Fig. 4: Formal synthesis of (–)-zygadenine (1) and synthesis of the alkamine of veramadine A (–)-4. | Nature Communications

Fig. 4: Formal synthesis of (–)-zygadenine (1) and synthesis of the alkamine of veramadine A (–)-4.

From: Divergent syntheses of complex Veratrum alkaloids

Fig. 4

Reagents and conditions: a TsCl, pyridine, 50 °C, 2 h then tBuOK, toluene, DMSO, –78 °C to –25 °C, 30 min, 80%. b OsO4, pyridine, THF, –40 °C, 2 h, 57% (80% brsm). c TBSCl, imidazole, DMAP, DCM, rt, overnight, 82% (68a/68b = 3:5) d BOMCl, DIPEA, TBAI, DCE, 80 °C, 1 h, 97%. e Pd/C, EtOAc, Et3N, H2 (7 MPa), rt, 20 h then TBAF, THF, 70 °C, 5 h, 65%. f NaHMDS, Bz2O, THF, 0 °C, 1 h, 97%. g IBr, MeCN, buffer (pH=7), 28 °C, 2 h, 56%. h NaHMDS, CS2, THF, –78 °C, 10 min then MeI, –78 °C, 30 min, 72%. i AIBN, nBu3SnH, benzene, reflux, 1.5 h then TBAF, THF, reflux, 3 h, quant. j DMP, NaHCO3, DCM, rt, 15 h, 84%. k Pd(OH)2/C, MeOH, H2 (1 atm), rt, 5 h. l Et2SiH2, [Ir(COE)2Cl]2, toluene, reflux, 3 h then MeCN, HF (40% aq.), rt, overnight, 62% (2 steps). brsm, yield based on the recovered starting material; BOMCl, Benzyl chloromethyl ether; DMP, Dess-Martin periodinane.

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