Regioselective Transformation of Malic Acid: A Practical Method for the Construction of Enantiomerically Pure Indolizidines

Gmeiner, Peter; Junge, D.

doi:10.1021/jo00117a052

Cited by 21 publications

(20 citation statements)

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“…Compound 6b 20 (50 mg, 0.26 mmol) was reacted as described for compound 6a to afford 44 mg (82%) of 7b after chromatographic purification (1:9 EtOAc/Hex): [α] D 20 = + 64.6 ( c 1.2, CHCl 3 ); 1 H NMR (CDCl 3 ) δ 7.35–7.26 (m, 5H), 4.81–4.77 (m, 2H), 4.58 (s, 2H), 3.95–3.73 (m, 3H), 3.73–3.62 (m, 2H), 1.98-1.91 (m, 2H); 13 C NMR (CDCl 3 ) δ 138.3, 128.3, 127.5, 126.2, 94.9, 75.8, 70.7, 68.8, 62.6, 35.0.…”

Section: Methodsmentioning

confidence: 99%

Flexible Cyclic Ethers/Polyethers as Novel P2-Ligands for HIV-1 Protease Inhibitors: Design, Synthesis, Biological Evaluation, and Protein−Ligand X-ray Studies

et al. 2008

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We report the design, synthesis and biological evaluation of a series of novel HIV-1 protease inhibitors. The inhibitors incorporate stereochemically defined flexible cyclic ethers/polyethers as the high affinity P2-ligands. Inhibitors containing small ring 1,3-dioxacycloalkanes have shown potent enzyme inhibitory and antiviral activity. Inhibitors 3d and 3h are the most active inhibitors. Inhibitor 3d maintains excellent potency against a variety of multi-PI-resistant clinical strains. Our structure-activity studies indicate that the ring size, stereochemistry, and position of oxygens are important for the observed activity. Optically active synthesis of 1,3-dioxepan-5-ol along with the syntheses of various cyclic ether and polyether ligands have been described. A protein-ligand X-ray crystal structure of 3d-bound HIV-1 protease was determined. The structure revealed that the P2-ligand makes extensive interactions including hydrogen bonding with the protease backbone in the S2-site. In addition, the P2-ligand in 3d forms a unique water-mediated interaction with the NH of Gly-48.

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Section: Methodsmentioning

confidence: 99%

Flexible Cyclic Ethers/Polyethers as Novel P2-Ligands for HIV-1 Protease Inhibitors: Design, Synthesis, Biological Evaluation, and Protein−Ligand X-ray Studies

et al. 2008

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“…Collidine hydrochloride was dried prior to use by gentle heating under vacuum. The following compounds were purchased, prepared according to literature procedures, or have already been described in the literature: 1 ,28 2 ,28 3 ,29 7 ,14 8 ,16 9 ,16 10 ,17 13, 15 ,30 16 ,31 18 ,32 19, 21, 23, 25 ,33 26 ,34 28 ,35 31 ,35 33 ,36 36 36…”

Section: Methodsmentioning

confidence: 99%

“…Synthesis of ( S )‐2 : Compound ( S )‐3 29 (981 mg, 5.0 mmol) was added in portions at −15 °C to a suspension of NaH (95 %, 264 mg, 10.5 mmol) in dry DMF (6 mL). After 10 min EtBr (1.19 g, 11.0 mmol) was added in DMF (6 mL) and the mixture was allowed to react for 14 h at room temperature.…”

Section: Methodsmentioning

confidence: 99%

Reagent‐Controlled Stereoselectivity in Titanocene‐Catalyzed Epoxide Openings: Reductions and Intermolecular Additions to α,β‐Unsaturated Carbonyl Compounds

Gansäuer

Bluhm

Rinker

et al. 2003

Chemistry A European J

112

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The generation and addition reactions of metal bound radicals derived from normal and meso epoxides by electron transfer from titanocene(III) reagents is described. The control of enantioselectivity and diastereoselectivity of these transformations is investigated by variation of the ligands of the metal complex. The reaction can lead to unprecedented and highly selective reactions, in which synthetically useful alcohols may be prepared. The synthesis presented also circumvents the use of toxic metals. Another advantage is that there is no loss of two functional groups as usually observed in reductive radical chain reactions.

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“…Different methods allow the access to this skeleton, such as intramolecular substitution of a halide [5] or a mesylate [6] by an amine, nucleophilic attack of an epoxide [7] or attack of an hydroxy ester [8] by an amine, and attack of a π-allyl palladium complex by an oxazolidinone [9] as well as an intra-Scheme 2 molecular Michael reaction [10] and radical cyclizations [11] . Allyl metals [12] , vinylsilanes [13] , and enolates [14] have been With the aim of obtaining nonracemic chiral 3-mesylpialso used to build up 3-hydroxylated piperidines. Thermal peridines, N-benzylprolinol (؊)-1 was treated with methreactions such as ene [15] or DielsϪAlder [16] reactions can anesulfonyl chloride in the presence of triethylamine in produce 3-hydroxypiperidines.…”

Section: Introductionmentioning

confidence: 99%

Ring Expansion – Formation of Optically Active 3-Hydroxypiperidines from Pyrrolidinemethanol Derivatives

Cossy¹,

Dumas²,

Pardo³

1999

Eur. J. Org. Chem.

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Treatment of pyrrolidinemethanol derivatives (–)‐1, (–)‐6, (–)‐7, 8, (–)‐9, (+)‐10, (–)‐11, and (–)‐21 with trifluoroacetic anhydride and then with Et3N afforded, after hydrolysis of the trifluoroacetyl group with NaOH, the optically active 3‐hydroxypiperidines (–)‐14, (+)‐15, (–)‐16, 17, (+)‐18, (–)‐19, (–)‐20, and (+)‐22, respectively. The yields are good and the enantiomeric excess excellent (up to 95 %).

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Regioselective Transformation of Malic Acid: A Practical Method for the Construction of Enantiomerically Pure Indolizidines

Cited by 21 publications

References 0 publications

Flexible Cyclic Ethers/Polyethers as Novel P2-Ligands for HIV-1 Protease Inhibitors: Design, Synthesis, Biological Evaluation, and Protein−Ligand X-ray Studies

Flexible Cyclic Ethers/Polyethers as Novel P2-Ligands for HIV-1 Protease Inhibitors: Design, Synthesis, Biological Evaluation, and Protein−Ligand X-ray Studies

Reagent‐Controlled Stereoselectivity in Titanocene‐Catalyzed Epoxide Openings: Reductions and Intermolecular Additions to α,β‐Unsaturated Carbonyl Compounds

Ring Expansion – Formation of Optically Active 3-Hydroxypiperidines from Pyrrolidinemethanol Derivatives

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