3
Scheme 4. Reagents and conditions: (a) 1.5 eq. I2, 1.5 eq. Ph3P, 1.5 eq. imidazole, CH2Cl2, r.t.; (b) 3.3 eq. vinylmagnesium chloride, 1.1 eq. CuI, 2.2 eq.
HMPA, 2.2 eq. P(OEt)3, THF, -40 to 0 °C; (c) 5 mol% Grubbs catalyst 2nd generation, CH2Cl2, r.t.; (d) H2, 10% Pd/C, EtOAc, r.t.; (e) 1.25 eq.
isobutyraldehyde, 1.25 eq. lithium diisopropylamide, 1.25 eq. HMPA, THF, -78 to 0 °C; (f) 1.2 eq. DCC, 1.9 eq. CuCl, toluene, reflux; (g) 10.0 eq. MsCl,
pyridine, r.t.; (h) 10.0 eq. KOH, MeOH, reflux; (i) 7.5 eq. LiAlH4, 2.5 eq. AlCl3, Et2O, r.t.
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reduction of (+)-23b by treatment with AlH3 resulted in the
formation of (+)-deoxy-hPTX 207O (Scheme 4). The enantiomer
(-)-deoxy-hPTX 207O was also synthesized from (+)-10 in the
same manner as shown in Scheme 4.
3. Conclusion
We have achieved the asymmetric synthesis of both
enantiomers of 8-deoxy-PTX 193H and 9-deoxy-hPTX 207O
from the common enantiopure alcohol 10. Furthermore, we are
trying to synthesize 8-desmethyl-PTXs and 9-desmethyl-hPTXs
from the enantiopure alcohol (-)-8. The antagonistic activities of
both enantiomers of these PTX alkaloids against nicotinic
acetylcholine receptors are now in progress.
Supplementary Material
Supplementary data associated with this article can be found,
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