N-(Fluoren-9-ylmethoxy­carbon­yl)-l-leucine

Kazuhiko Yamada; Daisuke Hashizume; Tadashi Shimizu

doi:10.1107/S1600536808014372

. 2008 May 17;64(Pt 6):o1112. doi: 10.1107/S1600536808014372

N-(Fluoren-9-ylmethoxycarbonyl)-l-leucine

Kazuhiko Yamada ^a,^*, Daisuke Hashizume ^b, Tadashi Shimizu ^a

PMCID: PMC2961627 PMID: 21202623

Abstract

The title compound [systematic name: fluoren-9-yl N-(1-carboxy-3-methylbutyl)carbamate], C₂₁H₂₃NO₄, exhibits torsion angles that vary from the typical values found in other Fmoc-protected amino acids, viz. the orientations of the fluorene and carboxyl groups [C—O—C—C = 93.8 (2) and N—C—C=O = −23.6 (2)°]. The crystal structure exhibits two intermolecular hydrogen bonds (O—H⋯O and N—H⋯O) that link the molecules into two-dimensional sheets parallel to the ab plane.

Related literature

For related literature on the structures of N-α-Fmoc-protected amino acids, see: Valle et al. (1984 ▶); Yamada et al. (2008 ▶).

Experimental

Crystal data

C₂₁H₂₃NO₄
M _r = 353.40
Orthorhombic,
a = 5.4953 (1) Å
b = 14.2700 (3) Å
c = 24.3759 (6) Å
V = 1911.51 (7) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 150 K
0.40 × 0.08 × 0.06 mm

Data collection

Rigaku AFC-8 diffractometer with Saturn70 CCD detector
Absorption correction: none
40257 measured reflections
3207 independent reflections
2906 reflections with I > 2σ(I)
R _int = 0.055

Refinement

R[F ² > 2σ(F ²)] = 0.039
wR(F ²) = 0.111
S = 1.09
3207 reflections
327 parameters
All H-atom parameters refined
Δρ_max = 0.27 e Å⁻³
Δρ_min = −0.26 e Å⁻³

Data collection: CrystalClear (Rigaku/MSC, 2005 ▶); cell refinement: HKL-2000 (Otwinowski & Minor, 1997 ▶); data reduction: HKL-2000; program(s) used to solve structure: SIR2004 (Burla et al., 2005 ▶); program(s) used to refine structure: SHELXL97 (Sheldrick, 2008 ▶); molecular graphics: ORTEP-3 for Windows (Farrugia, 1997 ▶); software used to prepare material for publication: SHELXL97.

Supplementary Material

Crystal structure: contains datablocks I, global. DOI: 10.1107/S1600536808014372/fl2198sup1.cif

e-64-o1112-sup1.cif^{(21.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808014372/fl2198Isup2.hkl

e-64-o1112-Isup2.hkl^{(157.4KB, 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
O2—H2H⋯O3ⁱ	0.85 (3)	1.82 (3)	2.6558 (17)	167 (3)
N1—H1N⋯O1ⁱⁱ	0.87 (3)	2.24 (3)	3.0751 (18)	161 (2)
C8—H8A⋯O1ⁱⁱⁱ	0.90 (2)	2.51 (2)	3.392 (2)	166 (2)

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

Acknowledgments

KY thanks the Ministry of Education, Science, Sports, Culture, and Technology (MEXT) of Japan for funding this work [Young Scientists (B), 20750022].

supplementary crystallographic information

Comment

The fluoren-9-ylmethoxycarbonyl (Fmoc) group is currently one of the most frequently used protecting groups for peptide synthesis since rapid cleavages can be readily achieved under mild basic conditions with racemization-free results. Almost all the Fmoc-protected twenty-L-amino acids are commercially available. The crystal structures of N-α-Fmoc-protected-L-alanine monohydrate (II, Valle et al., 1984) and L-serine (III, Yamada et al., 2008) have been reported so far. In the present study, we have carried out the crystal structure analysis of N-α-Fmoc-L-leucine, (I).

The bond distances and bond angles of (I, Fig. 1) are consistent with the typical values of Fmoc-protected amino acids found in the other crystal structures. Some torsion angles, however, are found to be quite different. The torsion angle of O2—C6—C1—N1, for example, is -23.6 (2)°, which is in disagreement with the previous observations in the Fmoc-protected amino acids in which the corresponding angles are 150.6° and 175.8° for (II) (Valle et al., 1984) and (III) (Yamada et al., 2008), respectively. Another example is that the torsion angle of C6—C1—N1—C7 in (I) is found to be -134.51 (15)°, which is in reasonable agreement with that of (II), -151.6°, but is inconsistent with that found in (II), -65.6°. Each angle between the fluorene ring and the NC(δb O)O plane is found to be different among the three Fmoc-protected amino acids. The torsion angles C7—O4—C8—C9 and O4—C8—C9—C10 for the title compound, for instance, are 93.78 (16)° and 60.54 (17)°, respectively. On the other hand, the corresponding angles are -179.7° and -172.1°, and 121.9° and -68.2° for (II) and (III), respectively.

Crystals of (I) contain two intermolecular hydrogen bonds (Table 1), which are formed between the carboxyl (O2—H2H) and amide oxygens (O3), and between the amide (N1—H1N) and the carbonyl (O1). The molecules are linked by O2—H2H···O3 hydrogen bonds to form a chain structure along the b axis. The linkage is supported by an additional C—H···O interaction (C8—H8A···O1). The chains are joined together by the N1—H1N···O1 hydrogen bonds to form a sheet structure parallel to the ab plane. The Fmoc and i-butyl moieties are packed between the sheets (Fig. 2).

Experimental

A powdered sample (I) was obtained from Wako Pure Chemical Industries, Ltd. (Osaka, Japan) and was used for crystallization without further purifications. Colourless needle like crystals of (I) were slowly grown from a saturated dichloromethane solution.