Improved Methodology for the Preparation of Chiral Amines

aminoacid producing the protected amide which can be deprotected under acidic condition.
The second arm of this synthetic strategy starts with the addition of a pair of methyl groups to
the benzylic position of pyruvate through addition of methyl iodide to ketoacid in the
presence of hydroxide. The addition of methylamine and diborane results in the reductive
amination of the carbonyl group, and thus formation of α-aminoacid as a mixture of the two
isomers. Condensation of this moiety with dipeptide formed previously under peptide
forming condition resulted in the formation of amide product which is separated by column
chromatography affording the desired isomer of taltobulin.
t-BOC
N
CHO
N
(C 6 H 5 ) 3 P CO 2 C 2 H 5 t-Boc
CO 2 C 2 H 5 H +
HN CO2 C 2 H 5
O
CO 2 H
CH 3 I
NaOH
O
CO 2 H
CO 2 H
NHCH 3
t-BOC
N
H
CO 2 H
DCC
O
N
H
NHCH 3
O
N
CO 2 R
R
N
H
O
N CO 2 C 2 H 5
Scheme 4.6. Synthesis of Taltobulin
4.1.7. Synthesis of Perzinfote:
Perzinfote is a nonaddictive opiate alternative which is currently used to treat chronic pain. [7]
Preparation starts with the reductive amination of the acetaldehyde derivative with
monocarbobenzyloxy ethylenediamine leading to the disubstituted ethylenediamine (116).
The amine is reacted with the commercially available cyclobutenedione derivative (117)
resulting in the replacement of one of the ethoxy groups in (117) by the free amino group in
(116) to afford the coupled product (118). Transfer hydrogenation of the (118) with 1,4-
cyclohexadiene/Pd leads to the loss of the carbobenzoxy group and the formation of the
transient primary amine (119) which is then cyclised to form eight-membered ring (120).
87