tert-Butyl (2R,4aR,5aR,11aS,12R,12aR)-8-[bis­(tert-but­oxycarbon­yl)amino]-12-hydroxy-2-meth­oxy-2,10-dioxo-4,4a,5a,6,9,10,11,11a,12,12a-deca­hydro-2H-1,3,5-trioxa-6,7,9,11-tetra­aza-2λ5-phosphatetra­cene-6-carboxyl­ate methanol monosolvate monohydrate

Graeme J Gainsford; Keith Clinch; Rachel Dixon; Ashish Tiwari

doi:10.1107/S160053681202867X

. 2012 Jun 30;68(Pt 7):o2250–o2251. doi: 10.1107/S160053681202867X

tert-Butyl (2R,4aR,5aR,11aS,12R,12aR)-8-[bis(tert-butoxycarbonyl)amino]-12-hydroxy-2-methoxy-2,10-dioxo-4,4a,5a,6,9,10,11,11a,12,12a-decahydro-2H-1,3,5-trioxa-6,7,9,11-tetraaza-2λ⁵-phosphatetracene-6-carboxylate methanol monosolvate monohydrate

Graeme J Gainsford ^a,^*, Keith Clinch ^a, Rachel Dixon ^b, Ashish Tiwari ^c

PMCID: PMC3394038 PMID: 22798903

Abstract

The title compound, C₂₆H₄₀N₅O₁₃P·CH₃OH·H₂O, crystallizes with one water and one methanol molecule providing important crystal-binding interactions. The compound has the unusual feature of having two butoxycarbonyl groups bound to one N atom. The conventional attractive hydrogen bonds involving hydroxy, amine and water donors include bifurcations at both donors and acceptors with novel R ₁ ²(6) and R ₂ ¹(6) motifs. These are supplemented by C—H⋯O interactions between adjacent molecules forming chain and R ₂ ²(10) ring motifs.

Related literature

For related structures, see: Low et al. (1995 ▶, 1998 ▶, 1999 ▶). For background information, see: Veldman et al. (2010 ▶). For ring puckering parameters, see: Cremer & Pople (1975 ▶). For hydrogen-bonding graph-set nomenclature, see: Bernstein et al. (1995 ▶).

Experimental

Crystal data

C₂₆H₄₀N₅O₁₃P·CH₄O·H₂O
M _r = 711.66
Orthorhombic,
a = 10.6435 (4) Å
b = 15.9508 (13) Å
c = 21.1764 (8) Å
V = 3595.2 (3) Å³
Z = 4
Cu Kα radiation
μ = 1.31 mm⁻¹
T = 120 K
0.51 × 0.05 × 0.04 mm

Data collection

Oxford Diffraction SuperNova, Dual, Cu at zero, Atlas diffractometer
Absorption correction: multi-scan (CrysAlis PRO; Oxford Diffraction, 2007 ▶) T _min = 0.853, T _max = 1.000
20603 measured reflections
6796 independent reflections
6210 reflections with I > 2σ(I)
R _int = 0.040

Refinement

R[F ² > 2σ(F ²)] = 0.038
wR(F ²) = 0.096
S = 1.04
6796 reflections
452 parameters
2 restraints
H atoms treated by a mixture of independent and constrained refinement
Δρ_max = 0.41 e Å⁻³
Δρ_min = −0.48 e Å⁻³
Absolute structure: Flack (1983 ▶), 2985 Friedel pairs
Flack parameter: −0.02 (2)

Data collection: CrysAlis PRO (Oxford Diffraction, 2007 ▶); cell refinement: CrysAlis PRO; data reduction: CrysAlis PRO; program(s) used to solve structure: SHELXS97 (Sheldrick, 2008 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP in WinGX (Farrugia, 1999 ▶) and Mercury (Macrae et al., 2008 ▶); software used to prepare material for publication: SHELXL97 and PLATON (Spek, 2009 ▶).

Supplementary Material

Crystal structure: contains datablock(s) global, I. DOI: 10.1107/S160053681202867X/bh2437sup1.cif

e-68-o2250-sup1.cif^{(42.1KB, cif)}

Structure factors: contains datablock(s) I. DOI: 10.1107/S160053681202867X/bh2437Isup2.hkl

e-68-o2250-Isup2.hkl^{(332.6KB, hkl)}

Supplementary material file. DOI: 10.1107/S160053681202867X/bh2437Isup3.cml

Additional supplementary materials: crystallographic information; 3D view; checkCIF report

Table 1. Hydrogen-bond geometry (Å, °).

