thioesters yielding a small library of 7-, 8- and 10-membered
cyclopeptides, which could not be prepared efficiently using the
previously reported methods. A model of reactivity based on
ring size and sequence was drawn by using computational
chemistry. The conformational behavior of cyclodipeptides was
studied by X-ray on the homodiketopiperazine series. The con-
formers obtained by empirical force-field calculations showed
high levels of similarity with the X-ray results. Empirical force-
field calculations were also used to predict the conformational
behavior of diazocanes. Homodiketopiperazines have showed
envelope-like conformational preferences, while diazocanes
prefer chair-like conformations. Work is currently in progress to
expand this Staudinger-mediated cyclization approach to the
synthesis of other medium-sized cyclopeptides.
Scheme 2 Solution phase synthesis of
tripeptide.
a 10-membered cyclic
Notes and references
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In summary, we have developed a new, straightforward and
powerful strategy towards small cyclic di- and tripeptides that
relies on a Staudinger-mediated ring closure. This was demon-
strated by the successful ring-closure of a series of azido peptide
This journal is © The Royal Society of Chemistry 2012
Org. Biomol. Chem., 2012, 10, 8055–8058 | 8057