Stereospecific Synthesis of (R)-Aminocarnitine (Emeriamine) Starting from (R)-Carnitine via Double Inversion of Configuration

Castagnani, Roberto; Angelis, Francesco De; Fusco, Enrico De; Giannessi, Fabio; Misiti, D.; Meloni, Domenico; Tinti, Maria Ornella

doi:10.1021/jo00130a039

Cited by 19 publications

(16 citation statements)

References 3 publications

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“…Instead, we found a more circuitous route adapted from preparation of 3-azido butyrate (Fig. 1) that involves nucleophilic opening of the transient b-lactone [17,18]. The alkynyl FAs 1c and 2c were readily prepared, although an initial attempt relying on basemediated reaction with propynyl bromide gave only moderate amounts of product plus many side products.…”

Section: Resultsmentioning

confidence: 99%

“…NMR spectra were recorded on either a Varian Associates (Walnut Creek, CA, USA) Gemini 200 MHz or Inova 400 MHz instrument and are referenced to Si(CH 3 ) 4 . LC-MS data were recorded on a Waters-Micromass (Milford, MA, USA) ZMD instrument with APCI, using either: 1. an elution gradient of 40:60 water-acetonitrile to 100% acetonitrile over 30 min (or minor variations on those conditions) on a 2.1 9 150 mm Waters Symmetry C 18 3.5 lm column; or 2. direct injection without an LC column.…”

Section: Generalmentioning

confidence: 99%

“…Synthesis of 3-Azidodecanoic Acid (2b) [17,18] A solution of methyl 3-hydroxydecanoate (1.2 g, 5.9 mmol) and p-toluene sulfonic acid (25 mg, 0.15 mmol) was heated to reflux in 30 mL 2-methyl-1-propanol (isobutanol) for 24 h. After removal of solvent, the material was purified by column chromatography in 4:1 hexaneethyl acetate (R f product 0.5, starting material 0.4). The isobutyl 3-hydroxydecanoate 3 thus obtained (1.37 g, 5.61 mmol, 94%) was dissolved in 10 mL dichloromethane and pyridine was added (1 mL) followed by methanesulfonyl chloride (0.96 g, 8.4 mmol).…”

Section: Synthesis Of 17-azido Stearic Acid (1b)mentioning

confidence: 99%

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Clickable Lipids: Azido and Alkynyl Fatty Acids and Triacylglycerols

Zerkowski

Núñez

Strahan

et al. 2009

J Americ Oil Chem Soc

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Hydroxy fatty acids (FAs), which were isolated from glycolipids that can be prepared fermentatively from fats and oils, have been synthetically modified to contain azide and alkyne functional groups. These particular functional groups were chosen because they can participate in a copper-catalyzed reaction that combines them to form a 1,4-triazole, known as a ''click'' reaction, which has been widely used in a variety of fields but remains underutilized in FA chemistry. Depending on the starting hydroxy FA, these groups can be close to the carboxy unit (using 3-hydroxydecanoate) and hence the polar glycerol group, or distant from it (using 17-hydroxyoctadecanoate). These structural alternatives will impart different properties to the triacylglycerols that are subsequently prepared from the modified FA. Finally, the click reaction was used to conjugate triacylglycerols to each other and to other molecules such as a glycolipid or a protected amine.

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Section: Resultsmentioning

confidence: 99%

Section: Generalmentioning

confidence: 99%

Section: Synthesis Of 17-azido Stearic Acid (1b)mentioning

confidence: 99%

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Clickable Lipids: Azido and Alkynyl Fatty Acids and Triacylglycerols

Zerkowski

Núñez

Strahan

et al. 2009

J Americ Oil Chem Soc

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“…A few years ago, we described an original synthesis of ( R )‐aminocarnitine starting from ( R )‐carnitine through a double inversion of configuration of the stereogenic center 4. Yields were good (49%) and the enantiomeric purity was complete.…”

Section: Methodsmentioning

confidence: 99%

A Practical and Stereoconservative Synthesis of (R)‐3‐Amino‐4‐(trimethylammonio)butanoate [(R)‐Aminocarnitine], and Its Trimethylphosphonium and Simple Ammonium Analogues Starting from D‐Aspartic Acid

et al. 2003

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We have developed a new stereospecific synthesis of (R)‐aminocarnitine using D‐aspartic acid as the starting material. This strategy, which is simple and amenable to an industrial scale‐up, gives the target compound in six steps and in fairly good overall yields (41%). Other aminocarnitine related molecules such as optically pure (R)‐3‐amino‐4‐(trimethylphosphonio)butanoic acid and (R)‐3,4‐diaminobutanoic acid dihydrochloride have also been prepared according to the same synthetic strategy. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

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“…However, the ester bond between carnitine and the spacer is pharmacokinetically unfavorable, as it is easily cleaved by esterases. We therefore chose the bioisosteric aminocarnitine as a targeting group [11]. The aminocarnitine was bound to the ketoamide inhibitors by an amide bond between its amino group and the terminal carboxylate of the α,ω -dicarboxylic acid spacers.…”

mentioning

confidence: 99%

Synthesis and Evaluation of Calpain Inhibitors Carrying Muscle Cell Targeting Groups

Weyermann¹,

Herzner²,

Lescop³

et al. 2006

LDDD

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Inhibition of the cysteine protease calpain is a promising strategy for the treatment of muscular dystrophies including Duchenne Muscular Dystrophy. For the treatment to be effective, uptake of the inhibitors into the muscle cells is a prerequisite. A series of α-ketoamide calpain inhibitors carrying various muscle cell targeting capping groups was synthesized. Compounds with charged or highly polar targeting groups were not able to cross the cellular membrane. Introduction of lipoic acid as end cap yielded cell permeable calpain inhibitors with nanomolar potency.

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Stereospecific Synthesis of (R)-Aminocarnitine (Emeriamine) Starting from (R)-Carnitine via Double Inversion of Configuration

Cited by 19 publications

References 3 publications

Clickable Lipids: Azido and Alkynyl Fatty Acids and Triacylglycerols

Clickable Lipids: Azido and Alkynyl Fatty Acids and Triacylglycerols

A Practical and Stereoconservative Synthesis of (R)‐3‐Amino‐4‐(trimethylammonio)butanoate [(R)‐Aminocarnitine], and Its Trimethylphosphonium and Simple Ammonium Analogues Starting from D‐Aspartic Acid

Synthesis and Evaluation of Calpain Inhibitors Carrying Muscle Cell Targeting Groups

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