CONTRIBUTION TO CINCHONA ALKALOIDS CHEMISTRY

Ph.D. Thesis Abstract Contribution to cinchona alkaloids chemistry
.
Synthesis of [3R,4S,8S,9R]-methansulfonyloxi-5-vinyl-cinconan (O-mesylcinchonine) 9
was performed by the reaction of cinchonine 3 with MsCl in the presence of triethylamine,[141]
the reaction is presented in scheme 2.2.
N
Scheme 2.2
OH
N
MsCl, Et 2N,
0 o C, 4 ore
3 9
For obtaining O-mesylcinchonine 9, 1 mol cinchonine (CN) 3 reacts with 1,5 moli
mesylchloride (MsCl) in tetrahydrofuran (THF) used as a solvent. The reaction takes place in the
presence of excess triethylamine (TEA) (CN:TEA=1:2,2 moli). The end of the reaction will be
verified by thin layer cromatography. The reaction products are purified by column
cromatography. After the evaporation of the solvent we obtain a reaction yield of 76,6%. O-
mesylcinchonine appears like beige acicular crystals. The product was characterized by H-RMN,
IR and elemental analysis.
In order to determine the optimum ratio of reactants some experiments were performed
using various quantities of reactants. The results are presented in table 2.2, figure 2.2.
7
N
OMs
Table 2.2. The reaction conditions for obtaining O-mesilcinconinei 9
Nr.
probă
Raport molar
CN: MsCl
Solvent
Timp de
reacție (ore)
Temp
(°C)
N
Rand.
(%)
1 1:1 THF 3 0 49
2 1:1,3 THF 4 0 63
3 1:1,5 THF 4 0 76
4 1:1,8 THF 5 0 79
The best results were obtained when experiments were performed with a molar ratio of
reactants cinconina:MsCl of 1:1,5. By increasing the quantity of MsCl, above an excess of 50%,
we do not obtain a significant increase in yield. In the same reaction conditions we obtainedan