All together: A concise strategy for the first diastereoselective total synthesis of (±)‐schindilactone A is reported. The synthesis features a ring‐closing metathesis, a thiourea/cobalt‐catalyzed Pauson–Khand reaction, and a thiourea/palladium‐catalyzed carbonylative annulation reaction. The chemistry can be applied to the synthesis of structures related to schindilactone A.
Modified cytosines
are important epigenetic marks that exert critical
influences in a variety of cellular processes in living organisms.
However, biological functions of rare modified cytosines, especially
certain functions of 5-formylcytosine (5fC) and 5-carboxylcytosine
(5caC), are still unclear due to the extremely low abundance in biological
samples. In this work, a series of novel hydrazine-based reagents,
which held a hydrazine group as the reaction group, a hydrophobic
triazine group, and two easily charged tertiary amine groups with
different alkyl chains for adjusting the hydrophobicity of the labeling
reagents, were first explored to label rare modified cytosines such
as 5fC and 5caC. The derivatization reaction between 5fC and the labeling
reagents was extremely fast, and more than 99% derivatization efficiency
could be achieved only by vortexing without additional reaction time.
The detection sensitivity of 5fC increased with the increase of the
hydrophobicity of the labeling reagents, the best of which was dramatically
enhanced by 125-fold. The limit of detection was as low as 10 amol,
realizing the most sensitive genome-wide overall quantification for
5fC. Moreover, the labeling reagents were also successfully applied
for the detection of 5caC with 100-fold improvement of sensitivity.
With this method, we achieved the simultaneous detection of 5fC and
5caC in different mammalian tissues using only about 600 ng of genomic
DNA, which was less than one-tenth of the sample consumption for other
reported methods, providing an opportunity to monitor 5fC and 5caC
in precious samples and biology processes that could not be investigated
before.
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