Subscribe to RSS
DOI: 10.1055/s-2006-951502
Synthesis of the ‘Northern-Hemisphere’ Fragments of the Thiopeptide Antibiotic Nosiheptide
Publication History
Publication Date:
25 October 2006 (online)
Abstract
The northern-hemisphere fragments 4 and 5 of the thiopeptide antibiotic nosiheptide have been synthesized from Boc-Glu-OBn 7 and Boc-Thr 12 in 21.8% and 16.8% overall yields, respectively.
Key words
thiazole - amino acids - heterocycles - antibiotics
- 1
Rhone-Poulenc SA. inventors; FR 1392453. - 2
Benazet F.Cartier M.Florent J.Godard C.Jung G.Lunel J.Mancy D.Pascal C.Renaut J.Tarridec P.Theilleux J.Tissier R.Dubost M.Ninet L. Experientia 1980, 36 - 3
Depaire H.Thomas J.-P.Brun A.Lukacs G. Tetrahedron Lett. 1977, 1365 - 4
Prange T.Ducruix S.Pascard C.Lunel J. Nature (London) 1977, 265: 189 - 5
Pascard C.Ducroix A.Lunel J.Prange T. J. Am. Chem. Soc. 1977, 99: 6418 - 6
Bagley MC.Dale JW.Merritt EA.Xiong X. Chem. Rev. 2005, 105: 685 - 7
Mocek U.Knaggs AR.Tsuchiya R.Nguyen T.Beale JM.Floss HG. J. Am. Chem. Soc. 1993, 115: 7557 ; and references therein - 8
Casteels M.Bekaert H.Buysse FX. Rev. Agric. 1980, 33: 1069 - 9
Horii S.Oku N. J. AOAC Int. 2000, 83: 17 - 10
Koerber-Plé K.Massiot G. Synlett 1994, 759 - 11
Shin C.Yamada Y.Hayashi K.Yonezawa Y.Umemura K.Tanji T.Yoshimura J. Heterocycles 1996, 43: 891 - 12
Bentley DJ.Fairhurst J.Gallagher PT.Manteuffel AK.Moody CJ.Pinder JL. Org. Biomol. Chem. 2004, 2: 701 - 13
Iwakawa M.Kobayashi Y.Ikuta S.Yoshimura J. Chem. Lett. 1982, 1975 - 14
Shin C.Nakamura Y.Yamada Y.Yonezawa Y.Umemura K.Yoshimura J. Bull. Chem. Soc. Jpn. 1995, 68: 3151 - 15
Umemura K.Tate T.Yamaura M.Yoshimura J.Yonezawa Y.Shin C. Synthesis 1995, 1423 - 16
Umemura K.Noda H.Yoshimura J.Konn A.Yonezawa Y.Shin CG. Tetrahedron Lett. 1997, 38: 3539 - 17
Umemura K.Noda H.Yoshimura J.Konn A.Yonezawa Y.Shin CG. Bull. Chem. Soc. Jpn. 1998, 71: 1391 - 18
Moody CJ.Bagley MC. Chem. Commun. 1998, 2049 - 19
Bagley MC.Bashford KE.Hesketh CL.Moody CJ. J. Am. Chem. Soc. 2000, 122: 3301 - 20
Hughes RA.Thompson SP.Alcaraz L.Moody CJ. Chem. Commun. 2004, 946 - 21
Hughes RA.Thompson SP.Alcaraz L.Moody CJ. J. Am. Chem. Soc. 2005, 127: 15644 - 22
Adamczyk M.Johnson DD.Reddy RE. Tetrahedron: Asymmetry 1999, 10: 775 - 23
Hanessian S.Vanasse B. Can. J. Chem. 1993, 71: 1401 - 24
Hanessian S.Margarita R. Tetrahedron Lett. 1998, 39: 5887 - 26
Singh Y.Stoermer MJ.Lucke AJ.Guthrie T.Fairlie DP. J. Am. Chem. Soc. 2005, 127: 6563 - 27
Bredenkamp MW.Holzapfel CW.van Zyl WJ. Synth. Commun. 1990, 20: 2235 - 31
Muir JC.Pattenden G.Thomas RM. Synthesis 1998, 613 - 32
Bower J.Drysdale M.Hebdon R.Jordan A.Lentzen G.Matassova N.Murchie A.Powles J.Roughley S. Bioorg. Med. Chem. Lett. 2003, 13: 2455 - 33
Silberg A.Ursu A. Rev. Roum. Chim. 1965, 10: 897
References and Notes
Analytical Data of (
S
,
S
)-1-Benzyl-5-methyl 2-
tert
-butoxycarbonylamino-4-
tert
-butyldimethylsiloxy Pentanedioate (
9).
