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DOI: 10.1055/s-0031-1290091
Facile N-Urethane-Protected α-Amino/Peptide Thioacid Preparation Using EDC and Na2S
Publikationsverlauf
Publikationsdatum:
07. Dezember 2011 (online)
Abstract
We report herein an efficient protocol for the synthesis of N-urethane-protected α-amino/peptide thioacids from their corresponding acids mediated by EDC and Na2S. The fast reaction under mild conditions enabled the process to be completed in shorter duration with good yield circumventing column purification. The chemistry is compatible with a wide variety of urethane protecting groups, side-chain functionalities, and sterically hindered amino acids.
Key words
N-urethane-protected α-amino thioacids - carbodiimides - sodium sulfide
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1a
Kent SBH. Chem. Soc. Rev. 2009, 38: 338 -
1b
Muir TW. Annu. Rev. Biochem. 2003, 72: 249 - 2
Crich D.Sasaki K.Rahaman MdY.Bowers AA. J. Org. Chem. 2009, 74: 3886 -
3a
Haung H.Carey RI. J. Peptide Res. 1998, 51: 290 -
3b
Hadad CM.Rablen PR.Wiberg KB. J. Org. Chem. 1998, 63: 8668 - 4
Barlett KN.Kolakowski RV.Katukojvala S.Williams LJ. Org. Lett. 2006, 8: 823 -
5a
Blake J. Int. J. Pept. Protein Res. 1981, 17: 273 -
5b
Yamashiro D.Blake J. Int. J. Pept. Protein Res. 1981, 18: 383 -
5c
Mitin YV.Zapevalova NP. Int. J. Pept. Protein Res. 1990, 35: 352 -
6a
Wu X.Stockdill JL.Wang P.Danishefsky SJ. J. Am. Chem. Soc. 2010, 132: 4098 -
6b
Rao Yu.Li X.Danishefsky SJ. J. Am. Chem. Soc. 2009, 131: 12924 -
7a
Park S.-D.Oh J.-H.Lim D. Tetrahedron Lett. 2002, 43: 6309 -
7b
Fazio F.Wong C.-H. Tetrahedron Lett. 2003, 44: 9083 -
7c
Mckervey MA.O’Sullivan MB.Mayers PL.Green RH. J. Chem. Soc., Chem. Commun. 1993, 94 -
8a
Shangguna N.Katukojvala S.Greenberg R.Williams LJ. J. Am. Chem. Soc. 2003, 125: 7754 -
8b
Merkx R.van Haren MJ.Rijkers Drik TS.Liskamp RMJ. J. Org. Chem. 2007, 72: 4574 - 9
Crich D.Sasaki K. Org. Lett. 2009, 11: 3514 - 10
Assem N.Natarajan A.Yudin AK. J. Am. Chem. Soc. 2010, 132: 10986 - 11
Crich D.Sharma I. Angew. Chem. Int. Ed. 2009, 48: 2355 - 12
Fu X.Jiang S.Li C.Xin J.Yang Y.Ji R. Bioorg. Med. Chem. Lett. 2007, 17: 465 - 13
Kolb J.Beck B.Almstetter M.Heck S.Herdtweck E.Dömling A. Mol. Diversity 2003, 6: 297 - 14
Yazmin T.Rosa-Bauza Berst F.Ellman JA. ChemBioChem. 2007, 8: 981 -
15a
Le H.-T.Gallard J.-F.Mayer M.Guittet E.Michelot R. Bioorg. Med. Chem. 1996, 4: 2201 -
15b
Hoeg-Jensen T.Jakobsen H.Olsen CE.Holm A. Tetrahedron Lett. 1991, 32: 7617 -
15c
Hoeg-Jensen T.Holm A.Sorensen H. Synthesis 1994, 383 -
16a
Crich D.Sana K.Guo S. Org. Lett. 2007, 9: 4423 -
16b
Crich D.Sharma I. Angew. Chem. Int. Ed. 2009, 48: 2355 - 17
Rao Y.Li X.Nagorny P.Hayashida J.Danishefsky SJ. Tetrahedron Lett. 2009, 50: 6684 - 18
Monfardini I.Huang J.-W.Beck B.Cellitti JF.Pellecchai M.Dömling A. J. Med. Chem. 2011, 54: 890 - 19
Schwabacher AW.Maynard TL. Tetrahedron Lett. 1993, 34: 1269 - 20
Tan X.-H.Yang R.Wirjo A.Liu C.-F. Tetrahedron Lett. 2008, 49: 2891 - 21
Zhang X.Lu X.-W.Liu C.-F. Tetrahedron Lett. 2008, 49: 6122 - 22
Shigenaga A.Sumikawa Y.Tsuda S.Sato S.Otaka A. Tetrahedron 2010, 66: 3290 -
23a
Wang P.Danishefsky SJ. J. Am. Chem. Soc. 2010, 132: 17045 -
23b
Wang P.Li X.Zhu J.Chen J.Yuan Y.Wu X.Danishefsky SJ. J. Am. Chem. Soc. 2011, 133: 1597 - 24
Pan J.Nelmi O.Devarie B.Xian M. Org. Lett. 2011, 13: 1092 - 25
Goyal N. Synlett 2010, 335 ; and references cited therein - 26
Sureshbabu VV.Lalithamba HS.Narandra N.Hemantha HP. Org. Biomol. Chem. 2010, 8: 835 -
27a
General Procedure for the Preparation of Peptide Acids
A solution of Nα-protected amino acid (1 mmol) in dry CH2Cl2 (5 mL) was cooled to 0 ˚C, EDC (1 mmol), HOBt (1.2 mmol), and O,N-bis-TMS-amino acid (1.5 mmol) were added. The reaction mixture was stirred for 3-4 h (TLC analysis), and then evaporation of the solvent and acidification with 1 M HCl furnished pure peptide acid.
