Über die Ester und Äther des synthetischen Vitamins A

Isler, O.; Ronco, Álvaro L.; Guex, W.; Hindley, N. C.; Huber, Walter; Dialer, K.; Kofler, M.

doi:10.1002/hlca.19490320218

Cited by 65 publications

(13 citation statements)

References 15 publications

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“…Early studies of the synthesis of vitamin A represent pioneering investigations of the use of allylic rearrangements in the natural products area. The sulfuric-acid-catalyzed rearrangement of one allylic alcohol to its more conjugated isomer was used in the original C 14 −aldehyde route to vitamin A. , Multiple allylic rearrangements are characteristic features of vitamin A synthesis. , Allylic transpositions of the oxygen functionality have found wide applications in many other natural product areas. − …”

Section: Introductionmentioning

confidence: 99%

1,3-Transposition of Allylic Alcohols Catalyzed by Methyltrioxorhenium

et al. 1998

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Methyltrioxorhenium (MTO) catalyzes the 1,3-transposition of allylic alcohols to generate the more stable isomer at equilibrium. The direction of the equilibrium is largely decided by the nature of the OH group, i.e., whether it is primary, secondary, or tertiary. In the case of aliphatic allylic alcohols, tertiary is preferred to secondary which is preferred to primary. For aromatic allyl alcohols, the more conjugated isomer predominates largely at equilibrium. Oxygen-18 labeling showed that the OH groups of the parent and product are the same. The reaction is first order with respect to both allyl alcohol and MTO but strongly inhibited by traces of water. Theoretical calculations suggest the same results in the case of aliphatic allyl alcohols, although aromatic allyl alcohols do not follow the predictions. Studies of deuterium-labeled substrates show a large equilibrium isotope effect (K = 1.20 ± 0.02). For isomeric allyl alcohols differing in the position of deuterium only, the isomer with the deuterium at the sp3center predominates at equilibrium. The effect of conjugation from a phenyl group appears to be less important since calculations suggest that the phenyl group is forced out of plane of the allylic π system. Disciplines Chemistry CommentsReprinted (adapted) Methyltrioxorhenium (MTO) catalyzes the 1,3-transposition of allylic alcohols to generate the more stable isomer at equilibrium. The direction of the equilibrium is largely decided by the nature of the OH group, i.e., whether it is primary, secondary, or tertiary. In the case of aliphatic allylic alcohols, tertiary is preferred to secondary which is preferred to primary. For aromatic allyl alcohols, the more conjugated isomer predominates largely at equilibrium. Oxygen-18 labeling showed that the OH groups of the parent and product are the same. The reaction is first order with respect to both allyl alcohol and MTO but strongly inhibited by traces of water. Theoretical calculations suggest the same results in the case of aliphatic allyl alcohols, although aromatic allyl alcohols do not follow the predictions. Studies of deuterium-labeled substrates show a large equilibrium isotope effect (K ) 1.20 ( 0.02). For isomeric allyl alcohols differing in the position of deuterium only, the isomer with the deuterium at the sp 3 center predominates at equilibrium. The effect of conjugation from a phenyl group appears to be less important since calculations suggest that the phenyl group is forced out of plane of the allylic π system.

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Section: Introductionmentioning

confidence: 99%

1,3-Transposition of Allylic Alcohols Catalyzed by Methyltrioxorhenium

et al. 1998

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“…A2E was prepared according to the literature (16). Retinol (17) and retinaldehyde (18) were prepared from retinyl acetate according to literature procedures. The structures of all synthesized compounds were verified using 1 H, 13 C NMR spectroscopy and/or MS. Animals-All animal protocols were approved by the Institutional Animal Care and Use Committee of Columbia University and complied with guidelines set forth by the Institute for Laboratory Animal Research (Guide for the Care and Use of Laboratory Animals).…”

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confidence: 99%

C20-D3-vitamin A Slows Lipofuscin Accumulation and Electrophysiological Retinal Degeneration in a Mouse Model of Stargardt Disease

