Structure and Synthesis of Vindolicine and Derivatives.

This article describes the reaction of vindoline with formaldehyde and trimethyl orthoformate to prepare vindolicine, tris-vindolicinyl methane and higher molecular weight homologues. The synthesis of 10-formyl vindoline as an intermediate allowed further exploration of its chemistry, in particular the reaction with acetone which yielded a symmetrical dimer, which was further reacted with vindoline to give molecules containing three and four vindoline units. These molecules were characterized by NMR and for some of them (vindolicine, 10-formyl vindoline, 10-(1'-(but-1'-en-3'-one))-vindoline) by X-ray crystallography. Depending on the substitution and on the absence of axes of symmetry, the NMR spectra displayed non-equivalent spin systems for the vindoline moieties. The dimer formed from the double condensation of 10-formyl vindoline with acetone showed cytotoxic activity in the micromolar range.

(E)-4-Meth-oxy-N'-[(pyridin-4-yl)methyl-idene]benzohydrazide monohydrate.

In the title compound, C(14)H(13)N(3)O(2)·H(2)O, the azomethine double bond adopts an E conformation and the N-N=C-C torsion angle is 178.37 (19)°. The dihedral angle between the benzene and pyridine rings is 5.58 (12)° and the C atom of the meth-oxy group is roughly coplanar with its attached ring [deviation = 0.157 (3) Å]. In the crystal, the components are linked by O-H⋯O, O-H⋯N, N-H⋯O and C-H⋯O hydrogen bonds, forming (001) sheets. The water O atom accepts one N-H⋯O and two C-H⋯O inter-actions from the adjacent organic mol-ecule.

(E)-N'-(3,4-Dimeth-oxy-benzyl-idene)-4-meth-oxy-benzohydrazide.

In the title compound, C(17)H(18)N(2)O(4), the azomethine double bond adopts an E conformation with an N-N-C-C torsion angle of -178.3 (3)°. The benzene rings are almost coplaner, with a dihedral angle of 2.98 (14)° between their mean planes. In the crystal, the molecules are linked by N-H⋯O hydrogen bonds, resulting in chains of mol-ecules lying parallel to the b axis. The structure is further consolidated by rather weak C-H⋯O hydrogen-bonding inter-actions, resulting in six-membered rings about inversion centers linked into chains arranged parallel to the b axis.