P. D’Arrigo et al. / Tetrahedron: Asymmetry 23 (2012) 938–944
943
3. Caboche, S.; Pupin, M.; Leclere, V.; Jacques, P.; Kucherov, G. BMC Struct. Biol.
4. Rouhi, A. M. Chem. Eng. News 2004, 82, 47–62.
4.15. General procedure for DKR of N-Boc-AA-thioesters with a
subtilisin solution
5. Schmid, A.; Dordick, J. S.; Hauer, B.; Kiener, A.; Wubbolt, M.; Witholt, B. Nature
2001, 409, 258–268.
6. Schoemake, H. E.; Mink, D.; Wubbolts, M. G. Science 2003, 299, 1694–1697.
7. Loffet, A. J. Pep. Sci. 2002, 8, 1–7.
8. Kee, S.; Jois, S. D. S. Curr. Pharm. Design 2003, 9, 1209–1224.
9. Hanessian, S.; McNaughton Smith, G.; Lombart, H. G. Tetrahedron 1997, 53,
12789–12854.
10. Wang, L.; Schultz, P. G. Angew. Chem., Int. Ed. 2005, 44, 34–66.
11. Sun, H.; Nikolovska-Coleska, Z.; Yang, C. Y.; Xu, L.; Liu, M.; Tomita, Y.; Pan, H.;
Yoshioka, Y.; Krajewski, K.; Roller, P. P.; Wang, S. J. Am. Chem. Soc. 2004, 126,
16686–16687.
The DKR of 2a and 4a was carried out in a biphasic system. The
reaction was carried out in an automatic titrator. To a solution of
D,L-N-Boc-AA-SEt (6.5 mmol) in 50 mL of MTBE, water (100 mL)
and trioctylamine (3.25 mmol) were added. The pH was adjusted
to 8 with NaOH (0.5 M) and 500 U of subtilisin was added. The
reaction was kept at pH 8 by the automatic addition of NaOH
(0.5 M), at 37 °C with vigorous mechanical stirring. After 2 days,
the consumption of NaOH 0.5 M reached 100% of the theoretical.
The water phase was separated from the organic layer and again
extracted (at pH 8) with 30 mL of diethyl ether. The aqueous phase
was brought to pH 3 by the dropwise addition of 6 M HCl. Next,
30 mL of ethyl acetate was added, and the resulting mixture was
suction-filtered through a Celite bed. The organic phase was sepa-
rated, and the aqueous layer was extracted twice with further
30 mL of ethyl acetate. The organic fractions were combined, dried,
12. Oost, T. K.; Sun, C.; Armstrong, R. C.; Al-Assaad, A. S.; Betz, S. F.; Deckwerth, T.
L.; Ding, H.; Elmore, S. W.; Meadows, R. P.; Olejniczak, E. T.; Oleksijew, A.;
Oltersdorf, T.; Rosenberg, S. H.; Shoemaker, A. R.; Tomaselli, K. J.; Zou, H.; Fesik,
S. W. J. Med. Chem. 2004, 47, 4417–4426.
13. (a) Williams, R. M. Synthesis of Optically Active
a-Amino Acids; Pergamon:
Oxford, 1989; (b) Wirth, T. Angew. Chem., Int. Ed. 1997, 36, 225–227.
14. Ma, J. A. Angew. Chem., Int. Ed. 2003, 42, 4290–4299.
15. Burk, M. J. Acc. Chem. Res. 2000, 33, 363–372.
16. Noyori, R.; Ohkuma, T. Angew. Chem., Int. Ed. 2001, 40, 40.
17. Chenault, H. K.; Dahmer, J.; Whitesides, G. M. J. Am. Chem. Soc. 1989, 111, 6354–
6364.
and evaporation of the solvent gave a quantitative amount of
Boc-AA-OH. Enantiomeric excess analyzed by chiral HPLC was
>99%. -N-Boc-AA-OH was deprotected with dioxane saturated
with HCl at 60 °C to give of -AA-OHꢁHCl as a white solid.
L-N-
18. Miyazawa, T.; Minowa, H.; Miyamoto, T. K.; Imagawa, R.; Yanagihara, T.;
Yamada, Y. Tetrahedron: Asymmetry 1997, 8, 367–370.
