738 research outputs found
Scalable De Novo Synthesis of Aldgarose and Total Synthesis of Aldgamycin N
Since the accompanying study had shown that the introduction of the eponymous aldgarose sugar to the C5âOH group of the macrocyclic aglycone of aldgamycin N is most difficult, if not even impossible, the synthesis route was revised and the glycosidation performed at an earlier stage. To mitigate the âcostâ of this strategic amendment, a practical and scalable de novo synthesis of this branched octose was developed. The glycoside formation required mild conditions; it commenced with the reaction of the aglycone with the trichloroacetimidate donor to give a transient orthoester, which slowly rearranged to the desired aldgaropyranoside. The presence of the polar peripheral groups in the product did not impede the selective lateâstage functionalization of the macrolide ring itself: the contained propargylic alcohol entity was readily transformed into the characteristic acyloin motif of the target by a rutheniumâcatalyzed transâhydrostannation followed by a modified ChanâLamâtype coupling
Total Synthesis of Mycinamicin IV as Integral Part of a Collective Approach to Macrolide Antibiotics
The total synthesis of the 16-membered macrolide mycinamicin IV is outlined, which complements our previously disclosed, largely catalysis-based route to the aglycone. This work must also be seen in the context of our recent conquest of aldgamycin N, a related antibiotic featuring a similar core but a distinctly different functionalization pattern. Taken together, these projects prove that the underlying blueprint is integrative and hence qualifies for a collective approach to this prominent class of natural products. In both cases, the final glycosylation phase mandated close attention and was accomplished only after robust de novo syntheses of the (di)deoxy sugars of the desosamine, chalcose, mycinose and aldgarose types had been established. Systematic screening of the glycosidation promoter was also critically important for success
On a sequential linear programming approach to finding the smallest circumscribed, largest inscribed, and minimum zone circle or sphere
Sequential linear programming methods have been successfully
used to solve some sphere and circle problems. Indeed, empirical evidence shows that these frequently find the required solutions in one step. An analysis is presented here which attempts to give an explanation of this phenomemon
One-step behaviour of a method for finding a maximal solution of a system of linear inequalities
It has been observed empirically that a simple linearization method applied to the problem of finding maximal solutions to systems of linear inequalities frequently terminates in one step.
This is normally a Kuhn-Tucker point, and depending on the starting point, can be a global solution.
An explanation of this phenomenon is given, and this is illustrated by examples
Total Synthesis of the Tetracyclic Pyridinium Alkaloid epi-Tetradehydrohalicyclamine B
The first total synthesis of a tetracyclic marine pyridinium alkaloid hinged on recent advances in chemoselectivity management: While many classical methods failed to afford the perceptively simple pyridine-containing core of the target, nickel/iridium photoredox dual catalysis allowed the critical CâC-bond to be formed in good yield. Likewise, ring closing alkyne metathesis (RCAM) worked well in the presence of the unhindered pyridine despite the innately Lewis acidic Mo(+6) center of the alkylidyne catalyst. Finally, an iridium catalyzed hydrosilylation was uniquely effective in reducing a tertiary amide without compromising an adjacent pyridine and the lateral double bonds; this transformation is largely without precedent. The second strained macrocycle enveloping the core was closed by intramolecular N-alkylation with formation of the pyridinium unit; the reaction proceeded site- and chemoselectively in the presence of an a priori more basic tertiary amine
Monitoring der Baby Freundlichen SpitÀler in zertifizierten Geburtskliniken (Baby Friendly Hospital Initiative): Bericht 2017: eine Analyse im Auftrag der UNICEF Schweiz
Total Synthesis of Mycinolide IV and PathâScouting for Aldgamycin N
Proofâofâconcept is provided that a large estate of 16âmembered macrolide antibiotics can be reached by a âunifiedâ approach. The key building block was formed on scale by an asymmetric vinylogous Mukaiyama aldol reaction; its alkene terminus was then converted either into the corresponding methyl ketone by Wacker oxidation or into a chainâextended aldehyde by catalystâcontrolled branchâselective asymmetric hydroformylation. These transformations ultimately opened access to two structurally distinct series of macrolide targets. Notable lateâstage maneuvers comprise a rare example of a rutheniumâcatalyzed redox isomerization of an 1,3âenyneâ5âol into a 1,3âdieneâ5âone derivative, as well as the elaboration of a tertiary propargylic alcohol into an acyloin by transâhydrostannation/ChanâLamâtype coupling. Moreover, this case study illustrates the underutilized possibility of forging complex macrolactone rings by transesterification under essentially neutral conditions
Production and characterization of anti-human interferon Îł receptor antibody fragments that inhibit cytokine binding to the receptor
Three single-chain antibody fragments that recognize the extracellular human interferon γ receptor α-chain (IFNγR), and inhibit the binding of human IFNγ, have been produced in Escherichia coli. These fragments are derived from murine anti-receptor monoclonal antibodies, and comprise the variable heavy (VH) domain linked to the variable light (VL) chain through a 15 amino acid linker [(GGGGS)3]. Using surface plasmon resonance technology (BIAcore), the soluble proteins were shown to retain a high affinity for recombinant IFNγR, and by radioimmunoassay to possess high inhibitory activity towards IFNγ-binding to human Raji cells. The antibody fragments most likely recognize epitopes that overlap the cytokine binding site on the receptor surface. Attempts to dissect further the antibodies to isolated VH- and VL-chains and to synthetic linear and cyclic peptides derived from the individual complementarity determining regions failed to afford fragments with significant IFNγR binding affinity. Nevertheless, these native-like variable region fragments and petidomimetics derived from them are of interest in the design of novel IFNγR antagonist
Aktion HerzCheckŸ in Apotheken : im Rahmen des Projektes Frau&Herz TabakprÀvention 2014-2017 : Evaluation HerzCheckŸ in Apotheken, Telefonische Nachbefragung 2018
- âŠ