animal origins and found that several of the compounds exhibited catalytic activity, suggesting that living organisms produce and use these compounds as biocatalysts in nature.A catalyst is a substance that increases the rate of a chemical reaction but is not consumed in the reaction. Catalysts are classified as homogeneous or heterogeneous, and most of the major homogeneous catalysts are metal-containing catalysts. In general, enzymes and ribozymes, which are classified as homogeneous catalysts, are referred to as biocatalysts. Enzymes are large proteins that catalyze numerous reactions in living organisms whereas ribozymes are composed of RNA and are known to catalyze phosphoryl transfer reactions (involved in RNA selfsplicing), the formation of peptide bonds, and various other reactions (1-5). Organocatalysts, which are homogeneous catalysts, are low-molecular mass organic compounds derived from nonmetallic elements (e.g., carbon, oxygen, hydrogen, and nitrogen) (6). Organocatalysts are used in industry because they have the following advantages over metal-containing catalysts (7-10): (i) Organocatalysts exhibit catalytic activity under mild conditions (atmospheric pressure, room temperature, and neutral pH); (ii) disposal of depleted organocatalysts is inexpensive; (iii) environmental loads due to waste reaction mixtures containing organocatalysts are low; and (iv) the risk of product contamination by metal ions is low. Therefore, organocatalysts have been receiving much attention in the field of green chemistry (11).In our laboratory, we have been studying the metabolism of actinomycetes from both fundamental and applied points of view (12)(13)(14)(15). From Streptomyces, we discovered a previously unidentified enzyme, L-glutamate oxidase (EC 1.4.3...

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“…13 In general, the organocatalytic reactions of proline are critically determined by the nucleophilic-electrophilic and acid-base properties of the endocyclic secondary amine and the exocyclic carboxylic acid, the balance of which can be readily modulated by non-covalent interactions with ancillary molecules. 14 In this study, we utilise carbon nanostructures to tune the catalytic properties of proline in the Hajos-Parrish-Eder-Sauer-Wiechert (HPESW) reaction 15,16 and demonstrate for the first time the principle that the known non-covalent interactions of amino acids with carbon nanostructures can be harnessed to control the activity and selectivity of organocatalysts for chemical transformations.…”

Section: Introductionmentioning

confidence: 99%

The effects of interactions between proline and carbon nanostructures on organocatalysis in the Hajos–Parrish–Eder–Sauer–Wiechert reaction

Rance

Khlobystov

2014

Nanoscale

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A note on versions:The version presented here may differ from the published version or from the version of record. If you wish to cite this item you are advised to consult the publisher's version. Please see the repository url above for details on accessing the published version and note that access may require a subscription. The non-covalent interactions of S-(-)-proline with the surfaces of carbon nanostructures (fullerene, nanotubes and graphite) change the nucleophilic-electrophilic and acid-base properties of the amino acid, thus tuning its activity and selectivity in the organocatalytic HajosParrish-Eder-Sauer-Wiechert (HPESW) reaction. Whilst our spectroscopy and microscopy measurements show no permanent covalent bonding between S-(-)-proline and carbon nanostructures, a systematic investigation of the catalytic activity and selectivity of the organocatalyst in the HPESW reaction demonstrates a clear correlation between the pyramidalisation angle of carbon nanostructures and the catalytic properties of S-(-)-proline. Carbon nanostructures with larger pyramidalisation angles have a stronger interaction wit h the nitrogen atom lone pair of electrons of the organocatalyst, thereby simultaneously decreasing the nucleophilicity and increasing the acidity of the organocatalyst. These translate into lower conversion rates but higher selectivities towards the dehydrated product of Aldol addition.

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New Type of Asymmetric Cyclization to Optically Active Steroid CD Partial Structures

Cited by 1,033 publications

References 2 publications

Autocatalysis and organocatalysis with synthetic structures

Autocatalysis and organocatalysis with synthetic structures

Natural low-molecular mass organic compounds with oxidase activity as organocatalysts

The effects of interactions between proline and carbon nanostructures on organocatalysis in the Hajos–Parrish–Eder–Sauer–Wiechert reaction

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