Methyl 3 amino 3 N,4 O carbonyl 2,3,6 tride­­oxy α L lyxo hexo­pyran­oside

organic papers

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8H13NO4 doi:10.1107/S160053680601840X Acta Cryst.(2006). E62, o2490–o2492

Acta Crystallographica Section E Structure Reports Online

ISSN 1600-5368

Methyl 3-amino-3-

N

,4-

O

-carbonyl-2,3,6-trideoxy-

a

-

-

lyxo

-hexopyranoside

Matthew T. Mendlik,aRobert S. Coleman,aGuizhong Qi,b Todd L. Lowaryb‡ and Robert McDonaldb*§

a_{Department of Chemistry, The Ohio State}

University, 100 West 18th Avenue, Columbus, Ohio 43210, USA, andb_{Chemistry Department,} University of Alberta, Edmonton, Alberta, Canada T6G 2G2

‡ At the Alberta Ingenuity Centre for Carbohydrate Science

§ At the X-ray Crystallography Laboratory

Correspondence e-mail: bob.mcdonald@ualberta.ca

Key indicators

Single-crystal X-ray study

T= 193 K

Mean(C–C) = 0.003 A˚

Rfactor = 0.035

wRfactor = 0.079 Data-to-parameter ratio = 9.4

For details of how these key indicators were automatically derived from the article, see http://journals.iucr.org/e.

Received 4 May 2006 Accepted 17 May 2006

#2006 International Union of Crystallography

All rights reserved

The structure of the title compound, C8H13NO4, shows the

oxazolidone ring to be essentially planar, which forces the pyranoside ring into a2SOskew-boat conformation. The CH3

and OCH3groups both adopt pseudo-equatorial orientations.

Comment

The title compound, (I), is an intermediate in a novel route (Mendlik et al., 2006) for the preparation of glycosides of daunosamine, a sugar residue present in a number of natural products, e.g. the anticancer agent daunorubicin (II) (Arca-mone & Cassinelli, 1998). Compound (I) was obtained in excellent yield (95%) upon treatment of a solution of the aziridine-containing methyl glycoside (III) in ethyl acetate with hydrogen and palladium on carbon. The presence of the oxazolidone ring in (I) altered the conformation of the pyranose ring from the usual 4C1 chair conformer, thus

complicating the unequivocal determination of its structure by NMR spectroscopy. Fortunately, (I) could be crystallized and the X-ray structure analysis confirmed the expected structure (Fig. 1).

The solid-state structure of (I) shows the oxazolidone ring to be nearly planar [N—C3—C4—O3 = 6.3 (2)_{; atoms O3,} O4, N, C3, C4, and C8 are at most 0.0481 (14) A˚ out of the least-squares plane]. The pyranose ring is thus forced into an unusual2SOskew-boat conformation. As defined by Berceset

al.(2001), the polar coordinates for the pyranoside ring in (I) are d= 1.13,’= 259_{, = 81. In this pyranose ring} confor-mation, the methyl group attached to C5 adopts the most sterically favourable pseudo-equatorial position. The OCH3

group attached to the anomeric centre (C1) is also in the pseudo-equatorial orientation. The placement of the methoxy group pseudo-equatorially is not only favoured for steric reasons, but this orientation also allows the molecule to be stabilized by the endo-anomeric effect (Lemieux & Koto, 1974). The orientation about the C1—O2 bond is the one favoured by theexo-anomeric effect (Lemieux & Koto, 1974),

The methoxy O atom is an acceptor of a proton from the

oxazolidone NH group of an adjacent molecule

(Fig. 2), generating a hydrogen-bonded helix running parallel to thebaxis.

Experimental

Methyl 2,3-diamino-3-N-,4-O-carbonyl-2,3-N-cyclo-2,3,6-trideoxy- -l-talopyranoside, (III) (460 mg, 2.48 mmol), and 10% palladium on

carbon (400 mg, 0.62 mmol Pd) were dissolved in EtOAc (20 ml). The reaction vessel was charged with a balloon of H2gas and the reaction

mixture was stirred at room temperature for 3 h, when it was filtered through Celite. The filtrate was concentrated and the residue was filtered through silica gel (1 3 cm, 5:1 chloroform/methanol) to afford (I) as white crystalline plates (440 mg, 95%). The solid was recrystallized from 3:1 EtOAc–hexane (m.p. 390–393 K).RF0.49 (6:1,

chloroform/methanol); []D

23

47.1 (c0.4, CHCl3); IR: 2936, 2253,

1757 cm1_; 1_{H NMR (400 MHz, CDCl}

3): 6.87 (s, 1H, NH), 4.84

(app. t, 1H,J= 6.0 Hz, C1—H), 4.46 (dd, 1H,J= 1.7, 8.8 Hz, C4—H), 4.19 (app. dt, 1H,J= 4.3, 8.8 Hz, C3—H), 3.99 (dq, 1H,J= 1.7, 6.6 Hz, C5—H), 2.08 (app. dt, 1H,J= 4.9, 15.0 Hz, C2—Hb), 1.75 (ddd, 1H,

