A palladium(II) catalyst,
in the presence of Selectfluor, enables
the efficient and chemoselective transformation of primary amides
into nitriles. The amides can be attached to aromatic rings, heteroaromatic
rings, or aliphatic side chains, and the reactions tolerate steric
bulk and electronic modification. Dehydration of a peptaibol containing
three glutamine groups afforded structure–activity relationships
for each glutamine residue. Thus, this dehydration can act similarly
to an alanine scan for glutamines via synthetic mutation.
The conversion of alkynes to their
corresponding vinyl triflates
in the presence of stoichiometric TMS-triflate was greatly facilitated
by the triflate salt of several transition metal catalysts most especially
Zn(OTf)2. Products are formed in high regioselectivity
under mild conditions. Internal alkynes bearing an aryl substituent
afford vinyl triflates with a modest preference for the Z-isomer especially with larger substituents. A mechanism is put forward
to explain the unique role of silicon in this system.
The dehydration of primary amides to generate their respective nitriles is an isohypsic, or redox neutral, method to install a valuable functional group into a molecule. This process has been known for over 175 years, typically using highly reactive dehydrating agents and high temperatures. Recently, transition metal-catalysis has enabled reactivity under milder reaction conditions, while also tolerating a wide range of functional groups. The removal of water from primary amides is still energetically uphill so a stoichiometric dehydrating agent is required. The dehydrating agents used in recent years can be rather benign, such as acetonitrile to generate acetamide. This Minireview focuses on metalcatalyzed reactions to convert primary amides into nitriles and is organized based on the dehydrating agent.[a] Dr. Figure 1. Bioactive compounds containing a nitrile. Scheme 1. Methods for dehydration of amides. 2 3 4 5 6 7 8
Conditions for the first palladium-catalyzed chemoselective protodecarboxylation of polyenoic acids to give the desired polyenes in good yields are presented. The reactions proceed under mild conditions using either a Pd(0) or Pd(II) catalyst and tolerate a variety of aryl and aliphatic substitutions. Unique aspects of the reaction include the requirement of phosphines, water, and a polyene adjacent to the carboxylic acid.
Phenylcyanocarbene was generated by the reaction of azide with a hypervalent iodonium alkynyl triflate and reacted in situ with 21 different carbocyclic and heterocyclic aromatic compounds. These reactions led to more complex products that frequently underwent subsequent rearrangements. The reactivity was further explored in a mechanistic study to ascertain the chemoselectivity and stereospecificity.
One of the main barriers to explaining the functional
significance
of glycan-based changes in cancer is the natural epitope heterogeneity
found on the surface of cancer cells. To help address this knowledge
gap, we focused on designing synthetic tools to explore the role of
tumor-associated glycans of MUC1 in the formation of metastasis via
association with lectins. In this study, we have synthesized for the
first time a MUC1-derived positional scanning synthetic glycopeptide
combinatorial library (PS-SGCL) that vary in number and location of
cancer-associated Tn antigen using the “tea bag” approach.
The determination of the isokinetic ratios necessary for the equimolar
incorporation of (glyco)amino acids mixtures to resin-bound amino
acid was determined, along with developing an efficient protocol for
on resin deprotection of
O
-acetyl groups. Enzyme-linked
lectin assay was used to screen PS-SGCL against two plant lectins,
Glycine max soybean agglutinin
and
Vicia villosa
. The results revealed a carbohydrate density-dependent affinity
trend and site-specific glycosylation requirements for high affinity
binding to these lectins. Hence, PS-SGCLs provide a platform to systematically
elucidate MUC1-lectin binding specificities, which in the long term
may provide a rational design for novel inhibitors of MUC1–lectin
interactions involved in tumor spread and glycopeptide-based cancer
vaccines.
Here we aimed to explore the feasibility of enhancing the fluorination of organosilanes by appending potassium-chelating groups to the substrates. For this purpose, eight organosilanes were prepared in which a linear or cyclic leaving group, with putative potassium-chelating ability, was attached covalently to a congested silicon atom via an ether linkage to serve as a potential nucleophilic assisting leaving group (NALG). Organosilicon-NALGs with expected strong potassium-chelating capability enhanced reactions with potassium fluoride in acetonitrile to produce organofluorosilanes without any need to separately add phase transfer reagent. Similar rate enhancements were also observed with cyclotron-produced [18F]fluoride ion (t1/2 = 109.7 min, β+ = 97%) in the presence of potassium carbonate in MeCN-0.5% H2O. This study found that metal-chelating NALG units can accelerate fluorination and radiofluorination reactions at sterically crowded silicon atoms.
Griseofulvin is a fungal metabolite and antifungal drug used for the treatment of dermatophytosis in both humans and animals. Recently, griseofulvin and its analogues have attracted renewed attention due to reports of their potential anticancer effects. In this study griseofulvin (1) and related analogues (2–6, with 4 being new to literature) were isolated from Xylaria cubensis. Six fluorinated analogues (7–12) were synthesized, each in a single step using the isolated natural products and Selectflour, so as to examine the effects of fluorine incorporation on the bioactivities of this structural class. The isolated and synthesized compounds were screened for activity against a panel of cancer cell lines (MDA-MB-435, MDA-MB-231, OVCAR3, and Huh7.5.1) and for antifungal activity against Microsporum gypseum. A comparison of the chemical space occupied by the natural and fluorinated analogues was carried out by using principal component analysis, documenting that the isolated and fluorinated analogues occupy complementary regions of chemical space. However, the most active compounds, including two fluorinated derivatives, were centered around the chemical space that was occupied by the parent compound, griseofulvin, suggesting that modifications must preserve certain attributes of griseofulvin to conserve its activity.
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