N-(Fluoren-9-ylmethoxy­carbon­yl)-l-aspartic acid 4-tert-butyl ester

Kazuhiko Yamada; Daisuke Hashizume; Tadashi Shimizu

doi:10.1107/S1600536809037611

. 2009 Oct 3;65(Pt 11):o2606–o2607. doi: 10.1107/S1600536809037611

N-(Fluoren-9-ylmethoxycarbonyl)-l-aspartic acid 4-tert-butyl ester

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

PMCID: PMC2971228 PMID: 21578224

Abstract

The bond distances and bond angles of the title compound, C₂₃H₂₅NO₆, are consistent with values typically found for fluoren-9-ylmethoxycarbonyl-protected amino acids. The conformations of the backbone and the side chain are slightly different from those of l-aspartic acid. The crystal structure exhibits two intermolecular hydrogen bonds, forming a two-dimensional sheet structure parallel to the ab plane.

Related literature

For the crystal structures of aspartic acids, see: Dawson (1977 ▶); Sequeira et al. (1989 ▶); Flaig et al. (1998 ▶); Rao (1973 ▶); Wang et al. (2007 ▶); Umadevi et al. (2003 ▶); Derissen et al. (1968 ▶); Bendeif & Jelsch (2007 ▶). For the crystal structures of N-α-fluoren-9-ylmethoxycarbonyl-protected amino acids, see: Valle et al. (1984 ▶); Yamada, Hashizume & Shimizu (2008 ▶); Yamada, Hashizume, Shimizu & Deguchi (2008 ▶); Yamada, Hashizume, Shimizu, Ohiki & Yokoyama (2008 ▶).

Experimental

Crystal data

C₂₃H₂₅NO₆
M _r = 411.44
Orthorhombic,
a = 5.7166 (4) Å
b = 11.1175 (10) Å
c = 32.083 (3) Å
V = 2039.0 (3) Å³
Z = 4
Mo Kα radiation
μ = 0.10 mm⁻¹
T = 90 K
0.11 × 0.05 × 0.04 mm

Data collection

Rigaku AFC-8 diffractometer with Saturn70 CCD detector
Absorption correction: none
15110 measured reflections
2722 independent reflections
2167 reflections with I > 2σ(I)
R _int = 0.077

Refinement

R[F ² > 2σ(F ²)] = 0.059
wR(F ²) = 0.148
S = 1.13
2722 reflections
286 parameters
H-atom parameters constrained
Δρ_max = 0.29 e Å⁻³
Δρ_min = −0.27 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/S1600536809037611/fj2243sup1.cif

e-65-o2606-sup1.cif^{(22.5KB, cif)}

Structure factors: contains datablocks I. DOI: 10.1107/S1600536809037611/fj2243Isup2.hkl

e-65-o2606-Isup2.hkl^{(133.7KB, 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
O3—H3⋯O5ⁱ	0.84	1.91	2.744 (3)	172
N1—H1⋯O3ⁱⁱ	0.88	2.39	3.213 (4)	156

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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), grant No. 20750022]. TS appreciates support from the World Premier International Research Center Initiative (WPI Initiative) on Materials Nanoarchitronics (MANA) at NIMS, from MEXT.

supplementary crystallographic information

Comment

L-Aspartic acid is one of the 20 building blocks of proteins, and, in mammals, can be produced from oxaloacetate by transamination. As for the related compounds of an aspartic acid, the crystal structures of L-aspartic acid (Derissen et al.,1968; Bendeif & Jelsch, 2007), L-aspartic acid monohydrate (Umadevi et al., 2003), DL-aspartic acid (Sequeira et al., 1989; Flaig et al., 1998; Rao, 1973; Wang et al., 2007), and DL-aspartic acid hydrochloride (Dawson, 1977) have been reported so far.

Fluoren-9-ylmethoxycarbonyl (Fmoc) group is widely used for solid-phase peptide synthesis protocols as an N-α-protecting group. To our best knowledge, however,there have been only four literatures reporting crystal structures of Fmoc-protected amino acids (Valle et al., 1984; Yamada, Hashizume & Shimizu, 2008; Yamada, Hashizume, Shimizu & Deguchi, 2008; Yamada, Hashizume, Shimizu, Ohiki & Yokoyama, 2008). In this communication, the crystal structure of N-Fmoc-protected aspartic acid 4-tert-butyl ester (I) is reported.

The molecular structure of (I) is shown in Fig. 1 together with the atom labeling. The bond lengths and angles of the present molecule are in reasonable agreement with typical values found in L-aspartic acids and the related compounds. The conformations of the backbone and the side-chain, however, are slightly different from those of L-aspartic acid. The torsion angles, N1–C1–C2–C3 and N1–C1–C4–O4, are found to be 62.5 (4) and 17.0 (5)°, respectively. For L-aspartic acid, the corresponding angles are -60.3 and -39.2°, respectively. In the Fmoc-protected amino acids, the fluoren moiety takes various conformations as shown in the available literatures. In this case, the conformation of the Fmoc moiety is similar to those of Fmoc-protected isoleucine and serine.

Fig. 2 shows the crystal structure of (I). The molecules are linked via intermolecular hydrogen bonds between carboxyl and Fmoc moieties, O3–H3···O5 to form the column around the 2₁ screw axis parallel to the b axis. The columns, related by translation symmeties along the a axis each other, are joined together through weak hydrogen bonds between the amino and carboxyl groups, N1—H1···O3, two-dimensional sheet structures are formed paralell to the ab plane consequentry. The geometries of the hydrogen bonds are listed in Table 2.

Experimental

A powdered sample of the title compound was purchased from Wako Pure Chemical Industries, Ltd. (Osaka, Japan). Single crystals suitable for X-ray structure analysis could be obtained by recrystallization from ethyl acetate-dichloromethane (80:20) solution, which afforded white needle-like crystals.