Synthesis of covalent head-to-tail dimers of vancomycin

Tetrahedron Letters

Volumn 39, Issue 27, 1998, Pages 4917-4920

  Staroske, Thomas ^a   Williams, Dudley H ^a  

^a UNIVERSITY OF CAMBRIDGE   (United Kingdom)

Author keywords

Acylation; Antibiotics; Dimers; Molecular recognition

Indexed keywords

VANCOMYCIN;

ACYLATION; ARTICLE; BACTERICIDAL ACTIVITY; COVALENT BOND; DRUG SYNTHESIS; MOLECULAR INTERACTION; STAPHYLOCOCCUS AUREUS;

EID: 0032474791     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(98)00895-8     Document Type: Article

References (18)

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13. 13. The following abbreviations are used; PyBOP = benzotriazol-1-yl-oxy-tris-pyrrolidino-phosphonium hexafluorophosphate; PyBroP = bromo-tris-pyrrolidino-phosphonium hexafluorophosphate; HBTU = 2-(1H-benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate; DIEA = N,N-diisopropylethylamine.
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17. 17. In a typical procedure, Fmoc-β-alanine (34.6 mg, 111.1 μmol) and PyBroP (51.8 mg, 111.1 μ,mol) were dissolved in DMF (0.3 ml), and DIEA (17.6 ml, 111.1 μmol) was added. After stirring for 15 min, the solution was added to a solution of vancomycin hydrochloride (100.0 mg. 67.3 nmol) and DIEA (12.9 mg, 74.2 μmol) in DMF (4 ml). After 12h, the solvent was evaporated under reduced pressure. RP HPLC yielded 4a (44.2 mg, 35 %) and recovered 1 (65.1 mg, 58 %).
18. 18. General procedure: compound 6 (20.0 mg, 12.2 μmol) was dissolved in a mixture of DMSO (75 μl) and DMF (100 μl), and DIEA (2.5 μl, 14.3 μmol) was added. After 15 min, this solution was slowly added to a mixture of vancomycin hydrochloride (40.0 mg, 26.9 μmol) and HBTU (5.1 mg, 13.4 μmol) in DMSO (150 μl), which had been stirred for 30 min. After 45 min, the solvent was evaporated under reduced pressure. RP HPLC afforded 8 (23.3 mg, 58 %) and recovered 1 (17.1 mg, 30%).