Chemistry Reference
In-Depth Information
Kunz and coworkers introduced their chiral carbohydrate based auxiliaries suc-
cessfully onto a solid phase [14]. They synthesized 2,3,4-tri-
O
-pivaloylated-
-d-
galactopyranosyl azide bearing a hydroxyl-functionalized spacer unit at the C6
position of the galactose and immobilized this on a solid phase by using a polymer-
bound chlorosilane. The azide was reduced to the corresponding galactopyrano-
sylamine, which served as a versatile chiral auxiliary in highly diastereoselective
Ugi four-component condensation reactions at ambient temperature. Fluoride-
induced cleavage from the polymeric support furnished N-glycosylated N-acylated
α
β
-amino acid amides
32
(Scheme 1.11).
O
O
1. R
1
CHO (5 eq.)
ZnCl
2
(3 eq.) THF, 20 °C
2. TBAF 3H
2
O (5 eq.),
AcOH (1.7 eq.), THF 20 °C, 48h
O
OH
PivO
PivO
O
Si
O
O
O
O
O
NH
2
OPiv
PivO
PivO
N
OPiv
NH
t
Bu
R
1
+ 5 eq. HCOOH
32
NC
+ 5 eq.
Scheme 1.11
Kunz's auxiliary made available on solid phase and its use in an Ugi reaction.
Pellicciari
et al.
have reported the stereoselective synthesis and preliminary bio-
logical evaluation of (
)-3-methyl-5-carboxythien-2-ylglycine (3-MATIDA),
36
and
37.
They used chiral sugar based auxiliaries
3
and
10
to prepare the enantio-
merically pure unnatural amino acids using a U-4CR [15]. The reaction of thi-
ophene carbaldehyde
33
with
tert
-butyl isocyanide, formic acid, and d-galactosylamine
3
or d-arabinosylamine
10,
respectively, in the presence of zinc chloride in THF at
−
+
)- and (
−
25 °C and subsequent cleavage afforded the
N
-formyl-
N
-galactosyl amino acid
amide
34
in a 17 : 1 diastereomeric ratio and the
N
-formyl-
N
-arabinosyl amino acid
amides
35
in a 32 : 1 diastereomeric ratio, respectively (Scheme 1.12).
Scheme 1.12
Enantioselective preparation of carboxythiophene
α
-amino acids by Ugi reactions.
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