Preparation and anticonvulsant activity of a series of functionalized .alpha.-aromatic and .alpha.-heteroaromatic amino acids

Kohn, Harold; Kn, Sawhney; P, LeGall; Jd, Conley; Dw, Robertson; Jd, Leander

doi:10.1021/jm00165a006

Cited by 56 publications

(97 citation statements)

References 1 publication

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…[70] Owing mainly to its occurrence in a group of highly effective glycopeptides, such as vancomycin, b-avoparcin, and chloropeptin I, [71] it has been one of the synthetically most investigated series of amino acids over the last two years. [72] An atom-efficient synthesis by transition metal catalyzed amidocarbonylation has until now proved elusive since the classical cobalt catalysts cannot be extended to the carbonylation of aldehydes without an a-H atom.…”

Section: Synthetic Applications Of Palladium-catalyzed Amidocarbonylamentioning

confidence: 99%

Amidocarbonylation—An Efficient Route to Amino Acid Derivatives

Beller¹,

Eckert²

2000

Angew. Chem. Int. Ed.

136

View full text Add to dashboard Cite

Atom efficient, multicomponent reactions that lead to high-value products from inexpensive starting materials are of both economic and ecological interest for industrial organic synthesis. alpha-Amino acids are amongst the most important compounds in chemistry and biology. As well as their biochemical significance as building blocks of peptides and proteins, alpha-amino acids are also becoming increasingly interesting as fine chemicals. Possibly one of the key reactions in the preparation of these compounds is transition metal catalyzed amidocarbonylation, where the alpha-amino acid framework is constructed in a single step from an aldehyde, an amide, and carbon monoxide. This article gives a current overview of transition metal catalyzed amidocarbonylation reactions used in the synthesis of alpha-amino acids derivatives. A classification and summary of the significant features of this three component reaction is first presented together, with an historical introduction. This section is followed by two sections on cobalt- and palladium-catalyzed amidocarbonylation. A discussion of the mechanism of each of the different amidocarbonylation variants form an introduction. Overviews on further synthetic development of the methodology, such as the domino reaction with an amidocarbonylation step and the expansion of the range of starting materials, form the main topics of both variants. The potential of the method is demonstrated with the help of examples of special synthetic utility (for example, the preparation of arylglycines). Finally, possibilities for future developments in transition metal catalyzed amidocarbonylation reactions are proposed on the basis of the current state of knowledge.

show abstract

Section: Synthetic Applications Of Palladium-catalyzed Amidocarbonylamentioning

confidence: 99%

Amidocarbonylation—An Efficient Route to Amino Acid Derivatives

Beller¹,

Eckert²

2000

Angew. Chem. Int. Ed.

136

View full text Add to dashboard Cite

show abstract

“…In this new series of compounds, two, 40 and 41, were the most active. Analogue 41's MES ED 50 was also determined to be 62.4 mg kg -1 but has notably longer-lasting effects (up to 6 h) and a TD 50 over 100 mg kg -1 . Patch clamp electrophysiology studies demonstrated significant tonic blockade of T-type calcium current by compounds 39-41 at 1mM.…”

Section: Hydroxyamidesmentioning

confidence: 99%

“…In the recent years, Kohn and coworkers have reported on the anticonvulsant activity of a series of functionalized amino acids [47][48][49][50][51][52][53][54][55][56][57][58][59][60][61] (FAA) 5 ( Fig. 6).…”

Section: Derivatives Of Amino Acidsmentioning

confidence: 99%

New Anticonvulsant Agents

Malawska

2005

CTMC

144

View full text Add to dashboard Cite

The search for antiepileptic compounds with more selective activity and lower toxicity continues to be an area of intensive investigation in medicinal chemistry. This review describes new anticonvulsant agents representing various structures for which the precise mechanism of action is still not known. Many of the compounds presented in this review have been tested according to the procedure established by the Antiepileptic Drug Development Program of the Epilepsy Branch of the National Institute of Neurological Disorders and Stroke, National Institute of Health, USA. The newer agents include sulfonamides, amino acids, amides (analogs of gamma-vinyl GABA, N-benzylamides, 2,6-dimethylanilides, carboxyamides, hydroxyamides, alkanoamides); heterocyclic agents ((arylalkyl)imidazoles, pyrrolidin-2,5-diones, lactams, semi- thiosemicarbazones, thiadiazoles, quinazolin-4(3H)-ones, 2,5-disubstituted 1,2,4-thadiazoles, xanthones, derivatives of isatin) and enaminones. These new structural classes of compounds can prove useful for the design of future targets and development of new drugs.

show abstract

“…Both 2e and 2d exhibited these potent anticonvulsant effects at doses much lower than those which produced neuromotor impairment on the horizontal screen (HS) test (46.0 and 50.5 mg/kg were the ED50 doses for 2c and 2d on the HS test).5 These findings prompted our investigation of the pharmacological activity of the racemic N-substituted a,adiamino acid derivatives (2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) (Table 1). The N-acyl derivatives (2-n) were evaluated to determine the effect of conversion of the basic C(a)-amino group in 2a-d to a neutral C(a)-carbamate (Ze, 2 0 , urea (2g-2i), thiourea (2j, 2k), amide (21,2n), or succinimide (2m) substituent on anticonvulsant activity.…”

Section: Introductionmentioning

confidence: 99%