Enolate oxidation by sulfonyloxaziridines

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Enolate oxidation by sulfonyloxaziridines

Enolates can be oxidized by sulfonyloxaziridines.[1][2] The enolate reacts by nucleophilic displacement at the electron deficient oxygen of the oxaziridine ring.

Enolate oxidation by sulfonyloxaziridine

This reaction type is extended to asymmetric synthesis by the use of chiral oxaziridines derived from camphor (camphorsulfonyl oxaziridine). Each isomer gives exclusive access to one of the two possible enantiomers. This modification is applied in the Holton Taxol total synthesis.

two optical isomers of camphorsulfonyl oxaziridine

In the enolate oxidation of the cyclopentaenone below [3] with either camphor enantiomer the trans isomer is obtained because access for the hydroxyl group in the cis position is limited. The use of the standard oxaziridine did not result in an acyloin.

enolate oxidation example ref. Hughes 2005

References

  1. Synthesis of .alpha.-hydroxycarbonyl compounds (acyloins): direct oxidation of enolates using 2 sulfonyloxaziridines Franklin A. Davis, Lal C. Vishwakarma, Joanne G. Billmers, John Finn J. Org. Chem.; 1984; 49(17); 3241-3243. Abstract
  2. Asymmetric Oxidation of Ester and Amide Enolates Using New (Camphorylsulfony1)oxaziridines Davis, F. A.; Haque, M. S.; Ulatowski, T. G.; Towson, J. C. J. Org. Chem. 1986, 51, 2402. Abstract
  3. An Electrochemical Approach to the Guanacastepenes Chambers C. Hughes, Aubry K. Miller, and Dirk Trauner ORGANIC LETTERS 2005 Vol. 7, No. 16 3425-3428 Article

Silicon- Acyloin ring synthesis

Pfizer Announces Availability Of Quillivant XR™ (methylphenidate hydrochloride) CII For Extended-Release Oral Suspension In The United States

methyl phenyl(piperidin-2-yl)acetate

Methylphenidate (MPH; MPD) is a psychostimulant drug approved for treatment of ADHD or attention-deficit hyperactivity disorder, postural orthostatic tachycardia syndrome and narcolepsy. It is better known by its 1948 trademarked name of Ritalin (original owner CIBA, now Novartis Corporation), was first licensed by the FDA in 1955 for treating ADHD, prescribed from 1960, and became heavily prescribed in the 1990s, when ADHD itself became more widely accepted.[1]

ADHD and some other conditions are believed to be linked to sub-performance of the dopamine, norepinephrine, and glutamate processes in the brain responsible for self-regulation functions, leading to self-regulation disorders compromising the sufferer’s attention, self-control, behaviour, motivation, and executive function; methylphenidate primarily works by reducing the reuptake of dopamine and norepinephrine which improves the levels and utility of these neurotransmitters in the brain. Methylphenidate possesses some structural and pharmacological similarities to cocaine, though methylphenidate is less potent and longer in duration.[2][3][4]

January 14, 2013

Pfizer Inc.  today announced that Quillivant XR™ (methylphenidate hydrochloride) CII for extended-release oral suspension is now available in the U.S. for the treatment of attention deficit hyperactivity disorder (ADHD). Quillivant XR is the first once-daily, extended-release liquid methylphenidate for ADHD and is now available by prescription.

“We also recognize that caring for and treating a child with ADHD goes beyond medication. We look forward to working with mothers and other caregivers of children with ADHD to provide meaningful resources to the ADHD community.”

“In order to effectively treat patients with chronic conditions such as ADHD, it is important to consider individual patient needs, including options for medication administration,” said Ann Childress, M.D., president of the Center for Psychiatry and Behavioral Medicine, Las Vegas, who was an investigator in the Quillivant XR laboratory classroom study. “As the first once-daily, extended-release liquid medication for patients with ADHD, Quillivant XR represents a new alternative to other ADHD treatments.”

Quillivant XR was approved by the U.S. Food and Drug Administration (FDA) on September 27, 2012 for the treatment of ADHD in patients aged 6 years and above. The efficacy of Quillivant XR was evaluated in a randomized, double-blind, placebo-controlled, crossover, multicenter, laboratory classroom study of 45 children with ADHD. Quillivant XR significantly improved ADHD symptoms compared to placebo at the primary endpoint of four hours post-dose, and in a secondary analysis, showed significant improvement at every time point measured, from 45 minutes to 12 hours after dosing.

