Biomedical Engineering Reference
In-Depth Information
FIGURE 11.15 Characterization of a new alkyne-alkene macrocyclization reaction. (a) In
DNA-templated format, the reaction was performed incubating the reagents with 500 mM
Na 2 PdCl 4 at 37 Cfor1horat25 C for 20 min. The reaction was analyzed by PAGE and
MALDI-TOF mass spectrometric analysis. (b) In non-DNA-templated format, the macrocyclic
enone product was characterized by 1 H NMR, 13 C NMR, COSY, UV-visible spectrometry,
and high-resolution mass electrospray. The product formation probably proceeds through the
following steps: formation of Pd(II)-alkynyl intermediate; insertion of the alkene into the Pd-
alkyne bond; -hydride elimination to form a conjugated enyne; Pd(II)-mediated hydration of
the alkyne to form an enol
-allyl Pd complex; tautomerization and
-allyl Pd protonation to
generate the trans enone.
Macrocyclic compounds represent a niche class of chemical scaffolds. Typically,
they are constituted by 12 or more ring atoms and display several appendages around
the cyclic structures [82] (Figure 11.16). Despite the relatively high molecular weight
(500 to 2000 Da), such compounds are often capable of establishing very effec-
tive surface interactions with their target protein, modulating its biological function
[82-85]. Additionally, several naturally occurring substances, which have been so
far demonstrated to have highly relevant biological properties, often exhibit cyclic
conformations very similar to synthetic macrocycles [82-85].
Macrocyclic compounds with sufficiently diverse structures and substituents are
not easily accessible through traditional organic synthesis. Indeed, most of the
preparations of large ring-compounds are plagued by slow rates of intramolecular
FIGURE 11.16 General structure of an ensemblins library compound. According to this
structure, Ensemble has generated various libraries, each containing up to 6
×
10 4
members.
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