Electrophilic halofunctionalization
reactions have undergone a
resurgence sparked by recent discoveries in the field of catalytic
asymmetric halocyclizations. To build mechanistic understanding of
these asymmetric transformations, a toolbox of analytical methods
has been deployed, addressing the roles of catalyst, electrophile
(halenium donor), and nucleophile in determining rates and stereopreferences.
The test reaction, (DHQD)2PHAL-catalyzed chlorocyclization
of 4-arylpent-4-enoic acid with 1,3-dichloro-5,5-dimethylhydantoin
(DCDMH), is revealed to be first order in catalyst and chlorenium
ion donor and zero order in alkenoic acid substrate under synthetically
relevant conditions. The simplest interpretation is that rapid substrate–catalyst
binding precedes rate-limiting chlorenium attack, controlling the
face selectivity of both chlorine attack and lactone closure. ROESY
and DFT studies, aided by crystal structures of carboxylic acids bound
by the catalyst, point to a plausible resting state of the catalyst–substrate
complex predisposed for asymmetric chlorolactonization. As revealed
by our earlier labeling studies, these findings suggest modes of binding
in the (DHQD)2PHAL chiral pocket that explain the system’s
remarkable control over rate- and enantioselection-determining events.
Though a comprehensive modeling analysis is beyond the scope of the
present work, quantum chemical analysis of the fragments’ interactions
and candidate reaction paths point to a one-step concerted process,
with the nucleophile playing a critical role in activating the olefin
for concomitant electrophilic attack.
Hydrogen peroxide (H2O2) plays a key role in environmental chemistry, biology, and medicine. H2O2 concentrations typically are 6 to 10 orders of magnitude lower than that of water, making its quantitative detection challenging. We demonstrate that optimized NMR spectroscopy allows direct, interference-free, quantitative measurements of H2O2 down to submicromolar levels in a wide range of fluids, ranging from exhaled breath and air condensate to rain, blood, urine, and saliva. NMR measurements confirm the previously reported spontaneous generation of H2O2 in microdroplets that form when condensing water vapor on a hydrophobic surface, which can interfere with atmospheric H2O2 measurements. Its antimicrobial activity and strong seasonal variation speculatively could be linked to the seasonality of respiratory viral diseases.
Ganglioside GD2 is an attractive tumor-associated carbohydrate antigen for anti-cancer vaccine development. However,i ts lowi mmunogenicity and the significant side effects observed with anti-GD2 antibodies present significant obstacles for vaccines.T oo vercome these,anew GD2 derivative bearing an N-acetamide (NHAc) at its non-reducing end neuraminic acid (9NHAc-GD2) has been designed to mimic the 9-O-acetylated-GD2 (9OAc-GD2), aG D2 based antigen with ar estricted expression on tumor cells.9 NHAc-GD2 was synthesized efficiently via achemoenzymatic method and subsequently conjugated with ap owerfulc arrier bacteriophage Qb.M ouse immunization with the Qb-9NHAc-GD2 conjugate elicited strong and long-lasting IgG antibodies, which were highly selective toward9 NHAc-GD2 with little cross-recognition of GD2. Immunization of canines with Qb-9NHAc-GD2 showed the construct was immunogenic in canines with little adverse effects,p aving the wayf or future clinical translation to humans.
Electrophilic bromination of pyrroles bearing carbonyl substituents at C-2 typically results in a mixture of the 4- and 5-brominated species, generally favoring the 4-position. Herein, we describe a substrate-controlled regioselective bromination in which tetra-butyl ammonium tribromide (TBABr) reacts with pyrrole-2-carboxamide substrates to yield the 5-brominated species as the predominant (up to >10:1) product.
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