J= 4.3, 6.0, 15.0 Hz, C2—H), 1.31 (d, 3H,J= 6.6 Hz C6—H);13_C

NMR (100 MHz, CDCl3):160.0 (C O), 96.8 (C-1), 76.2 (C-4), 63.3

(C-5), 54.8 (OCH3), 47.8 (C-3), 30.0 (C-2), 15.6 (C-6); HRMS (ESI)

m/zcalculated for [C8H13NO4]Na

+_{: 210.0742, found: 210.0736.}

Crystal data

C8H13NO4

Mr= 187.19

Orthorhombic,P2₁2₁2₁

a= 5.2411 (8) A˚

b= 10.2928 (16) A˚

c= 16.760 (3) A˚

V= 904.1 (2) A˚3

Z= 4

Dx= 1.375 Mg m

3 MoKradiation

= 0.11 mm1

T= 193 (2) K Rod, colourless 0.590.120.10 mm

Data collection

Bruker SMART 1000 CCD area detector/PLATFORM diffractometer

!scans

Absorption correction: multi-scan (SADABS; Bruker, 2003)

Tmin= 0.739,Tmax= 0.989

6168 measured reflections 1114 independent reflections 940 reflections withI> 2(I)

Rint= 0.052

max= 26.4

Refinement

Refinement onF2

R[F2> 2(F2)] = 0.035

wR(F2_{) = 0.079}

S= 1.04 1114 reflections 118 parameters

H-atom parameters constrained

w= 1/[2_(F

o2) + (0.0377P)2 + 0.1378P]

whereP= (Fo2+ 2Fc2)/3 (/)max< 0.001

max= 0.15 e A˚

3 min=0.18 e A˚

3

Table 1

Selected geometric parameters (A˚ ,_).

O1—C1 1.410 (3) O1—C5 1.435 (3) O2—C1 1.424 (2) O2—C7 1.425 (3) O3—C4 1.447 (3) O3—C8 1.366 (3) O4—C8 1.212 (3)

N—C3 1.454 (3) N—C8 1.335 (3) C1—C2 1.518 (3) C2—C3 1.522 (3) C3—C4 1.545 (3) C4—C5 1.508 (3) C5—C6 1.508 (3)

C1—O1—C5 114.36 (16) C1—O2—C7 112.79 (17) C4—O3—C8 110.17 (17) C3—N—C8 113.8 (2) O1—C1—O2 110.95 (18) O1—C1—C2 113.31 (18) O2—C1—C2 105.41 (17) C1—C2—C3 112.93 (19) N—C3—C2 113.69 (19) N—C3—C4 100.78 (18)

C2—C3—C4 112.03 (19) O3—C4—C3 105.32 (17) O3—C4—C5 109.24 (18) C3—C4—C5 111.81 (18) O1—C5—C4 108.35 (18) O1—C5—C6 108.11 (19) C4—C5—C6 113.75 (19) O3—C8—N 109.4 (2) O4—C8—N 129.3 (2) O3—C8—O4 121.3 (2)

organic papers

Acta Cryst.(2006). E62, o2490–o2492 Mendliket al. _C

8H13NO4

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Figure 1

The molecular structure of (I), with displacement ellipsoids drawn at the 50% probability level.

Figure 2

Molecules are connected by N—H O hydrogen bonds (dotted lines),

creating a chain parallel to thebaxis along the 21screw operation (x,12+

Table 2

Hydrogen-bond geometry (A˚ ,_).

D—H A D—H H A D A D—H A

N—H1N O2i

0.88 2.18 2.976 (3) 150

Symmetry code: (i)x;yþ1 2;zþ

1 2.

In the absence of significant anomalous dispersion effects, Freidel pairs were merged. The assignment of the absolute stereochemistry is based on the known stereochemistries of the optically pure precursor compounds. H atoms were placed in idealized positions (N—H = 0.88 A˚ and C—H = 0.98–1.00 A˚) and these were assigned isotropic displacement parameters 1.2 timesUeqof their parent C atoms.