L
19. Chen, S.-T.; Huang, W.-H.; Wang, K. T. J. Org. Chem. 1994, 59, 7580–7581.
20. Chen, S. T.; Huang, W. H.; Wang, K. T. Chirality 1994, 6, 572–576.
21. Pugniere, M.; Domergue, N.; Castro, B.; Previero, A. Chirality 1994, 6, 472–478.
22. Sasaki, N. A.; Hachimoto, C.; Potier, P. Tetrahedron Lett. 1987, 48, 6069–6072.
23. Miyazawa, T. Amino Acids 1999, 16, 191–213.
L
4.16. (S)-2-(tert-Butoxycarbonylamino)-2-(naphthalen-1-yl)
ethanoic acid
24. Agosta, E.; Caligiuri, A.; D’Arrigo, P.; Servi, S.; Tessaro, D.; Canevotti, R.
Tetrahedron: Asymmetry 2006, 17, 1995–1999.
25. Gonalves, L. P. B.; Antunes, O. A. C.; Pinto, G. F.; Oestreicher, E. G. Tetrahedron:
Asymmetry 2000, 11, 1465–1468.
26. Li, T.; Kootstra, A. B.; Fotheringham, I. G. Org. Proc. Res. Dev. 2002, 6, 533–538.
27. Stewart, J. D. Curr. Opin. Chem. Biol. 2001, 5, 120–129.
28. Taylor, P. P.; Pantaleone, D. P.; Senkpeil, R. F.; Fotheringham, I. G. Trends
Biotechnol. 1998, 16, 412–418.
29. Hovhannisyan, N.; Harutyunyan, S.; Hovhannisyan, A.; Hambardzumyan, A.;
Chitchyan, M.; Melkumyan, M.; Oganezova, G.; Avetisyan, N. Amino Acids 2009,
37, 531–536.
30. Chrisp, P.; Goa, K. L. Drugs 1990, 39, 523–551.
31. Hirayama, R.; Yamamoto, M.; Tsukida, T.; Matsuo, K.; Obata, Y.; Sakamoto, F.;
Ikeda, S. Bioorg. Med. Chem. 1997, 5, 765–777.
32. Cooper, R.D.G.; Blaszczak, L.C.; Turner, J.R.; Conrad, P.C.; Daugherty, B.W.;
Wade, B. US 83–484128 19830412 CAN 102:148986.
33. Rivier, J. E.; Porter, J.; Rivier, C. L.; Perrin, M.; Corrigan, A.; Hook, W. A.;
Siraganian, R. P.; Vale, W. W. J. Med. Chem. 1986, 29, 1846–1851.
34. Yabe, Y.; Morita, A.; Miura, C.; Kobayashi, S.; Baba, Y. Chem. Pharm. Bull. 1977,
25, 2731–2734.
4.16.1. (
L
-N-Boc-1-naphthyl-Gly-OH)
L-2c
White solid (isopropylether), mp = 180–181 °C (dec. 183 °C),
lit.73 mp = 182–183 °C. Polarimetric analysis:
½
a 2D5
ꢃ
¼ þ90:7
(15.7 mg in 2 mL 2-propanol). 1H NMR (CDCl3) d = 1.452 (s, 9H),
5.518 (br s, 1H), 5.943 (br s, 0.5H), 6.121 (br s, 0.5H), 7.343–8.344
(m, 7H); 13C NMR (CDCl3) d = 175.596, 156.679, 134.572, 134.089,
133.914, 129.505, 128.758, 127.004, 126.532, 126.113, 125.624,
123.340, 81.528, 55.544, 28.308. ESI/MS: [M+Na]+ = 324.1. Ee as
(S)-2-amino-2-(naphthalen-1-yl)ethanoic acid hydrochloride (
L-1-
naphthyl Gly-OHꢁHCl): 96.7%; chiral HPLC analysis (method B):
Peak: L: 53.5 min (D: 22.4 min). Polarimetric analysis for (L-1-naph-
thyl Gly-OHꢁHCl): ½a D20
¼ þ26:6 (c 1.0, H2O).
ꢃ
35. Prochazka, Z.; Slaninova, J. Collect. Czech. Chem. Commun. 1995, 60, 2170–2177.
36. Hohsaka, T.; Kajihara, D.; Ashizuka, Y.; Murakami, H.; Sisido, M. J. Am. Chem.
Soc. 1999, 121, 34–40.
37. Tran, T. A.; Mattern, R. H.; Morgan, B. A.; Taylor, J. E.; Goodman, M. J. Pept. Sci.
1999, 5, 113–130.
4.17. (S)-2-(tert-Butoxycarbonylamino)-2-(naphthalen-2-yl)
ethanoic acid
38. Haug, B. E.; Skar, M. L.; Svendsen, J. S. J. Pept. Sci. 2001, 7, 425–432.
39. Ranjalahy-Rasoloarijao, L.; Lazaro, R.; Daumas, P.; Heitz, F. Int. J. Pep. Prot. Res.
1989, 33, 273–280.
