Synthesis Of Cyclic Amino Acids Research Articles

Stereocontrol in the synthesis of cyclic amino acids: a new ligand for directed hydrogenation through hydrogen bonding.

A system for the directed hydrogenation of nitrogen heterocycles is described in which hydrogen is delivered cis to a hydroxymethyl group by a rhodium catalyst with a simple phosphine ligand. The chemistry is applied to the synthesis of the hygric acid moiety of lincomycin and the pipecolic acid moiety of Argatroban. A series of control experiments indicate that the stereoselectivity is a result of a combination of both coordination and hydrogen bonding.

Stereoselective synthesis of cyclic amino acidsvia asymmetric phase-transfer catalytic alkylation

An asymmetric synthesis of cyclic amino acids having piperidine and azepane core structures was realized starting from readily available glycine and alanine esters by combination of phase-transfer catalyzed asymmetric alkylation and subsequent reductive amination.

Synthesis of non-natural cyclic amino acids from available unsaturated tertiary amines

New approach is developed to the synthesis of cyclic amino acids derivatives. Unsaturated tertiary amines react with ethyl diazoacetate under the catalysis by copper catalyst Cu(F3acac)2 leading to the formation of products of [2,3]-sigmatropic rearrangement which via the metathesis of double bonds undergo a ring closure. The subsequent hydrogenation of compounds obtained furnished esters of 6- and 7-membered cyclic α-amino acids. Besides the racemic also optically active compounds were obtained, in particular, esters of (R)- and (S)-pipecolic acid.

Catalytic asymmetric synthesis of cyclic amino acids and alkaloid derivatives: application to (+)-dihydropinidine and Selfotel synthesis

An asymmetric synthesis of cyclic amino acids having piperidine and azepane core structures was realized starting from readily available glycine and alanine esters by combination of phase-transfer catalyzed asymmetric alkylation and subsequent reductive amination. Some of these key intermediates were successfully transformed to natural alkaloid dihydropinidine and N-methyl-D-aspartate (NMDA) antagonist Selfotel.

Asymmetric Intramolecular Conjugate Addition of Chiral Enolates <i>via</i> Nonequilibrium

Optically active alpha,alpha-disubstituted alpha-amino acids belong to an important class of unnatural amino acids. Since the synthesis of such amino acids involves the creation of a quaternary stereocenter, methods for their synthesis have been extensively studied. We have reported that N-t-butoxycarbonyl(Boc)-N-methoxymethyl(MOM)-amino acid derivatives undergo asymmetric alpha-alkylation in up to 93% ee. Original chiral information on an amino acid is preserved in axially chiral enolate intermediates, and thus asymmetric induction is achieved without the aid of external chiral sources (i.e., memory of chirality). Recently, we have reported a new protocol for the asymmetric cyclization of amino acid derivatives, which enables straightforward synthesis of cyclic amino acids with a tetrasubstituted carbon center from the usual alpha-amino acids in up to 98% ee. Here we report the asymmetric construction of highly substituted chiral nitrogen heterocycles via intramolecular conjugate addition of chiral enolates generated from N-Boc-N-alkylylamino acid derivatives. This method is applicable to the asymmetric construction of pyrrolidine, piperidine, tetrahydroisoquinoline, and indoline derivatives with contiguous quaternary and tertiary stereocenters.

Enzymatic synthesis of cyclic amino acids by N-methyl- l-amino acid dehydrogenase from Pseudomonas putida

A new enzymatic system for the synthesis of enantiomerically pure cyclic amino acids (CAA) from the corresponding diamino acids or racemic CAA is described. α,ω-Diamino acids were oxidized to α-keto acids with amino acid oxidases (AAO). The α-keto acids were spontaneously transformed into cyclic imino acids in the reaction medium. The resulting imines were reduced to the l-form CAA with N-methyl- l-amino acid dehydrogenase (NMAADH) from Pseudomonas putida ATCC12633 using NADPH as a cofactor. l-Form CAA were also obtained from racemic CAA using d-amino-acid oxidase and NMAADH. Using this method, a new compound [1,4]-thiazepane-3-carboxylic acid (Fig. 1) was synthesized from aminopropylcystein.

Use of hydrolases for the synthesis of cyclic amino acids

The synthesis of several cyclic amino acids that have all the necessary structural features to make them ideal scaffolds for use in medicinal chemistry is described. A key step in each synthesis is the use of hydrolase enzymes to define a chiral centre. In order to elaborate these building blocks into more complex molecules, crystallization and asymmetric hydrogenation were used to define further stereocentres.

ChemInform Abstract: Synthesis of N‐Heterocycles via Lactam‐Derived Ketene Aminal Phosphates. Asymmetric Synthesis of Cyclic Amino Acids.

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Synthesis of N-heterocycles via lactam-derived ketene aminal phosphates. Asymmetric synthesis of cyclic amino acids.

A variety of N-heterocycles can be synthesized from lactams via Pd0-catalyzed couplings of their corresponding enol phosphates.

Stereoselective synthesis of conformationally restricted analogues of aspartic and glutamic acids from endocyclic enecarbamates

The stereoselective synthesis of cyclic amino acids incorporating the core framework of aspartic acid and glutamic acids were accomplished from a common intermediate. Oxidative cleavage of an aza-bicyclic-dichlorocyclobutanone/pentanone with Me 2CuLi Ac 2O followed by ozonolysis furnished the amino acid derivatives in good overall yields in a three-step sequence. This protocol was also applied to the synthesis of a cis- β-amino acid and to the enantioselective construction of a chimeric amino acid incorporating the basic skeleton of four different naturally occurring amino acids into a single structure.

ChemInform Abstract: Ketene Dithioacetals as 1,3‐Dipolarophiles. Applications to the Synthesis of Cyclic Amino Acids.

AbstractThe unsaturated azides (VI) and (XVI), prepared from the bromo acid (I) or the lactol (XII) as outlined in the reaction scheme, undergo intramolecular cyclization to form the pyrrolines (VII) or (XVII).

Ketene dithioacetals as 1,3-dipolarophiles. Applications to the synthesis of cyclic amino acids

Intramolecular azide cycloaddition reactions of ketene dithioacetals provide a new route to cyclic amino acids and a stereoselective synthesis of (2S,3S,4R)-3,4-dihydroxyproline (14) based on this methodology is described.

The synthesis of cyclic amino acids from dialdehydes and nitroacetates.

The synthesis of cyclic amino acids from dialdehydes and nitroacetates.