Practical Synthesis of a Key Intermediate for Lactacystin from (R)-4-Hydroxymethyl-2-phenyl-4,5-dihydrooxazol-4-ylmethyl Acetate

Miyaoka, Hiroaki; Yamanishi, Makoto; Hoshino, Ayako; Mitome, Hidemichi; Kawashima, Etsuko

doi:10.1248/cpb.56.738

Cited by 7 publications

(1 citation statement)

References 42 publications

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“…The stereoselective construction of the nitrogen‐substituted quaternary carbon atom was the most challenging task amongst all divergent synthetic strategies that were employed of the asymmetric and chiral approaches for the syntheses of lactacystin ( 1 ). Some notable strategies to install the amine‐containing quaternary carbon stereocenter of 1 include an aldol condensation,8c,8i,8k,8x an Overman rearrangement, [8e,8af] Brown's asymmetric crotylation,8o a catalytic Michael addition of a β‐silyl unsaturated imide,8s a Strecker reaction,8u an Ugi reaction,8w a selective addition of trimethylsilyl cyanide to an acyliminium ion,8y and the use of some chiral building blocks 8z. In recent years, Hayes et al [8ab,8ae] reported two syntheses of 1 that use an alkylidene carbene 1,5‐CH insertion and a diastereoselective enolate acylation to construct the chiral amine, whereas Gu and Silverman [8ad] exploited a Dieckmann condensation approach.…”

Section: Introductionmentioning

confidence: 99%

Asymmetric Formal Synthesis of (+)‐Lactacystin

et al. 2014

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A formal synthesis of (+)‐lactacystin was achieved from commercially available isobutyraldehyde and ethyl acrylate. A Baylis–Hillman reaction, an intermolecular nucleophilic displacement under Mitsunobu conditions, a Sharpless asymmetric epoxidation, a palladium(0)‐catalyzed syn‐selective ring opening of an epoxide by treatment with an azide, a one‐pot azide reductive lactamization, and a ruthenium‐catayzed oxidation were employed as the key steps.

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Section: Introductionmentioning

confidence: 99%

Asymmetric Formal Synthesis of (+)‐Lactacystin

et al. 2014

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Neurotrophe Naturstoffe – ihre Chemie und Biologie

Lacoske

Theodorakis

2013

Angewandte Chemie

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Neurodegenerative Erkrankungen und Rückenmarksverletzungen betreffen weltweit etwa 50 Millionen Menschen und verursachen Gesundheitskosten von insgesamt mehr als 600 Milliarden Dollar pro Jahr. Nervenwachstumsfaktoren, d. h. Neurotrophine, sind potenzielle Therapeutika für diese Erkrankungen, denn sie können die Regeneration von Nerven fördern. Durchschnittlich 500 Publikationen jährlich belegen die Bedeutung der Neurotrophine in den biomedizinischen Wissenschaften und ihr Potenzial für therapeutische Anwendungen. Allerdings ist die klinische Verwendung von Neurotrophinen wegen ihres schlechten pharmakokinetischen Profils stark eingeschränkt. Niedermolekulare Verbindungen, die die neurotrophe Aktivität modulieren, bieten hingegen einen vielversprechenden Therapieansatz bei neurologischen Erkrankungen. Die Natur hat für eine beeindruckende Zahl von Naturstoffen mit starken neurotrophen Wirkungen gesorgt. Die aktuellen Strategien zur Synthese dieser Verbindungen sowie deren Fähigkeit, das Wachstum und die Erneuerung von Nervenzellen zu induzieren, bilden den Schwerpunkt dieses Aufsatzes. Es ist davon auszugehen, dass neurotrophe Naturstoffe nicht nur als Leitstrukturen in der Wirkstoffentwicklung genutzt werden können, sondern auch für das nächste große Projekt der Biomedizin: die Kartierung der Hirnaktivität (BAM, Brain Activity Map).

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Neurotrophic Natural Products: Chemistry and Biology

2013

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Neurodegenerative diseases and spinal cord injury affect approximately 50 million people worldwide, bringing the total healthcare cost to over 600 billion dollars per year. Nervous system growth factors, that is, neurotrophins, are a potential solution to these disorders, since they could promote nerve regeneration. An average of 500 publications per year attests to the significance of neurotrophins in biomedical sciences and underlines their potential for therapeutic applications. Nonetheless, the poor pharmacokinetic profile of neurotrophins severely restricts their clinical use. On the other hand, small molecules that modulate neurotrophic activity offer a promising therapeutic approach against neurological disorders. Nature has provided an impressive array of natural products that have potent neurotrophic activities. This Review highlights the current synthetic strategies toward these compounds and summarizes their ability to induce neuronal growth and rehabilitation. It is anticipated that neurotrophic natural products could be used not only as starting points in drug design but also as tools to study the next frontier in biomedical sciences: the brain activity map project.

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Practical Synthesis of a Key Intermediate for Lactacystin from (R)-4-Hydroxymethyl-2-phenyl-4,5-dihydrooxazol-4-ylmethyl Acetate

Cited by 7 publications

References 42 publications

Asymmetric Formal Synthesis of (+)‐Lactacystin

Asymmetric Formal Synthesis of (+)‐Lactacystin

Neurotrophe Naturstoffe – ihre Chemie und Biologie

Neurotrophic Natural Products: Chemistry and Biology

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