Chemistry Reference
In-Depth Information
OMe
NCS
Me
N
N
N
HO
n
-C
6
H
13
O
N
NHMe
410
O
HO
HO
O
409
P
O
O
411
OH
O
O
OR
O
N
O
H
O
N
408
NMe
3
H
O
413
412
O
Me
NH
Me
N
N
O
N
N
N
Cl
N
Me
F
N
N
Cl
H
O
F
3
C
414
415
416
FIGURE 10.6.
Compounds of pharmaceutical and synthetic interest potentially accessible
from 1-azaspirane skeleton
408
.
restricted nitrogen-bearing ring systems display an extensive range of important
biological activities and are of great interest to the pharmaceutical industry.
154
For
example,
, a GABAa agonist, has the potential for treatment of anxiety and
seizure disorders,
155
azaspiro[4.5]decanyl amide
414
415
and its analogs are potent
-receptor and display analgesic activity,
156
and selective binders to the opioid
m
-receptor agonist (Figure 10.6).
157
Second,
as will be outlined in the ensuing discussion, 1-azaspiro[4.5]decane and -[5.5]
undecane systems also form the substructure of a diverse range of natural products
409
while compound
416
is an antipruritic
k
which, almost without exception, are imbued with biological activity.
158
Notwithstanding the evident potential value of nitrenium ion azaspirocyclization
as a method to access biologically active natural product and pharmaceutical agents,
Kikugawa and Glover's methodology lay unutilized for more than a decade before
being employed by Wardrop and Basak in their asymmetric synthesis of
(
-
411
) (Scheme 10.67).
159
Isolated from
Penicillium thomii
RA-
89 by Takeda Industries, this alkaloid is a potent muscarinic M
1
receptor antagonist
and as
)-TAN1251A (
411
such has
therapeutic potential
for gastrointestinal and respiratory
