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

Kazuhiko Yamada; Daisuke Hashizume; Tadashi Shimizu; Kenzo Deguchi

doi:10.1107/S1600536808021855

. 2008 Jul 19;64(Pt 8):o1533. doi: 10.1107/S1600536808021855

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

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

PMCID: PMC2962158 PMID: 21203238

Abstract

In the crystal structure of the title compound [systematic name fluoren-9-ylmethyl N-(1-carboxy-2-methylbutyl)carbamate], C₂₁H₂₃NO₄, the molecular plane of the O=C—NH—C_α unit is slightly pyramidalized. The N atom deviates from the basal plane by 0.2086 (12) Å. The O=C—N—C_α torsion angle is −17.2 (2)°, and the C—N and O=C bond lengths are 1.3675 (17) and 1.2122 (17) Å, respectively. Apparently the character of the sp ² hybrids of the molecular plane is, to some extent, reduced. The crystal structure exhibits two intermolecular hydrogen bonds (O—H⋯O and N—H⋯O), in which the hydroxy O atom acts as a donor to the carbonyl group and an acceptor of the amide group, respectively.

Related literature

For related literature on the crystal structures of N-α-fluoren-9-ylmethoxycarbonyl-protected amino acids, see: Valle et al. (1984 ▶); Yamada, Hashizume & Shimizu (2008 ▶); Yamada, Hashizume, Shimizu et al. (2008 ▶).

Experimental

Crystal data

C₂₁H₂₃NO₄
M _r = 353.40
Orthorhombic,
a = 5.3337 (2) Å
b = 13.6965 (4) Å
c = 25.2514 (9) Å
V = 1844.70 (11) Å³
Z = 4
Mo Kα radiation
μ = 0.09 mm⁻¹
T = 90 K
0.77 × 0.06 × 0.04 mm

Data collection

Rigaku AFC-8 diffractometer with Saturn70 CCD
Absorption correction: none
19825 measured reflections
3351 independent reflections
2993 reflections with I > 2σ(I)
R _int = 0.043

Refinement

R[F ² > 2σ(F ²)] = 0.034
wR(F ²) = 0.084
S = 1.03
3351 reflections
327 parameters
All H-atom parameters refined
Δρ_max = 0.23 e Å⁻³
Δρ_min = −0.18 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/S1600536808021855/is2313sup1.cif

e-64-o1533-sup1.cif^{(21.4KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536808021855/is2313Isup2.hkl

e-64-o1533-Isup2.hkl^{(164.4KB, 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
O1—H1H⋯O2ⁱ	0.88 (2)	1.77 (2)	2.6511 (14)	176 (2)
N1—H1N⋯O1ⁱⁱ	0.88 (2)	2.18 (2)	3.0433 (16)	167.6 (17)

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

Acknowledgments

KY thanks the Ministry of Education, Science, Sports, Culture and Technology (MEXT) of Japan for funding this work [Young Scientists (B), 20750022]. TS appreciates support from the World Premier International Research Center Initiative on Materials Nanoarchitronics at NIMS, from MEXT. KD acknowledges the Nanotechnology Support of MEXT.

supplementary crystallographic information

Comment

The fluoren-9-ylmethoxycarbonyl (Fmoc) group is commonly used for protecting the terminal amine of the peptide for the current solid-phase peptide synthesis protocol. This is because cleavage of the Fmoc protecting group is easily achieved by mild basis conditions, e.g., piperidine, but it is very stable under acidic conditions. The crystal structures of N-α-Fmoc-protected-L-alanine monohydrate (Valle et al., 1984), -O-t-butyl-L-serine (Yamada, Hashizume, Shimizu, Ohiki & Yokoyama, 2008) and –L-leucine (Yamada, Hashizume & Shimizu, 2008) have been studied. In this communication, we will report the structure of N-α-Fmoc-L-isoleucine, (I) (Fig. 1).

It is interesting to compare the present structure with that of the analog of the title compound, i.e., N-α-Fmoc-protected-L-leucine, (II). A large fraction of the bond distances and angles, and torsion angles of (I) are consistent with those of (II) except for the following points. First, the orientation of the carboxyl group around the C1—C6 bond is found to be opposite. The torsion angle of O2—C6—C1—N1 for (I) is -6.3 (2)°, while the corresponding angle of (II) is 159.29 (17)°. Second, the angle between the fluorine ring and the NC(=O)O plane is quite different. For example, the torsion angle of C7—O4—C8—C9 and O4—C8—C9—C10 are 121.17 (13) and -73.17 (14)°, respectively, for (I). The corresponding torsion angles of (II), on the other hand, are 93.78 (16) and 60.54 (17)°, respectively. Third, it can be seen that the O3—C7—N1—C1 plane of (I) is slightly pyramided. The N1 atom deviates from the basal plane (C1, C7, H1N) by 0.2086 (12) Å. Moreover, the distances of the N1—C7 and O3—C7 bonds are 1.3675 (17) and 1.2122 (17) Å, respectively, which are approximately 0.026 longer and 0.010 Å shorter than the corresponding bond lengths of (II), respectively. Apparently, the sp² character of the N1 atom is, to some extent, reduced.

In addition, hydrogen-bond environments are slightly different between the two Fmoc-protected L-amino acids. The crystal of (I) contains two intermolecular hydrogen bonds (Table 1), while that of (II) has three hydrogen bonds. For (I), atom O1 forms two hydrogen bonds with O2 and N1, as shown in Figure 2. The molecules, which related by translation along the a axis are assembled via the N1—H1N···O1 hydrogen bonds to form a one dimensional tape structure. The tapes around the 2₁ axis, which is parallel to the a axis, are joined together, then the column structure is formed.

Experimental

A powdered sample of the title compound (I) was purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan) and was used for the sample preparation without further purifications. Colorless needle like crystals of (I) were obtained from a saturated dichloromethane solution.