Evaluating the potential of vacuolar ATPase inhibitors as anticancer agents and multigram synthesis of the potent salicylihalamide analog saliphenylhalamide - PubMed (original) (raw)

Scheme 2

Reagents and conditions: (a) NaH, 4-MeOBnCl, THF (76%); (b) SO3·pyridine, DMSO, NEt3, CH2Cl2 (85%); (c) LiNH2BH3, THF (99%); (d) (COCl)2, DMSO, NEt3, CH2Cl2 (91%); (e) 4, Cy2BCl, NEt3, Et2O, 0 °C → -78 °C, add 6; MeOH, pH 7 buffer, H2O2 (93%); (f) TBSCl, imidazole, cat. DMAP, DMF (95%); (g) Me2AlCl, Bu3SnH, CH2Cl2 (86%); (h) DIAD, Ph3P, THF (82%); (i) 9 mol% PhCHRu(PCy3)2(Cl)2, CH2Cl2; (j) K2CO3, MeOH (30% for 2 steps); (k) TBSCl, imidazole, cat. DMAP, DMF (95%); (l) DDQ, CH2Cl2/H2O (18:1) (92%); (m) Dess-Martin periodinane, CH2Cl2 (95%); (n) (EtO)2P(O)CH2CO2CH2CHCH2, NaH, THF, 0 °C → rt (96%); (o) 10 mol% Pd(PPh3)3, morpholine, THF (97%); (p) (PhO)2PN3, NEt3, benzene (90%); (q) 15, benzene, reflux; then concentrate, dissolve in THF and add to LiCCPh in THF, -78 °C (90%); (r) HF·pyridine, pyridine, THF, rt.