Abstract
The [2+2]cycloaddition of chlorosulfonyl isocyanate to vinyl and (Z)-propenyl ethers derived from the 2-O-sulfonylated (R)- and (S)-1-(furyl-2′)-1,2-ethanediols furnished the 4-alkoxy-azetidin-2-ones with a good to moderate stereoselectivity. The intramolecular alkylation of the β-lactam nitrogen atom led to the corresponding 3-(furyl-2′)- and 6-methyl-3-(furyl-2′)-clavams. The transformation of the furyl residue into an alkoxycarbonyl group led to clavams related to the natural compounds. The synthesized clavams exhibited moderate inhibitory activities against DD-peptidase 64-575 and β-lactamase (penase) as well as antifungal activities.
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References
a) Brown AG, Butlerworth D, Cole M, Hanscomb G, Hood JD, Reading C, Rolinson GN . Naturally-occurring beta-lactamase inhibitors with antibacterial activity. J Antibiot 29: 668–669 ( 1976)
b) Brown AG, Corbett DF, Goodacre J, Harbridge JB, Howarth TT, Ponsford RJ, Stirling I, King TI . Clavulanic acid and its derivatives. Structure elucidation of clavulanic acid and the preparation of dihydroclavulanic acid, isoclavulanic acid, esters and related oxidation products. J Chem Soc, Perkin Trans 1: 635–650 ( 1984)
Brown DB, Evans JR, Fletton RA . Structures of three novel β-lactams isolated from Streptomyces clavuligerus. J Chem Soc, Chem Commun 282–283 ( 1979)
Wanning M, Zahner H, Krone B, Zeeck A . Ein neues antifungisches β-lactam-antibioticum der clavam-reihe. Tetrahedron Lett 22: 2539–2540 ( 1981)
a) Pruess DL, Kellett M . Ro 22-5417, a new clavam antibiotic from Streptomyces clavuligerus. I. Discovery and biological activity. J Antibiot 36: 208–212 ( 1983)
b) Evans RH Jr, Ax H, Jacoby A, Williams TH, Jenkis E, Scanneli JP . Ro 22-5417, A new clawam antibiotic from Streptomyces clavuligerus. II. Fermentation, isolation and structure. J Antibiot 36: 213–216 ( 1983)
a) King HD, Langhärig J, Sanglier JJ . Clavamycins, new clavam antibiotics from two variants of Streptomyces hygroscopicus. I. Taxonomy of the producing organisms, fermentation, and biological activities. J Antibiot 39: 510–515 ( 1986)
b) Naegeri HV, Loosli H-R, Nussbaumer A . Clavamycins, new clavam antibiotics from two variants of Streptomyces hygroscopicus. II. Isolation and structures of clavamycins A, B and C from Streptomyces hygroscopicus NRRL 15846, and of clavamycins D, E anf F from Streptomyces hygroscopius NRRL 15879. J Antibiot 39: 516–524 ( 1986)
Veinberg G, Vorona M, Shestakova I, Kanepe I, Lukevics E . Design of β-lactams with mechanism based nonantibacterial activities. Curr Med Chem 10: 1741–1757 ( 2003)
Clauss K, Grimm D, Prossel G . β-Lactame mit über Heteroatome gebundenen Substituenten. Liebigs Ann Chem 539–560 ( 1974)
De Bernardo S, Tengi JP, Sasso GJ, Weigele M . Clavalanine (Ro 22-5417), a new clavam antibiotic from Streptomyces clavuligerus. 4. A Stereorational synthesis. J Org Chem 50: 3457–3462 ( 1985)
Müller JC, Toome V, Pruess DL, Blount JF, Weigele M . Ro 22-5417, A new clavam antibiotic from Streptomyces clavuligerus. III. Absolute stereochemistry. J Antibiot 36: 217–225 ( 1983)
Hoppe D, Hilpert T . Enantioselective total synthesis of the fungicide β-lactam antibiotic (−)-(2S,5S)-2-(2-hydroxyethyl)clavam and its (+)-(2S,5R)-epimer. Tetrahedron 43: 2467–2474 ( 1987)
Kaluza Z, Furman B, Krajewski P, Chmielewski M . Strategies for the formation of 1-dethia-1-oxa-cephams. Tetrahedron 56: 5553–5562 ( 2000)
a) Chmielewski M, Kaluża Z, Furman B . Stereocontrolled synthesis of 1-oxabicyclic β-lactam antibiotics via [2+2]cycloaddition of isocyanates to sugar vinyl ethers. J Chem Soc, Chem Commun 2689–2696 ( 1996)
b) Furman B, Kaluża Z, Lysek R, Chmielewski M . [2+2]Cycloaddition of chlorosulfonyl isocyanate to chiral vinyl ethers. Polish J Chem 73: 43–54 ( 1999)
Borsuk K, Suwin´ska K, Chmielewski M . Stereocontrolled formation of cephams from 1,3-O-ethylidene-L-erythritol. Tetrahedron: Asymmetry 12: 979–981 ( 2001)
Borsuk K, Kazimierski A, Solecka J, Urban´czyk-Lipkowska Z, Chmielewski M . Stereocontrolled formation of oxacephams from carbohydrates. Carbohydr Res 337: 2005–2015 ( 2002)
Kaluża Z, Furman B, Patel M, Chmielewski M . Asymmetric induction in [2+2]cycloaddition of chlorosulfonyl isocyanate to 1,2-O-isopropylidene-3-O-vinyl-glycofuranoses. Tetrahedron: Asymmetry 5: 2179–2186 ( 1994)