40. Sobocinska, M.; Lempicka, E.; Konieczna, E.; Derdowska, L.; Lammek, B.;
Melhem, S.; Kozik, W.; Janecka, J.; Janecki, M.; Trzeciak, H. I. J. Pharm.
Pharmacol. 2000, 52, 1105–1112.
41. Tamamura, H.; Omagari, A.; Hiramatsu, K.; Oishi, S.; Habashita, H.; Kanamoto,
T.; Gotoh, K.; Yamamoto, N.; Nakashima, H.; Otaka, A.; Fujii, N. Bioorg. Med.
Chem. 2002, 10, 1417–1426.
42. Daumas, P.; Heitz, F. Biochemie 1989, 71, 77–81.
43. Lingen, H. L.; Van de Mortel, J. K. W.; Hekking, K. F. W.; Van Delft, F. L.; Sonke,
T.; Rutjes, F. P. J. T. J. Eur. Org. Chem. 2003, 317–324.
44. Zhang, X.; Ouyang, J.; Baeyens, W. R. G.; Zhai, S.; Yang, Y.; Huang, G. J. Pharm.
Biomed. Anal. 2003, 31, 1047–1057.
45. Zhang, X.; Ouyang, J.; Yang, Y. Anal. Lett. 2001, 34, 1851–1864.
46. Williams, R. M.; Hendrix, J. A. J. Org. Chem. 1990, 55, 3723–3728.
47. Reimann, E.; Voss, D. Arch. Pharmazie 1976, 309, 978–983.
48. Dave, H. R.; Hosangadi, B. D. Tetrahedron 1999, 55, 11295–11308.
49. Pugniere, M.; Castro, B.; Previero, A. Chirality 1991, 3, 170–173.
50. Syldtak, C.; Voelkel, D.; Bilitewski, U.; Krohn, K.; Hoeke, H.; Wagner, F.
Biotechnol. Lett. 1992, 14, 105–110.
4.17.1. (
L
-N-Boc-2-naphthyl-Gly-OH)
L-4c
Thioester
D,L
-4a (400 mg, 1.16 mmol), naphthalene (30 mg),
TOA (0.5 equiv, 0.58 mmol, 0.253 mL), and 2 mL subtilisin solution
were used. The conversion was monitored both by a pH-stat device
(2.4 mL of 0.5 M NaOH was added to biphasic system water/MTBE)
and by chiral HPLC analysis (method A): Peak D at 35 min; L at
37 min, naphthalene at 6 min. 4c: white solid (crystallized from
isopropylether), yield: 91.5% (1.062 mmol, 320 mg), mp = 77–
78 °C; Polarimetric analysis:
½
a 2D0
ꢃ
¼ þ158:3 (19.1 mg/2 mL 2-
PrOH). 1H NMR d = 1.364 (s, 9H), 5.275 (br s, 1 H), 5.474 (br s, 0.5
H), 5.633 (br s, 0.5 H), 7.391–8.062 (m, 7H). 13C NMR d = 173.542,
156.980, 135.700, 133.260, 133.155, 128.303, 128.026, 127.651,
126.346, 126.195, 126.069, 125.023, 81.726, 59.035, 27.962. ESI/
MS: [M+Na]+ = 324.1 Ee as (S)-2-amino-2-(naphthalen-2-yl)etha-
noic acid hydrochloride (
HPLC analysis (method B): Peak L: 32 min (D: 12 min). Polarimetric
analysis for (
L
-2-naphthyl Gly -OH⁄HCl): 99.7%; chiral
L
-naphthyl Gly-OHꢁHCl): ½a D25
¼ ꢀ8 (c 0.5, H2O).
ꢃ
51. Caligiuri, A.; D’Arrigo, P.; Gefflaut, T.; Molla, G.; Pollegioni, L.; Rosini, E.; Rossi,
C.; Servi, S. Biocat. Biotrans. 2006, 24, 409–413.
52. Sheldon, R. A. Chem. Ind. (London) 1992, 903.
53. Hanzawa, S.; Oe, S.; Tokuhisa, K.; Kawano, K.; Kobayashi, T.; Kudo, T.; Kakidani,
H. Biotechnol. Lett. 2001, 23, 589–591.
References
54. Caligiuri, A.; D’Arrigo, P.; Rosini, E.; Molla, G.; Servi, S.; Tessaro, D.; Pollegioni, L.
Adv. Synth. Catal. 2006, 348, 2183–2190.
55. D’Arrigo, P.; Cerioli, L.; Servi, S.; Tessaro, D.; Viani, F. submitted for publication.
1. Cane, D. E.; Walsh, C. T.; Khosla, C. Science 1998, 282, 63–68.
2. Strieker, M.; Marahiel, M. A. ChemBioChem 2009, 10, 607–616.