(11R)-13-[2-(4-Hydroxyphenyl)ethylamino]-4,5-epoxy-11,13-dihydrocostunolide monohydrate

The title compound (systematic name: 12-{[2-(4-hydroxyphenyl)ethyl]aminomethyl}-4,8-dimethyl-3,14-dioxatricyclo[9.3.0.02,4]tetradec-7-en-13-one monohydrate), C23H31NO4·H2O, was obtained by the reaction of tyramine with parthenolide. The configuration of the new chiral center in the title compound is R, establishing the stereospecificity of the amination reaction. The water molecule is disordered over three positions; the site occupancy factors are 0.45, 0.40 and 0.15.

Financial support from the Kentucky Lung Cancer Research Program is gratefully acknowleged.
tyramine and the cytotoxic sesquiterpene, parthenolide. This compound was found to crystallize as the monohydrate, in contrast to other structurally related parthenolide analogs (Nasim et al., 2007a(Nasim et al., , 2007b. The side-chain was found to be in a fully extented conformation. The absolute stereochemistry of the newly formed methine carbon at C-11 was found to be R, which is typical of such amine adducts of parthenolide (Nasim et al., 2007a(Nasim et al., , 2007b. Bond distances and angles within the molecule were quite regular with average normal bond lengths (Allen et al., 1987). A weak hydrogen bond (Desiraju et al., 1999) is observed between N-1H and O3 of the carbonyl oxygen of the 5-membered lactone ring (2.22 (3) A°, 2.97 (3) A°, 137.0 (2) °) (Table 1),

Experimental
The title compound was prepared utilizing the general procedure reported earlier (Nasim et al., 2007a(Nasim et al., , 2007b Cell parameters from 5637 reflections a = 10.8307 (7)

Refinement
Refinement on F 2 Hydrogen site location: inferred from neighbouring sites Least-squares matrix: full H atoms treated by a mixture of independent and constrained refinement as large as those based on F, and R-factors based on ALL data will be even larger.
CIFCHECK squawks about H atoms being detached from their oxygen atom in the third disorder component of the water. They are are in fact 0.85Å from O1W3, but the occupancy factor is only 0.15. They were included so as to get the atom count correct, and no claim is made for their veracity.
This three-component disorder for the water is consistent with the fact that the crystals appeared to be cracking due to solvent loss.
The actual crystal chosen was carefully cut so that it did not have any cracks, but still it is quite likely that the three-part disorder is related to this observed tendency for these crystals to dry and crack.
_publ_section_exptl_refinement: H atoms were found in difference Fourier maps and subsequently placed in idealized positions with constrained C-H distances of 0.95 Å (C sp2 -H), 1.00 Å (R 3 CH), 0.99 Å (R 2 CH 2 ), 0.98 Å (RCH 3 ), 0.84 Å (OH) and 0.85 Å (OH 2 ) except for the NH hydrogen coordinates, which were refined. Hydrogen atom U iso (H) values were set to 1.2U eq or 1.5U eq (RCH 3 , OH, OH 2 ) of the attached atom. Since the water molecule was severely disordered the hydrogen atoms were placed in reasonable but not necessarily correct positions, and were subsequently fixed. supplementary materials sup-9