Kaufman

Zhang

et al. 2011

Journal of Biological Chemistry

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Autosomal recessive Stargardt disease (STGD1) is a macular dystrophy resulting from mutations in the ABCA4 (ABCR) gene. The age of onset of Stargardt disease is typically 10 -20 years of age and leads in almost all cases to blindness by age 50 (1, 2). A hallmark of the disease is premature lipofuscin accumulation in the retinal pigment epithelium (RPE) 2 of the eye. The RPE is critical for the neurosensory retina homeostasis; it acts as a transport exchange system with blood capillaries and is critical for regeneration and phagocytosis of photoreceptor outer segments. It is hypothesized that when RPE lipofuscin reaches a critical level, it contributes to a decline in cell function (3-8) resulting in the degeneration of the macular region of the neurosensory retina leading to loss of central vision (9 -11).The defective gene in Stargardt, ABCA4, encodes for an outer segment rim protein (RmP). The function of RmP is to transport the all-trans-retinaldehyde-phosphatidylethanolamine (retinaldehyde-PE) Schiff base from the luminal side of the disk membrane to the cytosolic face, where retinaldehyde can then be converted back to retinol (3). In the absence of its proper transporter, the retinaldehyde-PE conjugates may react to form vitamin A dimers (A2E and ATR-dimer among others), which are then deposited in the RPE after phagocytosis of the photoreceptors outer segments. Numerous studies have demonstrated the toxicity of vitamin A dimers to cultured RPE cells and they are hypothesized to play a key role in lipofuscin formation and subsequent retinal degeneration (12, 13). Nevertheless, the exact mechanisms that lead to lipofuscin accumulation or to vision loss as a result of the impaired transport of the retinaldehyde-PE conjugates remain unclear.In the accompanying article, we have shown that the ratedetermining step in vitamin A dimerization is the cleavage of a C20 carbon-hydrogen bond of the retinaldehyde-PE Schiff base (14). Replacing the C20 hydrogen atoms of vitamin A with deuterium atoms (i.e. C20-D 3 -vitamin A) makes this bond harder to cleave and impedes vitamin A dimerization (14). In this study we sought to determine whether retarding the intrinsic reactivity of vitamin A to dimerize could slow lipofuscin formation in the RPE and delay changes associated with human Stargardt disease. To accomplish this we raised ABCA4 Ϫ/Ϫ mutant albino mice (the mouse model of human Stargardt's disease) on diets containing either C20-D 3 -vitamin A (the treated group) or vitamin A at its natural isotopic abundance (the control group) and measured the concentration of vitamin A dimers, lipofuscin and other biological markers indicative of ocular health in both groups. Treated mice exhibited an 80% reduction in A2E, a 95% reduction in ATR dimer and a 70% decrease in fundus autofluorescence at three months of age. After six months, the treated group showed fewer lipofuscin granules as visualized qualitatively by electron microscopy, and at 12 months they showed improved eye function as measured by electroretinogram (ERG). ...

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“…Methyl vinyl ketone (MVK) is a versatile feeding stock in organic synthesis, for example, it is widely used as Michael acceptor in Robinson annulations and Baylis‐Hillman reactions, and also in the synthesis of many natural products and drug molecules, [1] such as Biperiden, [1a] Caulersin, [1b] Vinclozolin [1c] and Vitamin A acetate [1d] . However, its flammability, high toxicity, and pungent odour bring trouble with transportation and storage.…”

Section: Methodsmentioning

confidence: 99%

Boron‐Catalyzed Dehydrative Friedel‐Crafts Alkylation of Arenes Using β‐Hydroxyl Ketone as MVK Precursor

et al. 2020

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Boron‐catalyzed environmentally benign dehydrative Friedel‐Crafts alkylation of indole/pyrrole and aniline derivatives with β‐hydroxyl ketones has been developed for the first time. This method provides an efficient and green replacement of toxic and unstable methyl vinyl ketone (MVK) by safer and cheaper β‐hydroxyl ketone. The reaction features easy operation, wide substrate scope and significantly, only water is formed as by‐product.

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Über die Ester und Äther des synthetischen Vitamins A

Cited by 65 publications

References 15 publications

1,3-Transposition of Allylic Alcohols Catalyzed by Methyltrioxorhenium

1,3-Transposition of Allylic Alcohols Catalyzed by Methyltrioxorhenium

C20-D3-vitamin A Slows Lipofuscin Accumulation and Electrophysiological Retinal Degeneration in a Mouse Model of Stargardt Disease

Boron‐Catalyzed Dehydrative Friedel‐Crafts Alkylation of Arenes Using β‐Hydroxyl Ketone as MVK Precursor

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