Biomedical Engineering Reference
In-Depth Information
15.4.4.1. Folding Pathway: Control by the Substrate
Cells assemble amino
acids in a sequence that encodes for the folding of the protein, defining its final three-
dimensional structure and function. The biosynthesis is usually followed by further
posttranslational modifications that ultimatelymodulate the biological function of the
protein. Similarly, small organic building blocks can be coupled in a programmed
manner, the order and nature of building blocks encoding for the chemical
transformation that will dictate the structure of the resulting molecular skeleton
and its associated putative function within a cellular context. The molecular scaffold
arising from a chemical transformation can undergo another round of chemical
modifications to provide small molecules with additional biological properties.
Spiegel et al. strategically used a Fukuyama-Mitsunobu protocol to assemble
alkenes
and produce 11 structurally distinct polyunsaturated
oligomers in moderate to excellent yield (Scheme 15.5) [33]. Products
24
and alkynes
25
were
independently subjected to ruthenium-catalyzed ene-ene, ene-yne, ene-yne-ene,
26
-
32
NHR
H
H
RO
RO
RO
NHR
NHR
(
R
)-
24
25
(
S
)-
24
R = H, Boc, Bz, Bs
PPh
3
, DEAD, THF
0°C to rt
H
H
RO
NHR
H
RO
R
N
H
RO
N
R
R
NHR
NHR
(
S
,
S
)-
26
(72%)
(
R
,
R
)-
26
(79%)
(
S
,
R
)-
27
(56%)
(
R
,
S
)-
27
(68%)
(
S
)-
28
(
85%)
(
R
)-
28
(82%)
(
S
)-
29
(99%)
(
R
)-
29
(98%)
NHR
H
H
RO
N
N
R
RO
R
N
R
H
NHR
(
S
,
S
)-
30
(72% over two steps)
(
S
,
R
)-
31
(92% over two steps)
(
rac
)-
32
(86% over two steps from (
rac
)-
24
)
PCy
3
Ru
Cy
3
P
Cl
Cl
Grubbs' cat. (5 mol%)
PhH, ethylene, reflux
Ph
NR
RN
RO
NHR
H
H
H
RO
H
NHR
RN
R
NHR
(
S
,
S
)-
37
(74% from
30
)
(
S
,
R
)-
38
(57% from
31
)
RO
(
S
)-
35
(
82% from
28
)
(
R
)-
35
(87% from
28
)
H
NR
RN
(
S
,
S
)-
33
(75% from
26
)
(
R
,
R
)-
33
(77% from
26
)
(
S
,
R
)-
34
(79% from
27
)
(
R
,
S
)-
34
(85% from
27
)
NHR
RN
H
H
RO
H
NHR
RO
(
S
)-
36
(
58% from
29
)
(
R
)-
36
(
56% from
29
)
(
rac
)-
39
(56% from
32
)
Me
N
CH
2
Cl
2
0°C to rt
O
O
N
N
O
Me
NR
O
OR
RN
N
H
N
N
NHR
N
O
R
O
H
H
RO
Me
N
N
N
N
H
NN
NHR
N
NR
N
H
O
O
O
RHN
Me
H
NR
N
N
RO
O
HN
H
H
Me
R
R
RO
(
S
,
S
,
R
,
R
)-
42
(90% from
37
)
(dr >15:1)
(
S
,
S
,
R
,
S
)-
43
(93% from
38
)
(dr > 20:1)
40
(97% from
35
)
(dr = 1:1)
41
(94% from
36
)
(dr > 20:1)
44
(46% from
39
)
(dr > 20:1)
SCHEME 15.5
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