An efficient synthesis and acylation of α-amino-β-keto-esters: Versatile intermediates in the synthesis of peptide mimetics.

Singh, Jasbir; Gordon, Thomas D.; Earley, William G.; Morgan, Barry A.

doi:10.1016/s0040-4039(00)60549-x

Cited by 42 publications

(24 citation statements)

References 4 publications

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“…General Remarks: Amino ketone 9 [14] and oxazoline 27 [26] were prepared by reported procedures. All chemicals were reagent grade and used as purchased.…”

Section: Methodsmentioning

confidence: 99%

“…[13] It started with the activation of the Boc-protected valine 8 as a mixed anhydride by treatment with isobutyl chloroformate and coupling to the keto ester 9 [14] at Ϫ20°C. The resulting amidoketone 10 was transformed into the imidazole 11 with methylamine in the presence of acetic acid in refluxing xylenes with azeotropic removal of water.…”

Section: Synthesismentioning

confidence: 99%

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Syntheses and Structures of Imidazole Analogues of Lissoclinum Cyclopeptides

Haberhauer

Röminger

2003

Eur J Org Chem

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The syntheses of the cyclic peptides 3−7, which contain imidazole units in their backbones and resemble naturally occurring marine cyclopeptides such as westiellamide and ascidiacyclamide, are described. Structural investigations on the trimer 3 reveal a molecular triangle conformation with all lone pairs of the imidazole nitrogen atoms and the hydrogen atoms of the secondary amides directed to the center of the macrocycle. The structures of the tetramers 4 and 6 display distorted molecular square conformations with the heterocycles (4) and the αCH groups (6) placed at the corners of the rectangle, respectively. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

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“…General Remarks: Amino ketone 9 [14] and oxazoline 27 [26] were prepared by reported procedures. All chemicals were reagent grade and used as purchased.…”

Section: Methodsmentioning

confidence: 99%

Section: Synthesismentioning

confidence: 99%

Syntheses and Structures of Imidazole Analogues of Lissoclinum Cyclopeptides

Haberhauer

Röminger

2003

Eur J Org Chem

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“…The required α-amino-β-keto ester hydrochlorides are readily available by the following five methods: (1) the acid hydrolysis of a 4-alkoxycarbonyloxazole derived from a carboxylic anhydride and isocyanoacetic acid ester, 74) (2) the formation of the oxime from a β-keto ester and its reduction, 75) (3) the base-mediated N-C acyl migration of a N-t-butoxycarbonyl-N-acylglycine ester and then acid deprotection, 76) (4) the acylation of the benzophenone ketimine derived from a glycine ester in the presence of a strong base followed by acid hydrolysis, 77) and (5) the acylation of a N-acylaminomalonic acid half ester followed by deprotection. 78) The anti-selective asymmetric hydrogenation was affected by the bulkiness of the C4 substituent.…”

Section: Ru-axially Chiral Phosphine Catalystsmentioning

confidence: 99%

Development of New Methods in Organic Synthesis and Their Applications to the Synthesis of Biologically Interesting Natural Products

Hamada

2012

CHEMICAL & PHARMACEUTICAL BULLETIN

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2,6-Dimethyl-9-Aryl-9-phosphabicyclo[3.3.1]nonanes (9-PBN and 9-NapBN) and the chiral diaminophosphine oxides (DIAPHOXs) derived from aspartic acid have been introduced as useful ligands and preligands, respectively, for transition metal-catalyzed asymmetric synthesis. anti-Selective asymmetric hydrogenation of α-amino-β-ketoesters using Ru-, Rh-, Ir-, and Ni-catalysts through dynamic kinetic resolution have been developed for the first time, producing efficiently important anti β-hydroxy-α-amino acids. The total synthesis of several biologically active natural products was achieved by use of the transition metal-catalyzed reaction using DIAPHOX, anti-selective asymmetric hydrogenation, and reactions developed by us. Synthesis of tangutorine, an antitumor indole alkaloid, has been enantioselectively achieved for the first time. Enantioselective synthesis of a martinelline chiral core was accomplished using the asymmetric tandem Michael-Aldol reaction as a key step developed by us. This synthesis represents the formal total synthesis of martinelline and martinellic acid. Papuamide B was synthesized through the elucidation of unknown stereostructures by using the anti-selective asymmetric hydrogenation and reactions developed by us.