Chemistry

Four isomers of methylphenidate are known to exist. One pair of threo isomers and one pair of erythro are distinguished, from which only d-threo-methylphenidate exhibits the pharmacologically usually desired effects. When the drug was first introduced it was sold as a 3:1 mixture of erythro:threo diastereomers. The erythro diastereomers are also pressor amines. “TMP” is referring only to the threo product that does not contain any erythro diastereomers. Since the threo isomers are energetically favored, it is easy to epimerize out any of the undesired erythro isomers. The drug that contains only dextrorotary methylphenidate is called d-TMP. A review on the synthesis of enantiomerically pure (2R,2′R)-(+)-threo-methylphenidate hydrochloride has been published.

Methylphenidate preparation according to Jeffrey M. Axten et al. (1998)

Methylphenidate production

  1. http://www.ehow.com/about_5374709_ritalin-invented.html When Was Ritalin Invented?, citing Lawrence Diller: “Running on Ritalin”, 1999
  2.  “Ritalin & Cocaine: The Connection and the Controversy”. Learn.genetics.utah.edu. Retrieved on 2011-10-16.
  3. Mary Ann Boyd (2005). Psychiatric nursing: contemporary practice. Lippincott Williams & Wilkins. pp. 160–. ISBN 978-0-7817-4916-9. Retrieved 30 April 2011.
  4. Peter Doskoch (2002). “Why isn’t methylphenidate more addictive?”. NeuroPsychiatry Rev. 3 (1): 19. Archived from the original on 2009-03-30.

 

In-Situ Spectroscopic Detection of Active Surface Species in Asymmetric Heterogeneous Catalysis

Thumbnail image of graphical abstract
In-Situ Spectroscopic Detection of Active Surface Species in Asymmetric Heterogeneous Catalysis

Guillaume Goubert and Prof. Peter H. McBreen

Article first published online: 4 JAN 2013 | DOI: 10.1002/cctc.201200679

ChemCatChem

Current Issue:January 2013

Volume 5, Issue1

http://onlinelibrary.wiley.com/doi/10.1002/cctc.201200679/abstract

Maeda  and Baiker employed in situ modulation excitation IR spectroscopy to explore diastereomer formation between ketopantolactone and cinchonidine on a Pt/Al2O3 catalyst surface. They found evidence that a C9[BOND]OH⋅⋅⋅O[DOUBLE BOND]C bond participates in enantiodifferentiation in the heterogeneous asymmetric hydrogenation of ketopantolactone to pantolactone.

Iron-Catalyzed Synthesis of Cyclopropyl Halides

Thumbnail image of graphical abstract
Iron-Catalyzed Synthesis of Cyclopropyl Halides

ChemCatChem, Current Issue:January 2013

Volume 5, Issue 1

Sabine Grupe and Prof. Dr. Axel Jacobi von Wangelin

Article first published online: 4 JAN 2013 | DOI: 10.1002/cctc.201200740

Under a halo: Selective iron-catalyzed hydrodehalogenations of dibromo- and dichlorocyclopropanes are effectively realized with tBuMgCl as the reductant. The reactions proceed under mild conditions and exhibit superior selectivities to iron-free protocols, as no allenes are formed. The sequential combination of base-mediated dihalocyclopropanation and this mono-dehalogenation provides straightforward access to substituted monohalocyclopropanes.
the supporting info file gives syn and spectral properties

Facile Synthesis of Benzaldehyde-Functionalized Ionic Liquids and Their Flexible Functional Group Transformations

208128.sch.001

Facile Synthesis of Benzaldehyde-Functionalized Ionic Liquids and Their Flexible Functional Group Transformations

http://www.hindawi.com/journals/oci/2012/208128/

Organic Chemistry International
Volume 2012 (2012), Article ID 208128, 5 pages
doi:10.1155/2012/208128

Qiang Huang and Baozhong Zheng

Department of Materials Science and Engineering, Yunnan University, Kunming 650091, China

Three benzaldehyde-functionalized ionic liquids were readily synthesized by quaternization of N-alkylimidazole with benzaldehyde-functionalized alkyl bromides under microwave irradiation in good yield. These aldehyde-functionalized ionic liquids could easily be oxidized in the presence of H2O2/KOH or be reduced by NaBH4 leading to the formation of the corresponding carboxyl-functionalized ionic liquids or benzylic alcohol-functionalized ionic liquids. In addition, the condensations of these functionalized ones with hydrazine hydrate and with aniline under reductive amination conditions were demonstrated.

http://www.hindawi.com/journals/oci/2012/208128/

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Transition Metal Ions as Efficient Catalysts for Facile Ortho-Formylation of Phenols under Vilsmeier–Haack Conditions

289023.sch.002

organic chemistry international, v 2012

Volume 2012 (2012),
doi:10.1155/2012/289023

Transition Metal Ions as Efficient Catalysts for Facile Ortho-Formylation of Phenols under Vilsmeier–Haack Conditions

