8092
J. Steinreiber et al. / Tetrahedron 63 (2007) 8088–8093
J¼0.8 Hz, J¼4.4 Hz), 3.67 (d, 0.21H, anti, J¼3.8 Hz), 3.91
4.6.3. Step 1: Synthesis of (2R,3S) methyl 2-amino-3-hy-
droxy-octanoate. (2R,3S)-Methyl 2-amino-3-hydroxyocta-
noate (93 mg, yield 90%); H NMR (500 MHz, CDCl3):
(m, 1H).30
1
4.4.5. L-3-Heptylserine L-9. HPLC: OPA/MCE derivatiza-
tion, KH2PO4 buffer (50 mM, pH 8)/CH3CN¼61:39;
0.8 mL/min; tsyn¼10.5 min, tanti¼14.8 min; OPA/NAC
derivatization, KH2PO4 buffer (50 mM, pH 8)/CH3CN¼
d 0.86 (t, 3H, J¼7.0 Hz), 1.32 (m, 4H), 1.49 (m, 2H), 1.69
(m, 2H), 3.83 (s, 3H), 4.12 (m, 1H), 4.26 (m, 1H), 8.29 (s,
2H); 13C NMR (125 MHz, CDCl3): d 169.6, 70.1, 58.5,
53.8, 34.0, 31.6, 25.5, 22.8, 14.2.
72:28; 0.8 mL/min; tD ¼11.2 min, tL-syn¼15.2 min, tD
¼
-syn
-anti
17.1 min, tL-anti¼20.8 min.
4.6.4. Step 2: Synthesis of (2S,3S)-2-aminooctan -1,3-diol
D-syn-14. D-syn-14 (8 mg, yield 12%); 1H NMR (500 MHz,
DMSO-d6): d 0.84 (t, 3H, J¼7.0 Hz), 1.23 (m, 8H), 2.43 (m,
1H), 3.20 (dd, 1H, J¼11.5 Hz, J¼6.0 Hz), 3.30 (m, 1H),
3.50 (dd, 1H, J¼10.5 Hz, J¼5.5 Hz); 13C NMR
(125 MHz, DMSO-d6): d 70.7, 64.4, 57.3, 34.2, 32.2, 26.0,
22.9, 14.7.
4.4.6. L-3-Nonylserine L-10. HPLC: OPA/MCE derivatiza-
tion, KH2PO4 buffer (50 mM, pH 8)/CH3CN¼56:44;
0.8 mL/min; tsyn¼12.9 min, tanti¼17.5 min.
4.4.7. L-3-Decylserine L-11. HPLC: OPA/MCE derivatiza-
tion, KH2PO4 buffer (50 mM, pH 8)/CH3CN¼53:47;
0.8 mL/min; tsyn¼13.4 min, tanti¼17.9 min.
Acknowledgements
4.4.8. L-3-Undecylserine L-12. HPLC: OPA/MCE derivati-
zation, KH2PO4 buffer (50 mM, pH 8)/CH3CN¼50:50;
0.8 mL/min; tsyn¼14.4 min, tanti¼19.1 min.
¨
€
The Osterreichische Forschungsforderungsgesellschaft
(FFG), the Province of Styria, the Styrian Business Promo-
tion Agency (SFG), the city of Graz, and the Fonds zur
€
4.5. General procedure for the synthesis of D-serine
derivatives: synthesis of D-2-amino-3-hydroxy-4-
methylpentanoic acid D-5
Forderung der wissenschaftlichen Forschung (FWF, project
W901-B05 DK Molecular Enzymology) are acknowledged
for financial support. We would like to thank Marcel Wub-
bolts and Theo Sonke for stimulating discussions.
To a solution of DTA (23 U), MnCl2 (6 ng, 50 nmol) and
pyridoxal-50-phosphate (13 ng, 50 nmol) in 1 mL buffer
(KH2PO4, 50 mM, pH 8.0) isobutanal (7 mg, 0.1 mmol),
and glycine (75 mg, 1.0 mmol) were added. The reaction
mixture was stirred at rt for 3 h to give D-syn-5; yield 24%;
de 95% (syn); ee syn>99% (D), anti>99% (D).
References and notes
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4.6. General procedure for the synthesis of 2-amino-1,3-
diols
4. Ariga, T.; Jarvis, W. D.; Yu, R. K. J. Lipid Res. 1998, 39,
1–16.
4.6.1. Step 1: Synthesis of (2R,3S) methyl 2-amino-3-
hydroxy-4-methylpentanoate. To a mixture of D-syn-5
(135 mg, 0.92 mmol) in methanol (5 mL) thionylchloride
(1.0 g, 9 mmol) was added at 0 ꢀC and then stirred for 48 h
at rt. The solvent was removed in vacuo to form the hydro-
chloric salt of (2R,3S)-methyl 2-amino-3-hydroxy-4-methyl-
pentanoate (153 mg, yield 84%); 1H NMR (500 MHz,
CDCl3): d 1.02 (m, 6H), 1.97 (m, 2H), 3.85 (s, 3H), 4.25
(m, 1H), 4.65 (m, 1H), 8.28 (s, 2H); 13C NMR (125 MHz,
CDCl3): d 17.7, 19.7, 30.5, 53.9, 56.6, 72.2, 169.5.
5. Hannun, Y. A. Science 1996, 274, 1855–1859.
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Motoki, K.; Ueno, H.; Nakagawa, R.; Sato, H.; Kondo, E.;
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1091.
4.6.2. Step 2: Synthesis of (2S,3S)-2-amino-4-methylpen-
tan-1,3-diol D-syn-13. (2R,3S)-Methyl 2-amino-3-hydroxy-
4-methylpentanoate was dissolved in ethanol (4 mL) and
then KBH4 (182 mg, 3.4 mmol) dissolved H2O (2 mL) was
added dropwise. The reaction mixture was stirred at rt for
about 4 h. The reaction mixture was filtered and the solvent
of the filtrate was removed in vacuo. The residue was taken
up three times in MeOH (2 mL) and was filtered again. The
product was purified on a short silica column (CH2Cl2/
MeOH/NH3 (30% in H2O) gradient 75:20:5 to 10:10:1) to
14. Azuma, H.; Takao, R.; Niiro, H.; Shikata, K.; Tamagaki, S.;
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3233–3235.
1
yield 13 (20 mg, yield 18%); H NMR (500 MHz, D2O):
d 0.72 (d, 3H, J¼7.0 Hz), 0.75 (d, 3H, J¼6.5 Hz), 1.61
(m, 1H), 2.75 (m, 1H), 3.10 (m, 1H), 3.33 (dd, 1H,
J¼11.5 Hz, J¼7.0 Hz), 3.45 (dd, 1H, J¼11.5 Hz, J¼
5.5 Hz); 13C NMR (125 MHz, D2O): d 17.2, 18.9, 29.6,
52.9, 63.8, 76.6.
16. Chaudhari, V. D.; Kumar, K. S. A.; Dhavale, D. D. Org. Lett.
2005, 7, 5805–5807.