Asymmetric dipolar cycloaddition reactions: a practical, convergent synthesis of chiral pyrrolidines

Ma, Zhenkun; Wang, Sanyi; Cooper, Curt S.; Fung, Anthony K. L.; Lynch, John K.; Plagge, Frederick; Chu, Daniel T. W.

doi:10.1016/s0957-4166(97)00049-9

Cited by 64 publications

(34 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…␤ 2 -iso-Proline, a cyclic ␤ 2 -amino acid, is a potent agonist at the strychnine-sensitive glycine receptor. 231 It serves as a building block for the preparation of novel inhibitors of bacterial DNA gyrase 232 and forms the central moiety of a conformationally restricted, SCHEME 42 Solid-support asymmetric synthesis of ␤ 2 -homoarylglycines according to Calmès.…”

Section: Scheme 41mentioning

confidence: 99%

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

2004

View full text Add to dashboard Cite

Although they are less abundant than their alpha-analogues, beta-amino acids occur in nature both in free form and bound to peptides. Oligomers composed exclusively of beta-amino acids (so-called beta-peptides) might be the most thoroughly investigated peptidomimetics. Beside the facts that they are stable to metabolism, exhibit slow microbial degradation, and are inherently stable to proteases and peptidases, they fold into well-ordered secondary structures consisting of helices, turns, and sheets. In this respect, the most intriguing effects have been observed when beta2-amino acids are present in the beta-peptide backbone. This review gives an overview of the occurrence and importance of beta2-amino acids in nature, placing emphasis on the metabolic pathways of beta-aminoisobutyric acid (beta-Aib) and the appearance of beta2-amino acids as secondary metabolites or as components of more complex natural products, such as peptides, depsipeptides, lactones, and alkaloids. In addition, a compilation of the syntheses of both achiral and chiral beta2-amino acids is presented. While there are numerous routes to achiral beta2-amino acids, their EPC synthesis is currently the subject of many investigations. These include the diastereoselective alkylation and Mannich-type reactions of cyclic- or acyclic beta-homoglycine derivatives containing chiral auxiliaries, the Curtius degradation, the employment of transition-metal catalyzed reactions such as enantioselective hydrogenations, reductions, C-H insertions, and Michael-type additions, and the resolution of rac. beta2-amino acids, as well as several miscellaneous methods. In the last part of the review, the importance of beta2-amino acids in the formation of beta-peptide secondary structures is discussed.

show abstract

Section: Scheme 41mentioning

confidence: 99%

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

2004

View full text Add to dashboard Cite

show abstract

“…taxol). 3,4 It has been shown that pyrrolidine-3-carboxylic acid ( β -proline) is a potent agonist at the strychnine-sensitive glycine receptor, 5 serves as a building block for the preparation of novel inhibitors of bacterial DNA gyrase 6 and forms the central moiety of a conformationally restricted, highly potent fibrinogen receptor antagonist. 7 In addition, β -proline and pyrrolidine-3-acetic acid 8 (homo-β -proline) both can serve as a conformationally restricted γ -amino acid and bind to the γ -aminobutyric acid (GABA) transport system in the brain.…”

mentioning

confidence: 99%

A Practical Ex-Chiral-Pool Synthesis of β-Proline and Homo-β-Proline

Thomas¹,

Orecher²,

Gmeiner³

1998

Synthesis

View full text Add to dashboard Cite

show abstract

“…In Route B, aldehydes 18c, d, 31) e, f 32) and g, 33) which were purchased or prepared according to the literature, were treated with HCl gas and diacetyl monoxime (19) to give oxazole N-oxides 20c-g, followed by treatment with phosphorous oxychloride to afford 4-chloromethyloxazole derivatives (3c-g). 34) In Route C, carboxylic acids 24h 35) and j 32) were prepared according to the literature, and 1,3,4-trimethyl-3-cyclopentenecarboxylate (24i) was synthesized from 1,4-dichloro-2,3-dimethyl-but-2-ene (21). 36) Diethyl malonate was alkylated with 21 and formed a cyclopentene ring 22.…”

Section: Chemistrymentioning

confidence: 99%

“…Carboxylic acids 8A, D and E were purchased, 8G was prepared according to the literature 35) and 3-(5-fluorofuryl)-acrylic acid (8F) was synthesized from ethyl 5-bromofuran-2-carboxylate (27), as shown in Chart 3. Compound 28 was prepared by the Heck reaction from 27 and ethyl ester was hydrolyzed.…”

Section: Chemistrymentioning

confidence: 99%

Novel 2,7-Substituted (<i>S</i>)-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acids: Peroxisome Proliferator-Activated Receptor γ Partial Agonists with Protein–Tyrosine Phosphatase 1B Inhibition

Otake

Azukizawa

Takeda

et al. 2015

CHEMICAL & PHARMACEUTICAL BULLETIN

View full text Add to dashboard Cite

A novel series of 2,7-substituted 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives were synthesized and biologically evaluated. (S)-2-(2-Furylacryloyl)-7-[2-(2-methylindane-2-yl)-5-methyloxazol-4-yl] methoxy-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid tert-butylamine salt (13jE) was identified as a potent human peroxisome proliferator-activated receptor γ (PPARγ)-selective agonist (EC 50 85 nM) and human protein-tyrosine phosphatase 1B (PTP-1B) inhibitor (IC 50 1.0 µM). Compound 13jE partially activated PPARγ, but not PPARα or PPARδ, and antagonized farglitazar, a full PPARγ agonist. C max after the oral administration of 13jE at 10 mg/kg was 28.6 µg/mL (53 µM) in male Sprague-Dawley (SD) rats. Repeated administration of 13jE and rosiglitazone for 14 d at 10 mg/kg/d decreased plasma glucose and triglyceride levels significantly in male KK-A y mice. Rosiglitazone, but not 13jE, significantly increased the plasma volume and liver weight. In conclusion, 13jE showed stronger hypoglycemic and hypolipidemic effects and weaker hemodilution and hepatotoxic effects than rosiglitazone, suggesting that its safer efficacy may be due to its partial PPARγ agonism and PTP-1B inhibition.

show abstract

Asymmetric dipolar cycloaddition reactions: a practical, convergent synthesis of chiral pyrrolidines

Cited by 64 publications

References 29 publications

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

A Practical Ex-Chiral-Pool Synthesis of β-Proline and Homo-β-Proline

Novel 2,7-Substituted (<i>S</i>)-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acids: Peroxisome Proliferator-Activated Receptor γ Partial Agonists with Protein–Tyrosine Phosphatase 1B Inhibition

Contact Info

Product

Resources

About

Asymmetric dipolar cycloaddition reactions: a practical, convergent synthesis of chiral pyrrolidines

Cited by 64 publications

References 29 publications

β2‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides1,2

β2‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides1,2

A Practical Ex-Chiral-Pool Synthesis of β-Proline and Homo-β-Proline

Novel 2,7-Substituted (<i>S</i>)-1,2,3,4-Tetrahydroisoquinoline-3-carboxylic Acids: Peroxisome Proliferator-Activated Receptor γ Partial Agonists with Protein–Tyrosine Phosphatase 1B Inhibition

Contact Info

Product

Resources

About

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2

β²‐amino acids—syntheses, occurrence in natural products, and components of β‐peptides^1,2