F. Aneesa,1 K. C. Rajanna,2 Y. Arun Kumar,1 and M. Arifuddin3

1Department of Chemistry, Muffakham Jah College of Engineering and Technology, Mount Pleasant, Banjara Hills, Hyderabad 500034, India
2Department of Chemistry, Osmania University, Hyderabad 500007, India
3National Institute of Pharmaceutical Education and Research (NIPER) Balanagar, Hyderabad 500037, India

Related topicshttp://www.hindawi.com/journals/oci/2012/289023/

Aromatic compounds (phenols), when treated with Vilsmeier Haack (V-H) reagent in the presence of transition metal ions such as Cu(II), Ni(II), Co(II), Cd(II), and Zn(II) under reflux conditions, afforded corresponding ortho-formyl derivatives in good yields. Under normal conditions the metal-ion-free V-H reactions are too sluggish and resulted in poor yields. This protocol provides highly regioselective formylation under a mild and efficient condition with simple workup.

Related topicshttp://www.hindawi.com/journals/oci/2012/289023/

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The Formal Total Synthesis of FR252921 – An Immunosuppressant

Abstract Image

The Formal Total Synthesis of FR252921 – An Immunosuppressant

European Journal of Organic Chemistry Volume 2013, Issue 2, pages 376–388, January 2013 J. S. Yadav and Sandip Sengupta

Article first published online: 15 NOV 2012 | DOI: 10.1002/ejoc.201201097

Related topicshttp://onlinelibrary.wiley.com/doi/10.1002/ejoc.201201097/abstract

The formal total synthesis of FR252921 is described. The key steps include the preparation of three fragments starting from 1,4-butanediol, (R)-malic acid, and prenol, respectively, followed by two consecutive peptide couplings of the three fragments.

AbstractClick on the mini-structures!

The formal total synthesis of FR252921 is described. The key steps include the preparation of three fragments starting from 1,4-butanediol, (R)-malic acid, and prenol, respectively, followed by two consecutive peptide couplings of the three fragments. Other key steps involve an allene-type rearrangement or enyne isomerization to install the triene moiety, a Seebach methylation, a Julia olefination to construct the trisubstituted diene unit, and an enzymatic resolution strategy to generate the C-18 stereocenter.

other articles of relevance

J Antibiot (Tokyo). 2003 Feb;56(2):62-7.

FR252921, a novel immunosuppressive agent isolated from Pseudomonas fluorescens no. 408813 II. In vitro property and mode of action.

Fujine KAbe F, Seki N, Ueda H, Hino M, Fujii T.

Source

Exploratory Research Laboratories, Fujisawa Pharmaceutical Co., Ltd., 5-2-3 Tokodai, Tsukuba, Ibaraki 300-2698, Japan. kiyotaga-fujine@po.fujisawa.co.jp

Abstract

A novel immunosuppressive agent, FR252921 was isolated from the cultured broth of a species of Pseudomonas fluorescens. We have shown that FR252921 inhibited splenic proliferation stimulated with LPS, insensitive to calcinuerin inhibitor. In this study, FR252921 was found to inhibit IL-2 and IL-12 production as well as proliferaion of splenocyte. Analysis of transcription activity revealed that FR252921 inhibited activating protein-1 (AP-1). Exposures of antigen presenting cells (APC) to FR252921 attenuated proliferation supplemented by naïve T cells. Further, FR252921 strongly suppressed splenic dendritic cell proliferation stimulated with LPS and anti-CD40 mAb, while it did not inhibit purified T cell activation, including CD154 expression and IL-2 production. These results suggest that APC is dominant target cell population.

Chemistry. 2009;15(14):3457-73. doi: 10.1002/chem.200802649.

Synthesis of two bioactive natural products: FR252921 and pseudotrienic acid B.

Amans D, Bellosta V, Cossy J.

Source

Laboratoire de Chimie Organique, ESPCI ParisTech, CNRS, 10 rue Vauquelin, 75231 Paris, France.

Abstract

Concise and highly convergent syntheses of the immunosuppressive agent FR252921 and the related antimicrobial natural product pseudotrienic acid B were achieved from a common intermediate by using optically active titanium complexes to control the configuration of the stereogenic centers, a highly stereo- and regioselective cross-metathesis to generate the triene moieties, and a Stille cross-coupling to install the dienic units.

Synthesis of a Promising Immunosuppressant:  FR252921

Dominique Amans , Véronique Bellosta , and Janine Cossy
Laboratoire de Chimie Organique, ESPCI, CNRS, 10 rue Vauquelin, 75231 Paris Cedex 05, France
Org. Lett., 2007, 9 (23), pp 4761–4764
DOI: 10.1021/ol702110k

Figure

Links

http://onlinelibrary.wiley.com/doi/10.1002/ejoc.201201097/abstract

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