A General Approach to the Asymmetric Synthesis of Unsaturated Lipidic α-Amino Acids. The First Synthesis of α-Aminoarachidonic Acid

Kokotos, George; Padrón, José M.; Martı́n, Tomás; Gibbons, W. A.; Martı́n, Victor S.

doi:10.1021/jo9715128

Cited by 86 publications

(75 citation statements)

References 17 publications

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“…We reported recently on new methodologies for the synthesis of saturated [11] and unsaturated [12,13] lipidic α-amino acids. Their derivatives, the lipidic 3-amino-1,2-diols, the lipidic 2-amino alcohols and the lipidic 1,2-diamines are sphingoid base analogs.…”

Section: Introductionmentioning

confidence: 99%

Cytotoxicity of sphingoid marine compound analogs in mono- and multilayered solid tumor cell cultures

Padrón

Peters

2005

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A subset of four synthetic sphingoid marine compound analogs was chosen from a preliminary in vitro cytotoxicity study for further analysis. The selected analogs were initially screened in monolayer cultures for their anticancer potential against a panel of eight human tumor cell lines, ovarian, colon and lung cancer, squamous cell carcinoma and leukemia producing IC50 values ranging from 1.5 to 6.9 microM. In a secondary screening, the sphingoid analogs were evaluated against multilayered postconfluent cultures of A2780 ovarian cancer and WiDr colon cancer cells. In this model, compounds 5 and 8 were the most active derivatives showing EC50 values in the range 25-32 microM. The performance of 5 and 8 against both cell lines was not dependent on the cell culture model as shown with resistance factor values in the range 8-12. Cell cycle studies in HL60 leukemia cells showed an arrest in G(0)/G1 at a low drug concentration (3 microM) but accumulation in S phase at a high drug concentration (9 microM). It can be concluded that the analogs showed a cell line independent activity, with an apparent selectivity against cells grown in more physiological three-dimensional condition compared to standard anticancer drugs.

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Section: Introductionmentioning

confidence: 99%

Cytotoxicity of sphingoid marine compound analogs in mono- and multilayered solid tumor cell cultures

Padrón

Peters

2005

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“…They are nonnatural α-amino acids with saturated or unsaturated long side chains and can be prepared by classical methods in racemic form. New methods for the enantiomeric synthesis of saturated (23) or unsaturated derivatives, like 2-aminoarachidonic acid (24), have been recently presented. 2-Aminododecanoic acid (9a) and 2-aminohexadecanoic acid (9b) were prepared as described in the literature (22) and deaminated by treatment with NaNO 2 under acidic conditions (Scheme 3).…”

Section: Resultsmentioning

confidence: 99%

Synthetic routes and lipase‐inhibiting activity of long‐chain α‐keto amides

Chiou

Verger

Kokotos

2001

Lipids

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Synthetic routes to primary and N-alkyl alpha-keto amides are presented in this paper. Primary alpha-keto amides may be prepared by using an aldehyde as starting material. Commercially available alpha-keto acids may be coupled in high yield with primary amines by the mixed carbonic anhydride method affording N-alkyl alpha-keto amides. Alternatively, N-alkyl alpha-keto amides may be prepared by coupling long-chain alpha-hydroxy acids with amino components, followed by oxidation with pyridinium dichromate or NaOCl in the presence of 4-acetamido-2,2,6,6-tetramethyl-1-piperidinyloxy free radical. The alpha-keto amide derivatives prepared according to these procedures were tested for their ability to form stable monomolecular films at the air/water interface. The inhibition of porcine pancreatic lipase by the alpha-keto amides, spread as mixed films with 1,2-dicaprin, was studied with the monolayer technique. Among the compounds tested in this study, methyl 2-[(2-ketododecanoyl)amino]hexadecanoate was shown to be the most potent inhibitor, causing a 50% decrease in lipase activity at a 0.09 molar fraction.

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“…In this case too, the nature of amino protection seems to be critical (Kokotos et al, 1998). (Weygand and Fritz, 1965) (a) (Faust et al, 1983) (a) (d) (Svete et al, 1994) (a) (David and Veyribres, 1970) (a) (Bold et al, 1990) (a) (Hoffmann and Zeiss, 1992) (Winkler and Burger, 1996) (a) (Burger et al, 1995) ( ) (a) (Ornstein et al, 1994) (Wernic et al, 1989) (a) (Bergmeier, 1993) (a) (Robl et al, 1995) (a) Synthesis of the aldehyde 1 is described in the experimental section.…”

Section: Fig 5 Direct Synthesis Of Aspartaldehyde From Aspartic Acidmentioning

confidence: 99%

Syntheses of optically active 2-amino-4-oxobutyric acid and N,O-protected derivatives

Meffre

1999

Amino Acids

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Strategies for the synthesis of optically active aspartaldehyde derivatives are reviewed. Most of them are using the chiral pool: allylglycine or naturally occurring homoserine, aspartic acid or methionine and side chain modifications. This will be developed in the first part. Some other original routes are also displayed in the second part. Different aspects of each strategy are discussed: the nature and number of steps, the problem of protecting groups, the price and availability of starting materials. Some synthetic applications of such interesting chiral synthons are shown in the last part.

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A General Approach to the Asymmetric Synthesis of Unsaturated Lipidic α-Amino Acids. The First Synthesis of α-Aminoarachidonic Acid

Cited by 86 publications

References 17 publications

Cytotoxicity of sphingoid marine compound analogs in mono- and multilayered solid tumor cell cultures

Cytotoxicity of sphingoid marine compound analogs in mono- and multilayered solid tumor cell cultures

Synthetic routes and lipase‐inhibiting activity of long‐chain α‐keto amides

Syntheses of optically active 2-amino-4-oxobutyric acid and N,O-protected derivatives

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