Biomedical Engineering Reference
In-Depth Information
Fluorous-tagged
linker
Capping
building block
RuL
n
O
Propagating
building block
Ns
Ns
O
1. Ru-cat., CH
2
Cl
2
, 45°C
2. HF
·
Py
Initiation
N
N
O
O
Si
i-
Pr
2
OH
OH
R
F
Termination
Propagation
112
117
O
O
Ns
1. Ru-cat., CH
2
Cl
2
, 45°C
2. HF
·
Py
O
N
O
Si
i-
Pr
2
OH
N
HO
Ns
R
F
113
118
OTBS
1. Ru-cat., CH
2
Cl
2
, 45°C
2. HF
·
Py
O
O
O
O
Si
i-
Pr
2
OH
OH
HO
R
F
114
119
O
Ns
Ns
N
O
Ru-cat., CH
2
Cl
2
, 45°C
N
O
O
115
120
R
F
1. Ru-cat., CH
2
Cl
2
, 45°C
2. HF
·
Py
OH
N
OH
Ns
Ns
121
O
N
O
Si
i-
Pr
2
116
R
F
Ns
1. Ru-cat., CH
2
Cl
2
, 45°C
2. HF
·
Py
N
HO
OH
122
SCHEME 15.10
remained coupled to the tag. The chirality was initially introduced in the building
phase of propagating and capping building blocks, giving rise to an impressive array
of stereochemically diverse oligomeric skeletons. It is worth noting that the final
structures obtained were controlled by the nature of the oligomeric sequences that
dictated the outcome of the pairing metathesis cascades. In most cases, the propa-
gating building block participated in the cascade. For example, compounds
112
114
-
117
119
were converted into
, respectively, which contain two cycles. The cyclo-
pentene and cycloheptene moieties were directly involved in mediating the propa-
gation. In other cases, the propagating building block was ignored by the cyclization
event, favoring a direct scaffold reprogramming that involved linker and capping
building blocks only. For example, the cycloheptene moiety of
-
did not participate
in the cyclization cascade, leading instead to the bridged macrocycle
115
. In other
examples, a competition between two different metathesis pathways was observed,
leading tomultiple final products. For example, substrate
120
entered two competitive
cyclization modes that led to 7- and 13-membered silaketal rings, which after
desilylation afforded structurally distinct small molecules
116
. The choice
of building blocks and the strategic order in which they were assembled were critical
to the success of the strategy defined by a versatile and modular pairing process. The
ethos of DOS was preserved by the use of a short five-step synthetic sequence
121
and
122
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