Biomedical Engineering Reference
In-Depth Information
The divergent strategy, which was pioneered by Newkome and Tomalia
(
vide infra
), is that dendrimers are built from the central core going outward
to the periphery. A number of reactive groups,
n
, on the dendrimer periphery
react with
n
monomer units to add a new generation to the dendrimer in each
repeat cycle. This creates 2
n
or 3
n
reactive sites in the succeeding repeat cycles
depending on whether the monomer unit's branch multiplicity is 2 or 3 (i.e.,
AB2 vs AB3 monomer).
204
In this manner, the number of coupling reactions
increases with each successive generation.
205,208-210
In the convergent strategy,
211-213
the dendrimer is built from the periphery
toward the central core.
204
The initial reaction sites are on the periphery of the
dendrimer, while the reactions take place at the reactive core (called the
focal
point
).
204
The number of coupling reactions to add each new generation is usu-
ally 2 or 3, depending on branch multiplicity during the synthesis that makes
defective products easier to separate. Thus, the dendrimers resulting from the
convergent strategy are generally more homogeneous and often monodisperse
unlike those prepared by a divergent approach, where defects begin to accu-
mulate at higher generation numbers when a large number of coupling or con-
densation reactions have to occur on a congested dendrimer surface. Therefore,
dendrimers prepared by the divergent approach are usually monomolecular
species but contain significant defects while those prepared by the convergent
strategy are limited to lower generation numbers.
204
The group of Sato reported the synthesis of dendritic chiral catalysts, which
have rigid hydrocarbon backbones with no heteroatoms.
214
They also showed
uses as chiral catalysts in the enantioselective addition of dialkylzincs to alde-
hydes (Figure 1 of Sato's paper). The chiral dendrimers were synthesized using
the following protocol.
2.5.1 Protocol for Synthesis Dendrimers
214
(1)
Use the Hagihara-Sonogashira coupling reaction
215
between ethyl 4-iodo-
benzoate (
2
) and ethynyltrimethylsilane followed by subsequent reduction
of the ester and removal of a trimethylsilyl group that leads to the formation
of the intermediate product 4-ethynylbenzyl alcohol
3
(
Scheme 2.1
).
(2)
Methylation of
3
and treatment with (1
R
,2
S
)-ephedrine and potassium car-
bonate produces the chiral amino alcohol labeled
4.
(3)
Following
Scheme 2.2
, when 1,3,5-triiodobenzene (
5
) was treated with two
molar equivalents of
4
, a biscoupled product
6
was obtained as a major
product.
(4)
When compound
5
was treated with excess
4
,
1a
(G1) with three ephedrine
moieties was synthesized at 66% yield.
(5)
Compound
6
was further converted to a terminal alkyne
7
by coupling
with ethynyltrimethylsilane and subsequent removal of the trimethylsilyl
group.
