Synthesis, Table of Contents Synthesis 2016; 48(24): 4564-4568DOI: 10.1055/s-0035-1562625 paper © Georg Thieme Verlag Stuttgart · New YorkA Short Synthesis of the Mould Metabolite (R)-(+)-Carolinic Acid from (S)-Lactic Acid David Linder Organisch-chemisches Laboratorium der Universität Bayreuth, Gebäude NW I, 95440 Bayreuth, Germany Email: Rainer.Schobert@uni-bayreuth.de , Rainer Schobert Organisch-chemisches Laboratorium der Universität Bayreuth, Gebäude NW I, 95440 Bayreuth, Germany Email: Rainer.Schobert@uni-bayreuth.de› Author AffiliationsRecommend Article Abstract Buy Article All articles of this category Abstract (R)-(+)-Carolinic acid was prepared in seven steps and 59% yield from inexpensive benzyl l-lactate, the configuration of which was inverted by a Mitsunobu reaction with trifluoroacetate. The resulting benzyl d-lactate was cyclised by a domino addition–Wittig alkenation reaction with Ph3PCCO. The product tetronic acid was acylated with a second equivalent of this ylide to give a 3-acylylidenetetronic acid, which was olefinated directly with tert-butyl glyoxylate. The product alkene was hydrogenated and deprotected to afford pure crystalline (R)-(+)-carolinic acid, which proved inactive against Staphylococcus aureus and Escherichia coli mutant D21f2. Key words Key wordstetronic acids - carolinic acid - Wittig reaction - natural products - stereoinversion Full Text References References 1 Haynes LJ, Plimmer JR. Q. Rev., Chem. Soc. 1960; 14: 292 2 Tejedor D, Garcia-Tellado F. Org. Prep. Proced. Int. 2004; 36: 35 3 Zografos AL, Georgiadis D. Synthesis 2006; 3157 4 Schobert R, Schlenk A. Bioorg. Med. Chem. 2008; 16: 4203 5 Georgiadis D. Tetronic Acids . In Natural Lactones and Lactams . Janecki T. Wiley-VCH; Weinheim: 2013 6 Demarcay E. Ann. Chim. Phys. 1880; 20: 422 7 Wolff L. Justus Liebigs Ann. Chem. 1896; 291: 226 8 Benary E. Ber. Dtsch. Chem. Ges. 1907; 1079 9a Clutterbuck PW, Haworth WN, Raistrick H, Smith G, Stacey M. Biochem. J. 1934; 28: 94 9b Clutterbuck PW, Raistrick H, Reuter F. Biochem. J. 1935; 29: 300 For syntheses of carlosic acid, see: 10a Bloomer JL, Kappler FE. J. Org. Chem. 1974; 39: 113 10b Svendsen A, Boll PM. J. Org. Chem. 1975; 40: 1927 10c Svendsen A, Boll PM. Tetrahedron Lett. 1974; 2821 10d Booth PM, Fox CM. J, Ley SV. Tetrahedron Lett. 1983; 24: 5143 10e Booth PM, Fox CM. J, Ley SV. J. Chem. Soc., Perkin Trans. 1 1987; 121 10f Mitsos CA, Zografos AL, Igglessi-Markopoulou O. J. Org. Chem. 2000; 65: 5852 10g Schobert R, Jagusch C. Synthesis 2005; 2421 11 For a structural elucidation of carolic acid, see: Simonsen O, Reffstrup T, Boll PM. Tetrahedron 1979; 36: 795 12 For the biosynthesis of 1 and 2, see also: Bentley R, Bhate DS, Keil JG. J. Biol. Chem. 1962; 237: 859 13 Boll PM, Sorensen E, Balieu E. Acta Chem. Scand. 1968; 22: 3251 14a Haynes LJ, Plimmer JR, Stanners AH. J. Chem. Soc. 1956; 4661 14b Haynes LJ, Plimmer JR. Chem. Ind. 1954; 37: 1147 15 Svendsen A, Boll PM. Tetrahedron 1973; 29: 4251 16 Ley SV, Trudell ML, Wadsworth DJ. Tetrahedron 1991; 47: 8285 17 Bestmann HJ, Sandmeier D. Angew. Chem., Int. Ed. Engl. 1975; 14: 634 18a Löffler J, Schobert R. J. Chem. Soc., Perkin Trans. 1 1996; 2799 18b Schobert R, Gordon GJ. Curr. Org. Chem. 2002; 6: 1181 18c Schobert R, Boeckman RK. Jr, Pero JE. Org. Synth. 2005; 82: 140 19 Jones RC. F, Begley MJ, Peterson GE, Sumaria S. J. Chem. Soc., Perkin Trans. 1 1990; 1959 20 Hori K, Arai M, Nomura K, Yoshii E. Chem. Pharm. Bull. 1987; 35: 4368 21 Sengoku T, Wierzejska J, Takahashi M, Yoda H. Synlett 2010; 2944 22 Jeong Y.-C, Moloney MG. J. Org. Chem. 2011; 76: 1342 23 Schobert R, Siegfried S, Nieuwenhuyzen M, Milius W, Hampel F. J. Chem. Soc., Perkin Trans. 1 2000; 1723 24a Schlenk A, Diestel R, Sasse F, Schobert R. Chem. Eur. J. 2010; 16: 2599 24b Harras M, Bauer T, Kempe R, Schobert R. Tetrahedron 2013; 69: 3677 25 Tapaswi PK, Choi M.-C, Jung YS, Cho HJ, Seo DJ, Ha C.-S. J. Polym. Sci., Part A: Polym. Chem. 2014; 52: 2316 26 Geny A, Agenet N, Iannazzo L, Malacria M, Aubert C, Gandon V. Angew. Chem. Int. Ed. 2009; 48: 1810 27 Blake J, Tretter JR, Juhasz GJ, Bonthrone W, Rapoport H. J. Org. Chem. 1966; 4061 28 Shin I, Lee J, Jung M, Lee W, Yoon J. J. Org. Chem. 2000; 65: 7667 29 Zhu S.-F, Chen C, Cai Y, Zhou Q.-L. Angew. Chem. Int. Ed. 2008; 47: 932 30 Schobert R, Stehle R, Walter H. Tetrahedron 2008; 64: 9401 31 For the synthesis of 14 by means of periodate, see: Våbenø J, Brisander M, Lejon T, Luthman K. J. Org. Chem. 2002; 67: 9186 32 For a synthesis of 14 through ozonolysis, see: Bishop JE, O’Connell JF, Rapoport H. J. Org. Chem. 1991; 56: 5079 Supplementary Material Supplementary Material Supporting Information
