Synthetic Studies of Carolacton: Enantioselective Total Synthesis of C1–C8 and C9–C19 Fragments of the Molecule

Abstract

This paper describes synthetic studies towards carolacton, a highly potent antibiotic against dental caries and endocarditis related bacterium Streptococcus mutans. The synthesis of the 12-membered lactone with a diversely functionalized keto acid side chain was accomplished by utilizing a blend of chiral pool and aldol strategies. Carbon chain C1–C8 was derived by utilizing Paterson aldol methodology and a Corey–Fuchs reaction. The C9–C19 chain was prepared by means of iterative Evans asymmetric alkylations and an E-selective cross-metathesis reaction.

Key words

Streptococcus mutans - carolacton - antibiotic - Paterson aldol reaction - cross metathesis

• References and Notes

• 1a Costerton JW, Stewart PS, Greenberg EP. Science (Washington, D.C.) 1999; 284: 1318
• 1b Costerton JW, Montanaro L, Arciola CR. Int. J. Artif. Organs 2007; 30: 757
• 2a Lynch AS, Robertson GT. Annu. Rev. Med. 2008; 59: 415
• 2b Hall-Stoodley L, Costerton JW, Stoodley P. Nat. Rev. Microbiol. 2004; 2: 95
• 2c Parcek MR, Singh PK. Annu. Rev. Microbiol. 2003; 57: 677
• 3a Kolenbrander PE, Palmer RJ. Jr, Rickard AH, Jakubovics NS, Chalmers NI, Diaz PI. Periodontology 2000 2006; 42: 47
• 3b Kolenbrander PE. Annu. Rev. Microbiol. 2000; 54: 413
• 3c Stewart PS, Costerton JW. Lancet 2001; 358: 135
• 4a Fux CA, Costerton JW, Stewart PS, Stoodley P. Trends Microbiol. 2005; 13: 34
• 4b Donlan RM, Costerton JW. Clin. Microbiol. Rev. 2002; 15: 167
• 5a Jansen R, Irschik H, Schummer D, Steinmertz H, Bock M, Schmidt T, Kirschning A, Müller R. Eur. J. Org. Chem. 2010; 7: 1284
• 5b Kunze B, Reck M, Dotsch A, Lemme A, Schummer D, Irschik H, Steinmertz H, Wagner-Döbler I. BMC Microbiol. 2010; 10: 199
• 6a Schmidt T, Kirschning A. Angew. Chem. Int. Ed. 2012; 51: 1063
• 6b Sabitha G, Shankaraiah K, Prasad MN, Yadav JS. Synthesis 2013; 45: 251
• 7a Liu L, Floreancig PE. Org. Lett. 2009; 11: 3152
• 7b Hulme AN, Howells GE. Tetrahedron Lett. 1997; 38: 8245
• 8a Maucuro AJ, Haung SL, Swern D. J. Org. Chem. 1978; 43: 2480
• 8b Balkrishna SB, Childers WB, Pinnick HW. Tetrahedron 1981; 37: 2091
• 9 Nicolaou KC, Hwang CK, Marron BE, DeFrees SA, Couladouros EA, Abe Y. J. Am. Chem. Soc. 1990; 112: 3040
• 10a Ho GJ, Mathre DJ. J. Org. Chem. 1995; 60: 2271
• 10b Paterson I, Yeung K, Watson C, Wallace RA. Tetrahedron 1998; 54: 11935
• 10c Vanderwal CD, Vosburg DA, Sorenson EJ. Org. Lett. 2001; 2: 4307
• 11a Chakraborty TK, Suresh VR. Chem. Lett. 1997; 565
• 11b Evans DA, Ennis MD, Mathre DJ. J. Am. Chem. Soc. 1982; 104: 1737
• 12 Fürstner A, Bonnekessel M, Blank JT, Radkowski K, Ing GS, Lacombe F, Gabor B, Mynott R. Chem. Eur. J. 2007; 13: 8762
• 13 Krishna PR, Srinivas P. Tetrahedron: Asymmetry 2012; 23: 769
• 14 Blackwell HE, O’Leary DJ, Chatterjee AK, Washenfelder RA, Bussmann DA, Grubbs RH. J. Am. Chem. Soc. 2000; 122: 58
• 15a Palmer AM, Jager V. Eur. J. Org. Chem. 2001; 1293
• 15b Jager V, Hafele B. Synthesis 1987; 801
• 16 Paterson I, Norcross RD, Ward RA, Romea P, Lister MA. J. Am. Chem. Soc. 1994; 116: 11287
• 17a Paterson I, Goodman JM. Tetrahedron Lett. 1989; 30: 7121
• 17b Cowden CJ, Paterson I. Org. React. 1997; 51: 1
• 17c Williams DR, Shamim K. Org. Lett. 2005; 7: 4161
• 18a Evans DA, Chapman KT. Tetrahedron Lett. 1986; 27: 5939
• 18b Evans DA, Chapman KT, Carriera EM. J. Am. Chem. Soc. 1988; 110: 3560
• 19 Dess DB, Martin JC. J. Org. Chem. 1983; 48: 4155
• 20a Corey EJ, Fuchs PL. Tetrahedron Lett. 1972; 13: 3769
• 20b Hu T, Panek JS. J. Am. Chem. Soc. 2002; 124: 11368
• 21a Lampe T, Kast R, Stoll F, Schuhmacher J. US 2011054017, 2011
• 21b Lampe T, Hahn M, Stasch J.-P, Schlemmer K.-H, Wunder F, Heitmeier S, Griebenow N, El Sheikh S, Li Volkhart M.-J, Becher E.-M, Stoll F, Knorr A. US 28971A1, 2012