Data collection:SMART(Bruker, 2001); cell refinement:SAINT

(Bruker, 2003); data reduction: SAINT; program(s) used to solve structure: SHELXS97(Sheldrick, 1997); program(s) used to refine structure: SHELXL97 (Sheldrick, 1997); molecular graphics:

SHELXTL (Bruker, 2003); software used to prepare material for publication:SHELXTL.

This work was supported by the Natural Sciences and Engineering Research Council of Canada, the Alberta Inge-nuity Centre for Carbohydrate Science, and the National Institutes of Health.

References

Arcamone, F. & Cassinelli, G. (1998).Curr. Med. Chem.5, 391–419. Berces, A., Nukada, T. & Whitfield, D. M. (2001).Tetrahedron,57, 477–491. Bruker (2001).SMART. Version 5.054. Bruker AXS Inc., Madison, Wisconsin,

USA.

Bruker (2003). SADABS (Version 2.10), SAINT (Version 7.06A) and

SHELXTL(Version 6.14). Bruker AXS Inc., Madison, Wisconsin, USA. Lemieux, R. U. & Koto, S. (1974).Tetrahedron,30, 1933–1944.

Mendlik, M. T., Tao, P., Hadad, C. M., Coleman, R. S. & Lowary, T. L. (2006).J. Org. Chem.Submitted.

Sheldrick, G. M. (1997). SHELXS97 and SHELXL97. University of Go¨ttingen, Germany.

organic papers

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supporting information

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Acta Cryst. (2006). E62, o2490–o2492

supporting information

Acta Cryst. (2006). E62, o2490–o2492 [https://doi.org/10.1107/S160053680601840X]

Methyl 3-amino-3-

N

,4-

O

-carbonyl-2,3,6-trideoxy-

α

-

-

lyxo

-hexopyranoside

Matthew T. Mendlik, Robert S. Coleman, Guizhong Qi, Todd L. Lowary and Robert McDonald

methyl 3-amino-3-N,4-O-carbonyl-2,3,6-trideoxy-α-L-lyxo-hexopyranoside

Crystal data

C8H13NO4

Mr = 187.19

Orthorhombic, P212121

Hall symbol: P 2ac 2ab

a = 5.2411 (8) Å

b = 10.2928 (16) Å

c = 16.760 (3) Å

V = 904.1 (2) Å3

Z = 4

F(000) = 400

Dx = 1.375 Mg m−3

Melting point: 390 K

Mo Kα radiation, λ = 0.71073 Å Cell parameters from 1719 reflections

θ = 2.3–23.7°

µ = 0.11 mm−1

T = 193 K Rod, colourless 0.59 × 0.12 × 0.10 mm

Data collection

Bruker SMART 1000 CCD area detector/PLATFORM diffractometer

Radiation source: fine-focus sealed tube Graphite monochromator

Detector resolution: 8.192 pixels mm-1

ω scans

Absorption correction: multi-scan (SADABS; Bruker, 2003)

Tmin = 0.739, Tmax = 0.989

6168 measured reflections 1114 independent reflections 940 reflections with I > 2σ(I)

Rint = 0.052

θmax = 26.4°, θmin = 2.3°

h = −6→6

k = −12→12

l = −18→20

Refinement

Refinement on F2

Least-squares matrix: full

R[F2 _{> 2σ(F}2_{)] = 0.035}

wR(F2_{) = 0.079}

S = 1.04 1114 reflections 118 parameters 0 restraints

Primary atom site location: structure-invariant direct methods

Secondary atom site location: difference Fourier map

Hydrogen site location: inferred from neighbouring sites

H-atom parameters constrained

w = 1/[σ2_(F

o2) + (0.0377P)2 + 0.1378P]

where P = (Fo2 + 2Fc2)/3

(Δ/σ)max < 0.001

Δρmax = 0.15 e Å−3

Δρmin = −0.18 e Å−3

Special details

supporting information

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Acta Cryst. (2006). E62, o2490–o2492

Refinement. Refinement of F2 _{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 F2_{. 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 F2

are statistically about twice as large as those based on F, and R- factors based on ALL data will be even larger.

