Synthesis of 3‐ and 4‐Hydroxy‐2‐aminocyclohexanecarboxylic Acids by Iodocyclization

Szakonyi, Zsolt; Gyónfalvi, Szilvia; Forró, Enikő; Hetényi, Anasztázia; Kimpe, Norbert De; Fülöp, Ferenc

doi:10.1002/ejoc.200500297

Cited by 32 publications

(19 citation statements)

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“…The reactions of the N-acylated amino esters 69a-c with N -iodo-(NIS) or N -bromosuccinimide (NBS) proceeded stereoselectively, furnishing the bicyclic 1,3-oxazinone (70) and 1,3-oxazine derivatives (73a,b, 74a,b). Iodooxazinone (70) and iodo-and bromooxazine (73a,b, 74a,b) derivatives were dehalogenated with Bu 3 SnH, resulting in compounds 71 and 75a,b, which were easily converted to the all-cis amino acid 76 and its bicyclic oxazinone derivative 72 (Scheme 13) [49].…”

Section: By Functionalization Of a Ring Double Bondmentioning

confidence: 99%

“…Dehalogenation and hydrolysis led to the corresponding 3-and 4-hydroxy--amino acids 90 and 7 6 (Scheme 16). By the iodolactone procedure, starting from the same -lactam 86, the all-cis-2-amino-3-hydroxycyclohexanecarboxylic acid 90 was obtained (Scheme 17)[49]. The syntheses of 3-hydroxyamino acid enantiomers (-)-90 and (+)-90 were carried out similarly as for the racemic compounds given in Scheme 17.An alternative route for the introduction of a hydroxy group on the cyclohexane skeleton of the alicyclic -amino acid derivative involves stereoselective epoxidation of the olefinic bond and subsequent regioselective opening of the oxirane ring of the resulting epoxides.…”

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confidence: 99%

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Syntheses of Hydroxylated Cyclic β-Amino Acid Derivatives

Palkó

Kiss²,

Fülöp

2005

CMC

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This review is intended to give a short summary of the developments in the field of natural and synthetic alicyclic and heterocyclic hydroxylated beta-amino acids and to focus on the main strategies that have been reported for their synthesis. Given the medicinal and biological significance of the hydroxylated beta-amino acids, an increasing volume of research is currently being directed toward regio-, stereo- and enantioselective access to this class of compounds.

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Section: By Functionalization Of a Ring Double Bondmentioning

confidence: 99%

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confidence: 99%

Syntheses of Hydroxylated Cyclic β-Amino Acid Derivatives

Palkó

Kiss²,

Fülöp

2005

CMC

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“…When subjected to the iodolactone procedure, the bicyclic b-lactam derived from 1,3-cyclohexadiene furnished all-cis-2-amino-3-hydroxycyclohexanecarboxylic acid (199), while application of the iodooxazine procedure led not only to the all-cis-2-amino-3-hydroxycyclohexanecarboxylic acid, but also to all-cis-2-amino-4-hydroxycyclohexanecarboxylic acid 190 [47]. …”