Kaluża Z, Furman B, Chmielewski M . Asymmetric induction in [2+2]cycloaddition of chlorosulfonyl isocyanate to 1,2-O-isopropylidene-5-O-vinyl-D-glycofuranoses. Tetrahedron: Asymmetry 6: 1719–1730 ( 1995)
Neuß O, Furman B, Kaluża Z, Chmielewski M . Synthesis of dioxolanylclavam from tartaric acid. Heterocycles 45: 265–270 ( 1997)
a) Cierpucha M, Solecka J, Frelek J, Szczukiewicz P, Chmielewski M . Synthesis, biological and chiroptical activity of 3-phenyl-clavams. Bioorg Med Chem 12: 405–416 ( 2004)
b) Chmielewski M, Cierpucha M, Kowalska P, Kwit M, Frelek J . Structure-chiroptical properties relationship in clavams: an experimental and theoretical study. Chirality, in press
a) Gonzales F, Lesage S, Perlin AS . Catalysis by mercuric ion of reactions of glycals with water. Carbohydr Res 42: 267–274 ( 1975)
b) Hayashi M, Kawabata H, Yamada K . Metal-catalyzed transformation of D-glucal to optically active furan diol. J Chem Soc, Chem Commun 965–966 ( 1999)
c) Agarwal A, Rani S, Vankar YD . Protic acid (HClO4 supported on silica gel)-mediated synthesis of 2,3-unsaturated-O-glucosides and a chiral furan diol from 2,3-glycals. J Org Chem 69: 6137–6140 ( 2004)
Saeed M, Ilg T, Schick M, Abbas M, Voelter W . Total synthesis and anti-leishmanial activity of R-(−)-argentilactone. Tetrahedron Lett 42: 7401–7403 ( 2001)
Prosser TJ . The Rearrangement of allyl ethers to propenyl ethers. J Am Chem Soc 83: 1701–1704 ( 1961)
Watanabe WH, Conlon LE . Homogeneous metal salt catalysis in organic reactions. I. The preparation of vinyl ethers by vinyl transetherification. J Am Chem Soc 79: 2828–2833 ( 1957)
Okimoto Y, Sakaguchi S, Ishii Y . Development of a highly efficient catalytic method for synthesis of vinyl ethers. J Am Chem Soc 124: 1590–1591 ( 2002)
Furman B, Kaluża Z, Chmielewski M . An approach to clavams and 1-oxacephams from hydroxy acids. J Org Chem 62: 3135–3139 ( 1997)
Borsuk K, Grzeszczyk B, Szczukiewicz P, Przykorska B, Frelek J, Chmielewski M . Stereoselectivity in formation of oxacephams from 1,3-alkylidene-threitols. Chirality 16: 414–421 ( 2004)
Arribas E, Carreiro C, Valdeolmillos AM . Total synthesis of (±)-clavam-2-carboxylic acid. Tetrahedron Lett 29: 1609–1612 ( 1988)
Neu HC . Structure-activity relationships: biological. In The Chemistry of β-lactams, Ed. M. I. Page, Blackie Academic & Professional, pp. 101–127 ( 1992)
Frére JM, Leyh-Bouille M, Ghuysen JM, Nieto M, Perkins HR . Exocellular DD-carboxypeptidases-transpeptidases from Streptomyces. Methods Enzymol 45: 610–636 ( 1976)
Kurzatkowski W, Solecka J, Filipek J, Kurzatkowski JD, Kurylowicz W . Streptomycetes excreting DD-carboxypeptidases. Appl Microbiol Biotechnol 33: 452–454 ( 1990)
Röhl F, Rabenhorst J, Zähner H . Biological properties and mode of action of clavams. Arch Microbiol 147: 315–320 ( 1987)
Solecka J, Kurzatkowski W . Affinity of exocellular DD-carboxypeptidase/transpeptidase from Saccharopolyspora erythraea PZH TZ-575 to beta-lactam compounds. Med Dos´w Mikrobiol 51: 151–165 ( 1999)
Solecka J, Lysek R, Furman B, Chmielewski M, Kurzatkowski W . Practical use of DD-peptidase 64-575 for assay inhibition activity of natural and synthetic β-lactam compounds. Acta Poloniae Pharmaceutica 60: 115–118 ( 2003)
O'Callaghan CH, Morris A, Kirby SM, Shingler AH . Novel method for detection of β-lactamases by using a chromogenic cephalosporin substrate. Antimicrob Agents Chemother 1: 283–288 ( 1972)
Barry AL, Pfaller MA, Rennie RP, Fuchs PC, Brown SD . Precision and accuracy of fluconazole susceptibility testing by broth microdilution, etest, and disk diffusion methods. Antimicrob Agents Chemother 46: 1781–1784 ( 2002)
Kirkpatrick WR, Turner TM, Fothergill AW, McCarthy DI, Redding SW, Rinaldi MG, Patterson TF . Fluconazole disk diffusion susceptibility testing of Candida species. J Clin Microbiol 36: 3429–3432 ( 1998)
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Cierpucha, M., Panfil, I., Danh, T. et al. Synthesis of 3-Substituted-clavams: Antifungal Properties, DD-Peptidase and β-Lactamase Inhibition. J Antibiot 60, 622–632 (2007). https://doi.org/10.1038/ja.2007.80
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DOI: https://doi.org/10.1038/ja.2007.80
