Crystal structures of (±)-(1SR,5SR,6SR,7SR,10SR,11SR,13RS,14SR)-13-hydroxy-7-methoxymethoxy-11,15,18,18-tetramethyl-3-oxo-2,4-dioxatetracyclo[12.3.1.01,5.06,11]octadec-15-en-10-yl benzoate, its 13-epimer and 13-one derivative

In the title three compounds, the ring conformations of tetracycles are similar; each tetracycle adopts essentially planar, chair, half-chair and chair–chair forms. In the crystals, molecules are linked into similar chains by intermolecular hydrogen bonds.

The title compounds, C 29 H 38 O 8 Á0.25C 5 H 12 , (A), C 29 H 38 O 8 , (B), and C 29 H 36 O 8 , (C), are tetracyclic benzoates possessing a taxane skeleton with a fused dioxolane ring as the core structure. In the asymmetric unit of (A), there are two independent benzoate molecules (A and A 0 ) and a half molecule of solvent pentane disordered about an inversion center. The molecular conformations of (A), (B) and (C) are similar except for the flexible methoxymethoxy group. The cyclohexane, cyclohexene and central cyclooctane rings adopt chair, half-chair and chair-chair (extended crown) forms, respectively. The dioxolane rings are essentially planar, while the dioxolane ring of A 0 is slightly twisted from the mean plane. In the crystal of (A), intermolecular O-HÁ Á ÁO, C-HÁ Á ÁO and C-HÁ Á Á interactions link the independent benzoates alternately, forming a chain structure. In the crystals of (B) and (C), molecules are linked through O-HÁ Á ÁO and C-HÁ Á Á interactions, and C-HÁ Á ÁO hydrogen bonds, respectively, into similar chains. Further, weak intermolecular C-HÁ Á ÁO interactions connect the chains into a three-dimensional network in (A) and a sheet in (B), whereas no other interactions are observed for (C).

Chemical context
Paclitaxel is a well-known natural diterpenoid containing a taxane framework (tricyclo[9.3.1.0 3,8 ]pentadecane; Fig. 1), with potent antitumor activity (Wall & Wani, 1995). The complicated structure and significant bioactivity have attracted chemical and medicinal interest. Recently, we reported the crystal structure of the precursor for cyclization to build the taxane skeleton (Oishi et al., 2015;x4), which was obtained in a synthetic study of paclitaxel. The cyclization reaction was accomplished  to afford strained tetracyclic benzoates (A) and its 13-epimer (B), then further oxidation gave a ketone (C).

Structural commentary
The asymmetric units of the title compounds, (A), (B) and (C), are shown in Figs. 2, 3 and 4, respectively. Their molecular conformations are similar except for the flexible methoxymethoxy group (Fig. 5).

Figure 3
The asymmetric unit of compound (B) with the atom labelling. Displacement ellipsoids are drawn at the 30% probability level. Only H atoms connected to O and chiral C atoms are shown for clarity.

Figure 4
The asymmetric unit of compound (C) with the atom labelling. Displacement ellipsoids are drawn at the 30% probability level. Only H atoms connected to O and chiral C atoms are shown for clarity.

Figure 7
A packing diagram of (A) viewed down to b axis showing a threedimensional network. The chains (projected as butterfly-like shapes) are connected by the intermolecular C-HÁ Á ÁO interactions (black dashed lines). Only H atoms involved in hydrogen bonds are shown for clarity.

Figure 11
A packing diagram of (C) viewed down the c axis. Black dashed lines indicate the intermolecular C-HÁ Á ÁO interactions. Overlapped molecules (projection as a spider-like shape) do not constitute the same chain. A half body of the spider is only linked to the adjacent inverted one.

Synthesis and crystallization
The title compounds were obtained in a synthetic study on paclitaxel . The cyclohexene unit (C1/C14/ C13/C12/C11/C15) was synthesized according to a reported procedure (Nicolaou et al., 1995), and coupled with the substituted cyclohexane unit (C3-C8) prepared from 3methylanisole by a Shapiro reaction (Nicolaou et al., 1995). Further manipulation of the functional groups and cyclization reaction afforded the tetracyclic benzoates (A) and its C10epimer (B), which were oxidized into ketone (C). Each compound was purified by silica gel chromatography. Colorless crystals of (A) were grown from a benzene solution under a pentane-saturated atmosphere by slow evaporation at ambient temperature. Similarly, colorless crystals of (B) and (C) were obtained in the same manner.

Refinement
Crystal data, data collection and structure refinement details are summarized in Table 4. C-bound H atoms were positioned geometrically with C-H = 0.95-1.00 Å , and constrained to ride on their parent atoms with U iso (H) = 1.2U eq (C) or 1.5U eq (methyl C). The H atom of hydroxy group was placed guided by difference maps, with O-H = 0.84 Å and with U iso (H) = 1.5U eq (O).

sup-1
Acta Cryst. For all compounds, data collection: APEX2 (Bruker, 2014); cell refinement: SAINT (Bruker, 2014); data reduction: SAINT (Bruker, 2014); program(s) used to solve structure: SHELXS2013 (Sheldrick, 2008); program(s) used to refine structure: SHELXL2014 (Sheldrick, 2015); molecular graphics: Mercury (Macrae et al., 2006); software used to prepare material for publication: publCIF (Westrip, 2010) and PLATON (Spek, 2009).   Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger. Problematic three reflections with |I(obs)-I(calc)|/σW(I) greater than 10 (1 1 0, 9 9 11 and 5 3 11) have been omitted in the final refinement.

Hydrogen-bond geometry (Å, º)
Cg1 is the centroid of the C27-C32 benzene ring.  Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger. Problematic one reflection with |I(obs)-I(calc)|/σW(I) greater than 10 (-1 0 1) has been omitted in the final refinement.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å 2 )
x y z U iso */U eq C1 0.7169 (2) 0.18654 (10)   Refinement. Refinement of F 2 against ALL reflections. The weighted R-factor wR and goodness of fit S are based on F 2 , conventional R-factors R are based on F, with F set to zero for negative F 2 . The threshold expression of F 2 > σ(F 2 ) is used only for calculating R-factors(gt) etc. and is not relevant to the choice of reflections for refinement. R-factors based on F 2 are statistically about twice as large as those based on F, and R-factors based on ALL data will be even larger. Problematic two reflections with |I(obs)-I(calc)|/σW(I) greater than 10 (1 1 0 and 11 4 3) have been omitted in the final refinement.