A chemo- and diastereoselective iron-catalyzed cross-coupling between C-bromo mannopyranoside derivatives and 2-methyl-1-propenylmagnesium bromide was developed. This method was used as the key step ...for the synthesis of the mirror image of the C31–C40 and C43–C52 fragments of amphidinol 3 (AM3). These syntheses were achieved from a common trans-tetrahydropyran derived from d-mannose.
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Novel oxotriazinoindoles (
OTI
s) were recently reported as highly efficient and selective aldose reductase inhibitors. Here, a series of novel
N(2)
-substituted oxotriazinoindoles was developed with ...the aim to investigate molecular interactions within the aldose reductase (ALR2) inhibitor binding site. About twice increased inhibition efficacy of the most efficient derivative
14
(
N(2)
-CH
2
CH
2
COOH) compared to the unsubstituted lead
OTI
was obtained, yet at the expense of selectivity relative to anti-target aldehyde reductase (ALR1). To explain the major drop in selectivity, observed also in other
N(2)
-substituted derivatives, in silico molecular modeling approach revealed the role of extra interactions with the residues of Arg309, Arg312 and Met302 located in the additional
C
-terminal loop of ALR1 missing in ALR2, which can prevent or enhance binding in ALR1. These key findings will be used for development of the next generation of selective OTI inhibitors.
After a brief account of the biological properties of pamamycins, this review highlights the latest developments on the total synthesis and the biosynthesis of these macrodiolides.
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A convenient and high yielding method for the cleavage and scavenging of p-methoxybenzyl protecting group of several alcohols using tert-butyl bromide in refluxing acetonitrile is ...described. Under these mild conditions other protecting groups such as acid sensitive allyl, benzyl, and Me3CPh2Si ethers, or isopropylidene acetals were unchanged. Interestingly, a selective alkoxy-PMB cleavage was observed in the presence of a PMB phenoxy ether.
Covering: 1991 to the end of 2013
This review highlights the isolation and the structural determination of amphidinol 3 (AM3), as well as the synthetic efforts to its preparation. The mechanism of ...action of AM3 will not be developed herein.
This review highlights the isolation and the structural determination of amphidinol 3 (AM3) with an emphasis on the different synthetic approaches.
The diastereoselective synthesis of the C17-C30 fragment of amphidinol 3 (AM3) 1 was achieved from the enantio-enriched aldehyde 20, Weinreb amide 14 and 2-bromo-3-(trimethylsilyl)propene, which was ...used as a bifunctional conjunctive reagent. The absolute configuration of the stereogenic centers, in both aldehyde 20 and Weinreb amide 14, were efficiently controlled by using (+)-(R)-methyl-p-tolylsulfoxide as the unique source of chirality.
The cell division cycle 25 phosphatases (CDC25A, B, and C; E.C. 3.1.3.48) are key regulator of the cell cycle in human cells. Their aberrant expression has been associated with the insurgence and ...development of various types of cancer, and with a poor clinical prognosis. Therefore, CDC25 phosphatases are a valuable target for the development of small molecule inhibitors of therapeutic relevance. Here, we used an integrated strategy mixing organic chemistry with biological investigation and molecular modeling to study novel quinonoid derivatives as CDC25 inhibitors. The most promising molecules proved to inhibit CDC25 isoforms at single digit micromolar concentration, becoming valuable tools in chemical biology investigations and profitable leads for further optimization.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
A practical access to four new halogen-substituted pyrrole building blocks was realized in two to five synthetic steps from commercially available starting materials. The target compounds were ...prepared on a 50 mg to 1 g scale, and their conversion to nanomolar inhibitors of bacterial DNA gyrase B was demonstrated for three of the prepared building blocks to showcase the usefulness of such chemical motifs in medicinal chemistry.
The Diels-Alder reaction of quinones is both of historical and current importance, and numerous asymmetric and catalytic versions have been described. Herein we describe the dramatic rate enhancement ...observed in the Diels-Alder reactions of a large variety of quinones with moderately activated dienes when hexafluoroisopropanol is used as a solvent, even allowing reactions that are not observed in dichloromethane. When chiral sulfinylquinones are used, hexafluoroisopropanol has a marked effect on stereoselectivity. Since the Diels-Alder reactions of sulfinylquinones are known to be an entry into several classes of natural products, and many other quinone cycloadditions have found widespread use in synthesis, the findings described herein will further facilitate their application.
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