1H NMR (300 MHz, CDCl3): δ = 7.40-7.26 (5 H, br s, ArH), 5.30 (1 H, d, J = 8.3 Hz, NH), 5.22 (1 H, d, J = 12.4 Hz, CHHPh), 5.11 (1 H, d, J = 12.4 Hz, CHHPh), 4.47 (1 H, m, CHNH), 4.28 (1 H, m, CHOSi), 3.70 (3 H, s, OMe), 2.28-2.09 (2 H, m, 3-CH2), 1.42 (9 H, s, CMe3), 0.91 (9 H, s, CMe3), 0.04 (3 H, s, Me), 0.03 (3 H, s, Me). 13C NMR (75 MHz, CDCl3): δ = 173.8 (C), 172.5 (C), 155.9 (C), 135.9 (C), 129.3 (CH), 128.8 (CH), 128.6 (CH), 80.2 (C), 69.9 (CH), 67.5 (CH2), 52.5 (Me), 51.5 (CH), 36.7 (CH2), 28.7 (Me), 26.1 (Me), 18.6 (C), -3.18 (Me).
It is established that Boc-groups can be deprotected in the presence of tert-butyl esters (for an example, see ref. 21) and of tert-butyldimethylsilyl ethers (cf. deprotection of compound 19).
29
Synthesis of (
S
,
S
)-
tert
-Butyl 2-[(1-
tert
-butoxycarbonyl-amino-3-
tert
-butyldimethylsiloxy-3-methoxy-carbonyl)propyl]thiazole-4-carboxylate (
4).
To a solution of (S,S)-2-tert-butoxycarbonylamino-4-tert-butyldimethylsiloxy-4-methoxycarbonyl-thiobutanamide (11, 1.20 g, 2.95 mmol) and tert-butyl bromopyruvate (2.30 g, 10.33 mmol) in 1,2-dimethoxyethane (42 mL) at -30 °C was added KHCO3 (1.18 g, 11.80 mmol). The mixture was stirred at -10 °C for 6 h. The colorless solid was filtered off and washed with 1,2-dimethoxyethane. The filtrate was concentrated in vacuo. The mixture was diluted in 1,2-dimethoxyethane (42 mL) and cooled at -30 °C before addition of TFAA (1.24 mL, 8.85 mmol) and 2,6-lutidine (2.06 mL, 17.70 mmol). The mixture was stirred overnight at -20 °C. The mixture was partitioned between EtOAc and brine, the organic layer separated and concentrated in vacuo. The crude product was purified by flash chromatography (EtOAc-light PE, 1:5) to give the title compound (1.33 g, 85%) as a colorless sticky solid. 1H NMR (300 MHz, CDCl3): δ = 7.93 (1 H, s, H-4), 5.77 (1 H, d, J = 8.1 Hz, NHBoc), 5.15 (1 H, m, CHOSi), 4.42 (1 H, m, CHNH), 3.70 (3 H, s, OMe), 2.51-2.40 (2 H, m, CH2), 1.57 (9 H, s, CMe3), 1.42 (9 H, s, CMe3), 0.91 (9 H, s, CMe3), 0.05 (3 H, s, Me), 0.01 (3 H, s, Me). 13C NMR (75 MHz, CDCl3): δ = 173.8 (2 × C), 160.8 (C), 155.6 (C), 149.0 (C), 126.9 (CH), 82.3 (C), 80.5 (C), 69.9 (CH), 52.5 (CH), 50.5 (Me), 39.1 (CH2), 28.7 (Me), 28.6 (Me), 26.1 (Me), 18.5 (C), -4.6 (Me), -5.1 (Me). MS (FI): m/z = 531 (14) [MH+], 473 (100), 418 (8), 417 (32), 132 (38), 57 (84).
Synthesis of Methyl 2-[(
S
)-1-(
tert
-Butoxycarbonyl-amino)-(
R
)-2-(4-methoxybenzyloxy)propyl]thiazole-4-carboxylate (
16).
