Chemistry Reference
In-Depth Information
Typical procedure. N-Carboxy-
l
-valine anhydride [894]:
To a solution of N-Boc-l-
valine (500 mg, 2.3 mmol) and triphosgene (273 mg, 0.92 mmol) in anhydrous
ethyl acetate (55 mL), distilled triethylamine (353 mL, 2.5 mmol) was added over a
period of 30 s at room temperature; Et
3
N
HCl precipitated immediately. The vessel
was connected to a manometer in order to monitor CO
2
evolution while main-
taining vigorous stirring of the reaction mixture. The requisite amount of CO
2
was
generated in 3 h, whereupon the suspension was filtered. The solid Et
3
N
HCl was
washed with a small portion of ethyl acetate (10 mL), and the filtrate was concen-
trated to dryness. The residue obtained was crystallized from dichloromethane and
petroleum ether at
20
C to give the title compound as white crystals (330 mg,
75%).
Poly(g-stearyl l-glutamate) was prepared by polymerization of the corresponding
amino acid N-carboxyanhydride monomer 1214 [895]. The cyclic N-carboxyanhy-
dride monomer 1214 was synthesized using triphosgene.
O
O
(CCl
3
O)
2
CO
(CH
2
)
12
O
OH
THF, 50°C, 1h
NH
2
1213
O
O
(CH
2
)
12
O
O
H
N
O
1214
Typical procedure. g-Stearyl a,
l
-glutamate N-carboxyanhydride 1214 [895]:
g-Stearyl
a,l-glutamate 1213 (10 g, 0.0251 mol) was suspended in THF (150 mL), and the
reaction flask was fitted with a condenser which was vented into concentrated am-
monium hydroxide solution to trap HCl or phosgene gas. After warming to 50
C,
triphosgene (2.52 g, 0.0085 mol; 0.33 equiv.) was added as a single aliquot. The
slurry obtained usually became homogeneous within 1 h. After about 1 h, the re-
action mixture was concentrated to about one-third to a half of its original volume
in vacuo and poured into twice its volume of hexane. After overnight refrigeration,
the crystals were recovered by suction filtration and then redissolved in chloroform
or dichloromethane. After shaking with a small amount of sodium carbonate, this
solution was filtered through a cake of Celite. The filtrate was concentrated, poured
into hexane, and refrigerated. The recrystallization step was repeated twice. The
yield was typically 85-90%.
d,l-Trifluoroalanine N-carboxy anhydride (d,l-TFANCA) 1217, a reactive inter-
mediate for the synthesis of low surface energy polypeptides, has been synthesized
by phosgenation of 3,3,3-d,l-trifluoroalanine in THF [896]. Solid triphosgene was
used as the phosgene source and the procedure of Daly and Poch´ [893] for natural