Fractional atomic coordinates and isotropic or equivalent isotropic displacement parameters (Å2₎

x y z Uiso*/Ueq

O1 0.3424 (3) 0.43448 (14) 0.39952 (9) 0.0281 (4) O2 0.1518 (3) 0.25412 (13) 0.33959 (9) 0.0283 (4) O3 0.2438 (3) 0.70392 (14) 0.43647 (9) 0.0319 (4) O4 0.3947 (4) 0.83464 (15) 0.33993 (10) 0.0396 (4) N 0.0851 (4) 0.68113 (17) 0.31545 (12) 0.0319 (5) H1N 0.0704 0.6910 0.2635 0.038* C1 0.1977 (4) 0.3902 (2) 0.33401 (14) 0.0257 (5) H1 0.2935 0.4085 0.2837 0.031* C2 −0.0644 (5) 0.4523 (2) 0.32874 (14) 0.0296 (5) H2A −0.1876 0.3987 0.3591 0.036* H2B −0.1199 0.4533 0.2723 0.036* C3 −0.0697 (5) 0.5905 (2) 0.36109 (13) 0.0287 (5) H3 −0.2497 0.6224 0.3641 0.034* C4 0.0582 (5) 0.6006 (2) 0.44389 (13) 0.0281 (5) H4 −0.0716 0.6235 0.4853 0.034* C5 0.1930 (5) 0.4765 (2) 0.46646 (14) 0.0280 (5) H5 0.0623 0.4085 0.4786 0.034* C6 0.3684 (5) 0.4903 (2) 0.53725 (16) 0.0396 (6) H6A 0.4486 0.4064 0.5488 0.047* H6B 0.2699 0.5189 0.5838 0.047* H6C 0.5006 0.5547 0.5252 0.047* C7 0.3807 (5) 0.1794 (2) 0.33806 (15) 0.0370 (6) H7A 0.3388 0.0870 0.3430 0.044* H7B 0.4906 0.2055 0.3826 0.044* H7C 0.4702 0.1945 0.2876 0.044* C8 0.2515 (5) 0.7480 (2) 0.35963 (14) 0.0292 (5)

Atomic displacement parameters (Å2₎

U11 _U22 _U33 _U12 _U13 _U23

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Acta Cryst. (2006). E62, o2490–o2492

C6 0.0475 (15) 0.0390 (14) 0.0321 (13) −0.0075 (14) −0.0072 (14) 0.0039 (11) C7 0.0397 (15) 0.0267 (12) 0.0445 (15) 0.0056 (11) 0.0004 (14) −0.0002 (11) C8 0.0313 (12) 0.0230 (11) 0.0333 (13) 0.0036 (11) −0.0027 (11) −0.0018 (10)

Geometric parameters (Å, º)

O1—C1 1.410 (3) C2—H2B 0.9900 O1—C5 1.435 (3) C3—C4 1.545 (3) O2—C1 1.424 (2) C3—H3 1.0000 O2—C7 1.425 (3) C4—C5 1.508 (3) O3—C4 1.447 (3) C4—H4 1.0000 O3—C8 1.366 (3) C5—C6 1.508 (3) O4—C8 1.212 (3) C5—H5 1.0000 N—C3 1.454 (3) C6—H6A 0.9800 N—C8 1.335 (3) C6—H6B 0.9800 N—H1N 0.8800 C6—H6C 0.9800 C1—C2 1.518 (3) C7—H7A 0.9800 C1—H1 1.0000 C7—H7B 0.9800 C2—C3 1.522 (3) C7—H7C 0.9800 C2—H2A 0.9900

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C5—O1—C1—O2 −90.4 (2) C3—N—C8—O4 −175.4 (2) C5—O1—C1—C2 28.0 (3) O1—C1—C2—C3 31.2 (3) C1—O1—C5—C4 −69.5 (2) O2—C1—C2—C3 152.66 (18) C1—O1—C5—C6 166.80 (17) C1—C2—C3—N 64.7 (3) C7—O2—C1—O1 −62.1 (2) C1—C2—C3—C4 −48.8 (3) C7—O2—C1—C2 174.87 (18) N—C3—C4—O3 6.3 (2) C8—O3—C4—C3 −4.1 (2) N—C3—C4—C5 −112.2 (2) C8—O3—C4—C5 116.1 (2) C2—C3—C4—O3 127.5 (2) C4—O3—C8—O4 −179.9 (2) C2—C3—C4—C5 9.0 (3) C4—O3—C8—N −0.2 (3) O3—C4—C5—O1 −69.3 (2) C8—N—C3—C2 −127.1 (2) O3—C4—C5—C6 50.9 (3) C8—N—C3—C4 −7.0 (3) C3—C4—C5—O1 46.9 (2) C3—N—C8—O3 4.9 (3) C3—C4—C5—C6 167.1 (2)

Hydrogen-bond geometry (Å, º)

D—H···A D—H H···A D···A D—H···A

N—H1N···O2i _{0.88 2.18 2.976 (3) 150}