D—H⋯A	D—H	H⋯A	D⋯A	D—H⋯A
N9—H9N⋯O14	0.88	1.84	2.718 (3)	179
O12—H12O⋯O7ⁱ	0.84	2.40	3.090 (2)	139
O12—H12O⋯O9ⁱ	0.84	2.32	2.997 (2)	138
O14—H14A⋯O15	0.84 (3)	1.97 (3)	2.792 (4)	167 (4)
O14—H14B⋯O13ⁱⁱ	0.83 (4)	1.97 (4)	2.780 (3)	165 (4)
O15—H15O⋯O10	0.84	1.96	2.775 (3)	162
C4—H4B⋯O4ⁱⁱⁱ	0.99	2.31	3.142 (3)	141
C5A—H5A⋯O13^iv	1.00	2.34	3.307 (3)	162
C12A—H12A⋯O4ⁱⁱⁱ	1.00	2.38	3.200 (2)	138
C16—H16B⋯O7^v	0.98	2.44	3.230 (4)	137
C18—H18B⋯O10^vi	0.98	2.38	3.339 (4)	166

Open in a new tab

Symmetry codes: (i) Inline graphic ; (ii) ; (iii) ; (iv) ; (v) ; (vi) .

Acknowledgments

We thank Dr C. Fitchett of the University of Canterbury, New Zealand, for the data collection.

supplementary crystallographic information

Comment

The title compound is an intermediate required for the synthesis of cyclic pyranopterin monophosphate, a molecule whose absence in humans leads to a rare metabolic disorder known as molybdenum cofactor deficiency type A (Veldman et al., 2010).

The title compound crystallizes with one independent C₂₆H₄₀N₅O₁₃P molecule in the asymmetric unit with one water and one methanol molecule of crystallization (Fig. 1). This and related compounds that were prepared are prone to form merohedrally twinned crystals; this non-twinned structure is the only one successfully solved and refined to date. The absolute configuration was determined using the oxygen anomalous dispersion effect, with the Hooft y parameter value calculated as -0.012 (13) (Spek, 2009). This confirms the expected configurations at C4a (R), C5a (R), C11a (S), C12 (R) and C12a (R).

There are only three closely related structures in the Cambridge Structural Database, namely GODXEC (Low et al., 1999), PUVCIS (Low et al., 1998) and ZENSAM (Low et al., 1995) with none of these involving a fourth fused ring as found here (ring 1, atoms C4a, C12a, O1, P2, O3 & C4). A common feature of all the structures is the buckling of the fused rings progressively away from the near planar ring 4 (C6a, N7, C8, N9, C10 & C10a; see Fig. 1). A comparison of the ring parameters, and their conformational forms (Cremer & Pople, 1975) is given in Table 2 (Ring parameters) with rings 2 & 3 consisting of atoms C5a, C11a, C12, C12a, C4a, O5 and N6, C6a, C10a, N11, C11a, C5a respectively. The similarity of the dihedral angles between the planes for ZENSAM (with the same ring absolute configuration) and PUVCIS (with the inverted configuration) implies that addition of the fourth "capping" ring 1 in the stable chair conformation has not required significant conformational changes to the other rings (see Table 3: Angles between ring planes).

The binding of two BOC groups on nitrogen N8 was slightly unexpected, with the second group expected to bind to the ring nitrogen N9. Indeed, a CSD search (Version 5.33, with Feb. 2012 update) indicates that this occurrence has been reported only 19 times whereas structures with BOC single binding are numbered in the multiple 1000's.

The crystal packing consists of a set of conventional N—H···O(water) and O—H···O(methanol, P, water) hydrogen bonds (see Table 1) which include bifurcations at both donors and acceptors with novel R²₁(6) and R¹₂(6) motifs. These are supplemented by C—H···O interactions between adjacent molecules forming chain and R²₂(10) ring motifs (Bernstein et al., 1995).

Experimental

The details of the synthesis of the title compound will be published elsewhere in due course. The title compound was dissolved in methanol at ambient temperature and diethyl ether added. After 2 h the crystals were filtered off and washed with a little diethyl ether and dried at 15 Torr. The title compound was also crystallized from hot ethanol or hot ethanol and heptane mixtures followed by cooling to ambient temperature but the crystals produced in this way were twinned or were only weakly diffracting.