2,6-Dide­oxy-2,6-imino-l-glycero-d-ido-heptitol

Sarah F Jenkinson; K Victoria Booth; Scott Newberry; George W J Fleet; Ken Izumori; Kenji Morimoto; Robert J Nash; Laurence Jones; David J Watkin; Amber L Thompson

doi:10.1107/S1600536809025045

. 2009 Jul 4;65(Pt 8):o1755–o1756. doi: 10.1107/S1600536809025045

2,6-Dideoxy-2,6-imino-l-glycero-d-ido-heptitol

Sarah F Jenkinson ^a,^*, K Victoria Booth ^a, Scott Newberry ^a, George W J Fleet ^a, Ken Izumori ^b, Kenji Morimoto ^b, Robert J Nash ^c, Laurence Jones ^c, David J Watkin ^d, Amber L Thompson ^d

PMCID: PMC2977159 PMID: 21583466

Abstract

The title molecule, C₇H₁₅NO₅, the major product from selective enzymatic oxidation followed by hydrogenolysis of the corresponding azidoheptitol, was found by X-ray crystallography to exisit in a chair conformation with three axial hydroxyl groups. One of the hydroxymethyl groups is disordered over two sets of sites in a 0.590 (3):0.410 (3) ratio. In the crystal, O—H⋯O, O—H⋯(O,O), O—H⋯N and N—H⋯O hydrogen bonding occurs.

Related literature

For the synthesis of homonojirimycin derivatives, see: Compain et al. (2009 ▶); Asano et al. (2000 ▶); Watson et al. (2001 ▶); Ikeda et al. (2000 ▶); Asano et al. (1998 ▶); Kite et al. (1988 ▶); Dondoni & Nuzzi (2006 ▶). For the biological applications of homonojirimycin derivatives, see: Compain et al. (2006 ▶). For related literature on Izumoring technology, see: Izumori et al. (2002 ▶, 2006 ▶); Yoshihara et al. (2008 ▶); Rao et al. (2008 ▶); Jones et al. (2008 ▶). For related crystallography literature, see: Görbitz (1999 ▶).

Experimental

Crystal data

C₇H₁₅NO₅
M _r = 193.20
Monoclinic,
a = 10.2907 (3) Å
b = 7.6035 (3) Å
c = 11.0057 (3) Å
β = 91.8668 (16)°
V = 860.69 (5) Å³
Z = 4
Mo Kα radiation
μ = 0.13 mm⁻¹
T = 150 K
0.50 × 0.50 × 0.20 mm

Data collection

Area diffractometer
Absorption correction: multi-scan (DENZO/SCALEPACK; Otwinowski & Minor, 1997 ▶) T _min = 0.81, T _max = 0.98
7892 measured reflections
1944 independent reflections
1609 reflections with I > 2σ(I)
R _int = 0.030

Refinement

R[F ² > 2σ(F ²)] = 0.039
wR(F ²) = 0.097
S = 0.99
1944 reflections
137 parameters
H-atom parameters constrained
Δρ_max = 0.33 e Å⁻³
Δρ_min = −0.32 e Å⁻³

Data collection: COLLECT (Nonius, 2001 ▶); cell refinement: DENZO/SCALEPACK (Otwinowski & Minor, 1997 ▶); data reduction: DENZO/SCALEPACK; program(s) used to solve structure: SIR92 (Altomare et al., 1994 ▶); program(s) used to refine structure: CRYSTALS (Betteridge et al., 2003 ▶); molecular graphics: CAMERON (Watkin et al., 1996 ▶); software used to prepare material for publication: CRYSTALS.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536809025045/lh2854sup1.cif

e-65-o1755-sup1.cif^{(16.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809025045/lh2854Isup2.hkl

e-65-o1755-Isup2.hkl^{(97.5KB, hkl)}

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
O14—H141⋯O16ⁱ	0.80	1.89	2.684 (3)	170
O16—H161⋯N1ⁱⁱ	0.84	1.96	2.793 (3)	171
N1—H11⋯O12ⁱⁱⁱ	0.84	2.17	2.996 (3)	165
O13—H131⋯O8^iv	0.79	1.97	2.739 (3)	165
O13—H131⋯O11^iv	0.79	2.08	2.824 (3)	158
O12—H121⋯O14^v	0.85	2.39	3.052 (3)	136
O8—H81⋯O13^vi	0.83	2.00	2.805 (3)	164
O11—H111⋯O13^vi	0.82	2.02	2.843 (3)	173

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

Acknowledgments

This work was supported in part by the Program for Promotion of Basic Research Activities for Innovative Biosciences (PROBRAIN).

supplementary crystallographic information

Comment

The methodology developed by Izumori (2002, 2006) for the interconversion of tetroses, pentoses and hexoses by enzymatic oxidation, inversion at C3 with a single epimerase, and reduction to the aldose has been seen to be generally applicable for the 1-deoxy ketohexoses (Yoshihara et al., 2008) and branched sugars (Rao et al., 2008; Jones et al., 2008). This methodology has now also been applied to azido heptitols and thus to the synthesis of 2,6-dideoxy-2,6-iminoheptitols (homonojirimycins); these seven carbon imino sugars (Compain et al., 2009; Asano et al., 2000; Watson et al., 2001), are a family of glycosidase inhibitors. A number of homonojrimycins have been isolated as natural products from medicinal plants (Ikeda et al., 2000; Asano et al., 1998; Kite et al., 1988). Other piperidines with all the ring hydroxyl groups axial have been shown to be very powerful glycosidase inhibitors (Compain et al., 2006).

The azido heptitol 1 was synthesized from readily available D-glycero-D-gulo-heptono-1,4-lactone and underwent selective enzymatic oxidation to the ketose 2 followed by hydrogenation with closure on either face of the ketone to generate the imino sugars 3 and 4 (Fig. 1). The major product was found to be the symmetrical homonorjirimycin 3 and its structure was confirmed by X-ray crystallography.

The X-ray structure shows that the compound adopts a chair conformation with 3 axial hydroxyl substituents (Fig. 2). There is significant disorder in the structure with one of the equatorial hydroxymethyl groups occupying two possible sites each of which is able to form a hydrogen bond.The crystal exists as an extensively hydrogen bonded lattice with each molecule acting as a donor and an acceptor for 8 hydrogen bonds (Fig. 3).

Experimental

The title compound was recrystallized from mixture of 95% ethanol and 5% water layered with acetone: m.p. 442–445 K (free base); [α]_D²⁵ 0.0 (c, 1.27 in MeOH) (HCl salt). All other data was consistent with the literature data for the HCl salt (Dondoni & Nuzzi, 2006).