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“…d 198.1, 198.0, 171.5, 171.5, 166.4, 166.3, 155.7, 80.1, 80.0, 62.9, 62.9, 59.0, 58.9, 53.3, 53.3, 37.4, 37.2, 28.0, 27.9, 24.6, 24.5, 15.9, 15 Singh had described an efficient route for the general synthesis in which the a-amino-b-keto-esters hydrochloride 10 was coupled with BOC-or CBZ-ptotected a-amino acids to provide the oxo-dipeptides 2 (Scheme 3) [8]. The a-amino-b-keto-ester hydrochlorides 10 were obtained through alkylation of the Schiff base of an a-amino-ester with acyl chloride and then acidification with hydrochloric acid.…”

Section: Methyl 2-{[(s)-2-(tert-butoxycarbonylamino)-3-ethylbutanoyl]mentioning

confidence: 99%

Synthesis of α-amino-β-keto-esters (β-oxodipeptides)

Chen

2008

Front. Chem. China

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The synthesis of a-amino-b-keto-esters (b-oxo dipeptides) was studied. Corresponding a-amino-b-ketoesters were prepared from BOC-(L)-Valine and BOC-(L)-isoleucine by coupling with (D,L)-threonine hydrochloride and oxidation with Dess-Martin periodinane (DMP) with a total yield of 48% and 38%, respectively.Keywords a-amino-b-keto-esters, dipeptide, oxidation, Dess-Martin Periodinane (DMP)In recent years, a wide variety of natural cyclopeptides characterized by an alternating sequence of oxazole and thiazole moieties have been isolated from marine sources, mainly sponges and ascidians. These compounds have usually been identified as secondary metabolites of marine organisms possessing good cytotoxicity and antibacterial activity. This has prompted many chemists to study the structure and synthesis of these compounds [1,2]. The imidazole unit plays a major role in the biological functions of many peptides and proteins. However, no cyclopeptides containing imidazole units have yet been found in nature. Thus, some recent studies focused on the synthesis of the imidazole analogs of cyclopeptides [3,4]. As the key segments of the cyclopeptides mentioned above, the syntheses of these 5-membered heterocyclic dipeptide mimetics 1 were studied by Gorden T D (Scheme 1) [5]. They found that a-amino-b-keto-esters (b-oxo-dipeptides) of general structure 2 are useful intermediates in the synthesis of oxazole 1a, thiazole 1b and imidazole 1c dipeptide mimetics through different synthetic routes.In this paper, a-amino-b-keto-esters are the synthetic target molecules. Amino ketones 3 and 4 were prepared from BOC-(L)-Valine 5 and BOC-(L)-isoleucine 6, which were coupled with (L)-threonine methyl ester hydrochloride 7 and the resulting secondary alcohols 8 and 9were then oxidized with the Dess-Martin periodinane (DMP) [6] giving 48% yield and 38% yield (Scheme 2). Experiments Apparatus and reagentsSpecific rotations were measured on a WZZ-3 polarimeter. Infrared spectra were obtained using a BIO-BAD EXALIBUR FTS3000 series FT-IR instrument. 1 H and 13 C-NMR spectra were recorded employing a Bruker AV360 instrument and chemical shifts (d) are in ppm relative to TMS used as internal standard. Mass spectra were recorded on a Finnigan MAT 95 spectrometer using fast atom bombardment (HR-FABMS). All chemicals and solvents were of analytical grade. All reactions were monitored by TLC using glass sheets coated with silica gel (type GF254, Qingdao Haiyang). Flash column chromatography was carried out using 200-300 mesh silica gel. The oxidant, DMP, was prepared according to reference [6].

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An efficient synthesis and acylation of α-amino-β-keto-esters: Versatile intermediates in the synthesis of peptide mimetics.

Cited by 42 publications

References 4 publications

Syntheses and Structures of Imidazole Analogues of Lissoclinum Cyclopeptides

Syntheses and Structures of Imidazole Analogues of Lissoclinum Cyclopeptides

Development of New Methods in Organic Synthesis and Their Applications to the Synthesis of Biologically Interesting Natural Products

Synthesis of α-amino-β-keto-esters (β-oxodipeptides)

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