To a solution of N-tert-butoxycarbonyl-O-(4-methoxy-benzyl)thiothreoninamide (15, 1.60 g, 4.51 mmol) in 1,2-dimethoxyethane (31 mL) was added at 0 °C methyl bromopyruvate (1.68 mL, 15.80 mmol) and KHCO3 (1.80 g, 18.04 mmol). The mixture was stirred 1 h at 0 °C before addition of TFAA (1.89 mL, 13.53 mmol) and 2,6-lutidine (3.15 mL, 27.06 mmol) at the same temperature. The mixture was stirred 2 h at 0 °C. The mixture was diluted in EtOAc and washed with brine. The organic layer was dried over Na2SO4 and concentrated in vacuo. The crude product was purified by flash chromatography (light PE-EtOAc, 2:1 to 1:2) to give the title compound (1.46 g, 74%) as a yellow-brown oil. 1H NMR (300 MHz, CDCl3): δ = 8.09 (1 H, s, H-4), 6.95 (2 H, d, J = 8.6 Hz, ArH), 6.75 (2 H, d, J = 8.6 Hz, ArH), 5.70 (1 H, d, J = 8.7 Hz, NHBoc), 5.00 (1 H, d, J = 8.5 Hz, CHNH), 4.39 (1 H, d, J = 11.3 Hz, CHHPh), 4.31 (1 H, m, CHHMe), 4.14 (1 H, d, J = 11.1 Hz, CHPh), 3.93 (3 H, s, OMe), 3.76 (3 H, s, OMe), 1.46 (9 H, s, CMe3), 1.27 (3 H, d, J = 6.2 Hz, Me). 13C NMR (75 MHz, CDCl3): δ = 175.0 (C), 162.3 (C), 159.6 (C), 156.1 (C), 147.3 (C), 130.1 (C), 129.8 (CH), 127.8 (CH), 114.0 (CH), 80.8 (C), 76.0 (CH), 71.5 (CH2), 58.1 (CH), 55.6 (Me), 52.8 (Me), 28.7 (Me), 16.9 (Me).
Synthesis of Methyl 2-{(
S
)-1-[2-(2-Bromothiazole-4-carbonylamino)-(
R
)-3-(
tert
-butyldimethyl-siloxy)butanoylamino]-(
Z
)-propenyl}thiazole-4-carboxylate (
5).
To a stirred solution of methyl 2-{(S)-1-[(S)-2-tert-butoxy-carbonylamino-(R)-3-(tert-butyldimethylsiloxy)butanoyl-amino]-(Z)-propenyl}thiazole-4-carboxylate (19, 482 mg, 0.94 mmol) in CH2Cl2 (13 mL) was added TFA (1.74 mL, 23.46 mmol). The mixture was stirred 30 min at 20 °C. The solvent was removed in vacuo and the residue was azeotroped with toluene. To the crude thiazole amine trifluoroacetate and 2-bromo-4-thiazolecarboxylic acid (254 mg, 1.22 mmol) in CH2Cl2 (12 mL) at 0 °C was added PyBOP (587 mg, 1.13 mmol) and N,N-diisopropylethyl-amine (0.80 mL, 4.70 mmol). The mixture was stirred 15 min at 0 °C and then overnight at r.t. The solvent was removed in vacuo. The mixture was partitioned between EtOAc and sat. solution of NaHCO3. The organic layer was washed with brine, dried over Na2SO4 and concentrated. The crude product was purified by flash chromatography (light PE-EtOAc, 1:1 to 1:2) to give the title compound (496 mg, 87%) as a colorless solid, mp 69-73 °C; [α]D
25 +24.0 (c 0.5, CHCl3). HRMS: m/z calcd for C22H31BrN4O5S2Si + H: 603.0767; found: 603.0768. IR (CH2Cl2): νmax = 3387, 3294, 2954, 2930, 2856, 1727, 1670, 1536, 1473, 1432, 1244, 1215, 1094, 1014, 838, 779 cm-1. 1H NMR (300 MHz, CDCl3): δ = 8.41 (1 H, br s, NH), 8.22 (1 H, d, J = 6.4 Hz, NH), 8.07 (2 H, s, 2 × H-4), 6.66 (1 H, q, J = 7.1 Hz, =C=CH), 4.71 (1 H, dd, J = 6.4, 3.8 Hz, CHNH), 4.57 (1 H, m, CHOSi), 3.92 (3 H, s, OMe), 1.85 (3 H, d, J = 7.1 Hz, =CMe), 1.31 (3 H, d, J = 6.4 Hz, CHMe), 0.92 (9 H, s, CMe3), 0.22 (3 H, s, Me), 0.18 (3 H, s, Me). 13C NMR (75 MHz, CDCl3): δ = 168.3 (C), 167.8 (C), 162.0 (C), 160.5 (C), 149.6 (C), 147.2 (C), 136.6 (C), 128.1 (CH), 127.7 (CH), 127.4 (CH), 68.1 (CH), 58.8 (CH), 52.8 (Me), 26.2 (Me), 19.1 (Me), 18.3 (C), 14.7 (Me), -4.3 (Me), -4.6 (Me); one quaternary C unobserved. MS (CI): m/z = 605/603 (95) [MH+], 587 (15), 525 (13), 199 (33), 133 (21), 115 (14).