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27b For the preparation of O,N-bis-TMS-amino
acids, see:
Tantry SJ.Vasanthakumar G.-R.Sureshbabu VV. Lett. Pept. Sci. 2003, 10: 51
References and Notes
General Procedure
for the Synthesis of Amino/Peptide Thioacids
To
a DMF solution of an acid (1.0 mmol), EDC (1.1 equiv) was added
at 0 ˚C under a nitrogen atmosphere. After stirring
for 10 min, finely ground Na2S (3 equiv) was added to
the reaction mixture which was allowed for stir for 3-4
h until the disappearance of the starting material (TLC analysis).
The residue was dissolved in EtOAc (15 mL), and the solution was
then carefully acidified at 0 ˚C to a pH of 3 by
using 1 M KHSO4. The organic layer was then immediately
separated and removed under reduced pressure. The crude product
was triturated with Et2O or recrystallized with THF-H2O
to obtain pure thioacid.
Fmoc-Ile-COSH
Yellow
solid; mp 81-83 ˚C. IR (KBr): νmax = 1689,
1739, 2550, 3342 cm-¹. R
f
= 0.39
(EtOAc-n-hexane = 60:40).
RP-HPLC: t
R = 15.2
(60-100% MeCN, 30 min). ESI-HRMS:
m/z calcd for C21H23NO3S:
392.1296 [M + Na]+;
found: 392.1290. ¹H NMR (400 MHz, CDCl3): δ = 0.88
(t, J = 5.6 Hz,
3 H), 0.98 (d, J = 3.8
Hz, 3 H), 1.12-1.24 (m, 2 H), 2.38-2.47 (m, 1
H), 4.28 (d, J = 6.7
Hz, 1 H), 4.37 (d, J = 7.1
Hz, 1 H), 4.61 (d, J = 4.4
Hz, 2 H), 5.91 (br s, 1 H), 7.43 (br s, 1 H), 7.26-7.84
(m, 8 H). ¹³C NMR (100 MHz, CDCl3): δ = 10.8, 14.3,
24.1, 37.0, 46.4, 65.9, 72.8, 125.9, 127.3, 128.6, 128.9, 139.2,
142.6, 155.2, 197.2.
Fmoc-Ala-Phe-COSH
White
solid; mp 126-128 ˚C. IR (KBr): νmax = 1681,
1748, 1768, 2549, 3328 cm-¹. R
f
= 0.53
(CHCl3-MeOH = 80:20). RP-HPLC: t
R = 11.4 (60-100% MeCN,
30 min). ESI-HRMS: m/z calcd
for C27H26N2O4S: 497.1511 [M + Na]+; found:
497.1501. ¹H NMR (400 MHz, CDCl3): δ = 1.2
(d, J = 4.8
Hz, 3 H), 2.6 (d, J = 5.6
Hz, 2 H), 2.8 (br s, 1 H), 3.38 (t, J = 7.4
Hz, 1 H), 3.6 (br s, 1 H), 3.9 (t, J = 6.9
Hz, 2 H), 4.1 (m, 1 H), 4.3 (m, 1 H), 6.32 (br s, 1 H), 7.1 (br
s, 1 H), 7.2-7.9 (m, 13 H). ¹³C
NMR (100 MHz, CDCl3): δ = 17.2, 37.4,
46.8, 51.2, 67.9, 69.7, 125.7, 126.8, 127.2, 127.9, 128.4, 128.9,
131.2, 139.1, 141.4, 143.2, 155.7, 172.1, 197.2.
Chiral-HPLC analyses were carried out employing Chiralpak IA, 250 × 4.6 mm; solvent: hexane-EtOH (7:3); flow rate: 1.0 mL/min.