Stereospecific synthesis of d4-5-epi-8,12-iso-iPF3α-VI 55 and d4-8,12-iso-iPF3α-VI 64
Reagents and conditions:a) (i) TESCl, Et3N, DMAP, CH2Cl2, rt, 20 h, 98%; (j) Wilkinson's catalyst, catechol borane, THF, 0 °C to rt, overnight, 91%;19 (k) PT-SH, Ph3P, DIAD, THF, 0 °C - rt, 4.5 h, 97%; (l) m-CPBA, NaHCO3, CH2Cl2, rt, overnight, 96%; (m) KHMDS, 48, DME, −60 °C- rt, 8 h, 52% (E: Z = 63: 37), separated by silica gel chromatography; (n) NaBH4, ethylether/MeOH (2:1), rt, 35 min, 70%; (o) TESCl, Et3N, DMAP, CH2Cl2, 20 h, 95%; (p) DMSO, (COCl)2, Et3N, CH2Cl2, −70 °C to −20 °C, 1.5 h; (q) LiHMDS, 41, THF, −78 °C to rt, 2 h, (two steps 73%); (r) TBAF, THF, rt, overnight; (s) LiOH, iPrOH/H2O (1:1), rt, 4 h 93% (two steps); b) (t) DMSO, (COCl)2, Et3N, CH2Cl2, −70 °C to −20 °C, 1.5 h; (u) LiHMDS, 48, THF, −78 °C to rt, 2 h, (59, 8.4%, 60, 73%) (80% after I2 treatment); (v) I2, CH2Cl2, rt, 15 h, 87%; (w) EtOH, LiAlH4, (S)-Binal-H, THF, −100 °C, 45 min, 92%; (x) TBDMSCl, Et3N, DMAP, CH2Cl2, rt, overnight, 85%.