Section: Synthesis Of Functionalized Carbocyclic B-amino Acid Derivatmentioning

confidence: 99%

Synthesis of Carbocyclic β‐Amino Acids

Kiss

Forró

Fülöp

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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j367 acids was reviewed by our group in 2001 [1]; the present chapter highlights the chemistry of these compounds published since 2000, with the aim of offering the reader an insight into the most recent developments in this field. Synthesis of Carbocyclic b-Amino AcidsOwing to their significance, a number of methods have been developed for the synthesis of these conformationally restricted molecules in racemic and enantiomerically pure form. The largest groups of carbocyclic b-amino acids and the most intensively investigated are the fiveand six-membered derivatives. One main method of preparation consists of the amidation of 1,2-dicarboxylic anhydrides 4, followed by Hoffmann rearrangement of the resulting amide 5 to amino acid 7. The same starting material, the meso anhydride 4, undergoes partial hydrolysis, followed by the Curtius rearrangement, to give 2-aminocyclohexanecarboxylic acid 7 (Scheme 8.1) ([1] and references cited therein).A widely used method for the synthesis of carbocyclic b-amino acids is the transformation of cycloalkenes via the corresponding bicyclic b-lactams. The 1,2dipolar cycloaddition of chlorosulfonyl isocyanate (CSI) to cycloalkenes 8 led regioselectively to the cycloalkane-fused b-lactams 10, whose acidic hydrolysis resulted in lactam ring opening and formation of the carbocyclic b-amino acid hydrochlorides 11 (Scheme 8.2) ([1] and references cited therein). O O O NH 4 OH COOH CONH 2 1. ROH 2. HO 3. H COOR COOH Curtius degradation COOH NH 2 Hoffmann degradation NaOH, Br 2 1. SOCl 2 2. NaN 3 Dowex 4 5 6 7 Scheme 8.1 Synthesis of carbocyclic b-amino acids by Curtius and Hoffmann rearrangements. CSI NSO 2 Cl O H 2 O NH O HCl, RT COOH NH 2 HCl 8 9 10 11 Scheme 8.2 Synthesis of carbocyclic b-amino acids from b-lactams. 368j 8 Synthesis of Carbocyclic b-Amino Acids 15 16 18 17 16:17:18 = 95.5:1.7:2.8 KOtBu, tBuOH ∆, 3hScheme 8.4 Synthesis of 3-methylcispentacin derivatives by conjugate addition. Synthesis of Carbocyclic b-Amino Acids j369To prepare 3-methyltranspentacin, aminocarboxylate 17 was first obtained in a larger quantity from diastereoisomer 16 by epimerization on treatment with KOtBu in tBuOH; this afforded 17 in quantitative yield and a diastereomeric excess of 99%. N-Deprotection of 17, followed by ester hydrolysis, gave the desired 3-methyltranspentacin in 97% e.e. [9].By using this conjugate addition methodology, Davies et al. also prepared 5-substituted derivatives of cispentacin. The addition of lithium amide (S)-13 to 5-isopropyl-, 5-phenyl-, and 5-tert-butylcyclopentenecarboxylates proceeded with a high degree of selectivity, the major derivatives formed having the amine anti to the 5-alkyl group. N-Deprotection by hydrogenolysis, subsequent acid hydrolysis of the ester, and ion-exchange chromatography furnished 5-substituted cispentacin derivatives in 98% e.e. [10].The asymmetric synthesis of a series of functionalized derivatives was achieved by using amine conjugate addition processes. Four stereoisomers of 2-amino-5carboxymethylcyclopentanecarboxylate were prepared ...

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“…b-Amino acids are very attractive compounds because of their potential biological activity (e.g., icofungipens and cispentacin) [1][2][3] and their utility in synthetic chemistry, [4][5][6] and they are important constituents of natural products such as alkaloids, peptides, and b-lactam antibiotics. 7,8 b-Amino acids can be used as building blocks for the preparation of modified (unnatural) analogs of biologically active peptides.…”

Section: Introductionmentioning

confidence: 99%

The role of π‐acidic and π‐basic chiral stationary phases in the high‐performance liquid chromatographic enantioseparation of unusual β‐amino acids

et al. 2008

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The application of 3,5-dimethylphenyl-carbamoylated-beta-cyclodextrin (Cyclobond I 2000 DMP) and 2,6-dinitro-4-trifluoromethylphenyl-ether-beta-cyclodextrin-based (Cyclobond DNP) chiral stationary phases for the high-performance liquid chromatographic enantioseparation of unusual beta-amino acids is reported. The investigated amino acids were saturated or unsaturated alicyclic beta-3-homo-amino acids and bicyclic beta-amino acids. Prior to chromatographic analyses, all amino acids were transformed to N-3,5-dinitrobenzoyl- or N-3,5-dimethylbenzoyl form to ensure a pi-acidic or pi-basic function and to enhance the pi-acidic-pi-basic interactions between analytes and chiral selectors. Chromatographic results are given as retention, separation and resolution factors. The chromatographic conditions were varied to achieve optimal separation. The sequence of elution of the enantiomers was determined in some cases.

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Synthesis of 3‐ and 4‐Hydroxy‐2‐aminocyclohexanecarboxylic Acids by Iodocyclization

Cited by 32 publications

References 32 publications

Syntheses of Hydroxylated Cyclic β-Amino Acid Derivatives

Syntheses of Hydroxylated Cyclic β-Amino Acid Derivatives

Synthesis of Carbocyclic β‐Amino Acids

The role of π‐acidic and π‐basic chiral stationary phases in the high‐performance liquid chromatographic enantioseparation of unusual β‐amino acids

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