From Natural to Rationally Designed Artificial Enediynes: Towards New Anticancer Antibiotics Activable at Will - Polyynes: Synthesis, Properties, and Applications - page 462

by a double bond and an epoxide as safety catch. However, as described in
the following paragraphs, different safety catches have also been proposed.

19.4.1 C OMPOUNDS WITH A D OUBLE B OND AS A S AFETY C ATCH

This family of compounds, constituted mainly by a series of [7.3.1] deri-
vatives, 86 but including also [7.4.1], [8.3.1] and [9.3.1] polycyclic compounds,
is characterized by the fact that the same synthetic strategy was followed for
their preparation. That is, the formation of the cyclic enediyne system was
achieved by the attack of the acyclic enediyne onto an aldehyde by one of
the methods described above and illustrated in Scheme 19.17 for the for-
mation of [7.3.1] systems.

SCHEME 19.17

Apart from R 1 , which can be either a hydrogen or an alcohol protecting
group, the difference in the [7.3.1] analogs lies only in the nature of the
substituents in the 6-membered ring. For derivative 67, the triggering event
is the reduction of the C

C double bond to give a 1,4-diketone, which
shows interesting DNA cleavage activity that has been enhanced when the
incubation was performed in the presence of NaBH 4 , as a result of the
additional reduction of the two carbonyl groups (Scheme 19.18). 86

¼

SCHEME 19.18