A convergent and stereoselective synthesis of the C1-C14 stretch of (+)-discodermolide demonstrates the utility of the "asymmetric catalysis approach" to complex polypropionates. The preparation of this complex synthon requires 15 steps in the longest linear sequence and 19 steps total from inexpensive materials.
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http://dx.doi.org/10.1021/ol7029933 | DOI Listing |
Nat Commun
July 2024
Department of Bioengineering, School of Engineering and Applied Sciences, University of Pennsylvania, Philadelphia, PA, USA.
Recently, targeted degradation has emerged as a powerful therapeutic modality. Relying on "event-driven" pharmacology, proteolysis targeting chimeras (PROTACs) can degrade targets and are superior to conventional inhibitors against undruggable proteins. Unfortunately, PROTAC discovery is limited by warhead scarcity and laborious optimization campaigns.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
January 2021
Department of Physiology, University of Auckland, Auckland, New Zealand.
One of the major roles of the intracardiac nervous system (ICNS) is to act as the final site of signal integration for efferent information destined for the myocardium to enable local control of heart rate and rhythm. Multiple subtypes of neurons exist in the ICNS where they are organized into clusters termed ganglionated plexi (GP). The majority of cells in the ICNS are actually glial cells; however, despite this, ICNS glial cells have received little attention to date.
View Article and Find Full Text PDFJ Org Chem
April 2019
Integrated Chemistry Engine , Eisai AiM Institute, 4 Corporate Drive , Andover , Massachusetts 01810 , United States.
Syntheses of a crystalline polycyclic halichondrin C1-C14 building block starting from a d-gulono-1,4-lactone-derived intermediate in the current Halaven manufacturing process are described. Key features of the syntheses include an acid-catalyzed tandem intermolecular oxy-Michael/intramolecular trans-ketalization reaction and stereoselective Kishi reductions.
View Article and Find Full Text PDFAm J Physiol Cell Physiol
July 2016
Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York
The process of entering the bloodstream, intravasation, is a necessary step in the development of distant metastases. The focus of this review is on the pathways and molecules that have been identified as being important based on current in vitro and in vivo assays for intravasation. Properties of the vasculature which are important for intravasation include microvessel density and also diameter of the vasculature, with increased intravasation correlating with increased vessel diameter in some tumors.
View Article and Find Full Text PDFOrg Biomol Chem
May 2014
Division of Natural Products Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India.
A flexible stereoselective approach to the common C1-C14 skeleton present in natural products of the pseudomonic acid family is described. The strategy has been extended and the total synthesis of pseudomonic acid methyl monate C was achieved. The key synthetic reactions utilized include Achmatowicz rearrangement, Johnson-Claisen rearrangement, Julia-Kocienski olefination, and Horner-Wadsworth-Emmons olefination reaction.
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