462
Basiuk, Gromovoy:
trometer (Nauchpribor, Orel, Russia); DOP samples were in the form of suspensions in glycerol. En-
ergy of bombarding argon atoms was 3.5 keV; intensity of bombarding beam, about 1 µA; angle of
incidence to the target, 70° to the normal.
Dipeptides H-Gly-Gly-OH, H-Gly-DL-Ala-OH, H-Gly-DL-Leu-OH, H-Gly-L-Leu-OH, H-Gly-L-Val-OH,
DL-H-Ala-DL-Ala-OH, L-H-Ala-L-Ala-OH and L-H-Val-L-Val-OH were purchased from Reanal (Buda-
pest, Hungary). Silokhrom C-120 macroporous silica from Reakhim (Russia), specific surface area
about 120 m2/g, was preliminarily heated at 400 °C in the air for 3 h to remove adsorbed contamina-
tions.
The “gas–solid-phase” DOP synthesis was performed in the simple vacuum reactor used earlier1,4
.
General Procedure
Dipeptide (0.5 – 2.0 g) and silica (2 – 5 g) are placed into the reactor connected to a vacuum source
and pumped out to vacuum of about 10 Pa. The bottom zone of the reactor is heated to 180 – 210
°C for 1 – 3 h. Sublimate, containing DOP and unreacted dipeptide, condenses in the reactor cold
zone as a crust. To increase the conversion of linear dipeptide to DOP, the sublimate is returned to
the reaction zone, and the procedure is repeated; duration of the second sublimation cycle is 1 – 2 h.
Crude product is extracted from the reactor and recrystallized from water or water–ethanol.
For the ligand-exchange HPLC analyses of enantiomeric composition, DOP samples are hydro-
lyzed with 6 M HCl for 24 h at 100 °C in evacuated ampules.
RESULTS AND DISCUSSION
As starting materials only dipeptides derived from aliphatic amino acids containing no
other functional groups can be used (otherwise the synthesis can be complicated by the
formation of by-products in appreciable amounts due to increasing a number of reaction
channels on the hot silica surface). The dipeptides were sublimed in the presence of
macroporous silica at reduced pressure and temperatures of 180 – 210 °C. After the
first sublimation cycle, DOPs condensed contain small amount of unreacted dipeptides.
The process should be repeated once more to increase the conversion of dipeptides and
to obtain pure DOPs. Indeed, HPLC analyses of crude products did not reveal appreci-
able amounts of the starting dipeptides.
Mechanism of the cyclocondensation, similarly as for amino acids3, includes tran-
sient formation of a surface ester of orthosilicic acid and may be represented by
Scheme 1.
The method proposed can be considered as a rough analogue to the solid-phase DOP
synthesis5 – 8, from which any solvent and protection–deprotection steps are excluded.
The system, which is considered in the present case, has the following important
feature. At temperatures about 200 °C the silica surface still contains appreciable
amount of adsorbed water and catalyzes not only condensation of amino acids and
peptides, but also hydrolysis of the latter3. If the main process may be represented by Eq. (A)
(A)
A and A′, amino acids fragments
Collect. Czech. Chem. Commun. (Vol. 59) (1994)