Total Synthesis of Proteasome Inhibitor (-)-Omuralide through Asymmetric Ketene [2 + 2]-Cycloaddition

Organic Letters
Pauline RullièreJean-François Poisson

Abstract

The total synthesis of (-)-omuralide, a potent specific proteasome inhibitor, has been achieved through an unprecedented route. The C3 and C4 chiral centers of the natural product have been selectively installed by an asymmetric [2 + 2]-cycloaddition between an unusual oxadisilinane ketene and a chiral enol ether, while the γ-lactam core was prepared by a single-pot two-step Beckmann transposition. The C5 quaternary center was eventually defined by an original selective oxidative desymmetrization of a spiro cyclic oxadisilinane thanks to the anchimeric assistance of a proximal hydroxyl group.

References

Oct 28, 1998·Trends in Cell Biology·D H Lee, A L Goldberg
Nov 18, 2000·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·H Tomoda, S Omura
Oct 23, 2004·The Journal of Organic Chemistry·Hidenori OoiSusumi Hatakeyama
Jan 5, 2006·Organic & Biomolecular Chemistry·Christopher J HayesMatthew D Selby
Jan 28, 2006·The Journal of Organic Chemistry·Nobuhisa FukudaMasakatsu Shibasaki
Oct 6, 2006·Organic Letters·Julien CecconJean-François Poisson
Apr 19, 2007·Chemistry, an Asian Journal·Masakatsu ShibasakiNobuhisa Fukuda
Feb 22, 2008·The Journal of Organic Chemistry·Christopher J HayesJeremy C Prodger
Mar 6, 2008·The Journal of Organic Chemistry·Masaharu HashimotoYasutaka Ishii
Jul 3, 2008·Journal of the American Chemical Society·Yuya A LinBenjamin G Davis
Sep 19, 2008·Organic Letters·Benjamin DarsesJean-François Poisson
Sep 16, 2011·The Journal of Organic Chemistry·Wenxin Gu, Richard B Silverman
Jan 26, 2016·Accounts of Chemical Research·Jean-Pierre DeprésAndrew E Greene
Jul 3, 1998·Angewandte Chemie·E J CoreyTohru Nagamitsu

❮ Previous
Next ❯

Citations


❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

Biochemical Society Transactions
S K Law, A W Dodds
Clinical Anatomy : Official Journal of the American Association of Clinical Anatomists & the British Association of Clinical Anatomists
Richard J Pusey
© 2022 Meta ULC. All rights reserved