Total Synthesis of Bacterial 5-(3-Indolyl)oxazole Alkaloids: Pimprinols A–C

This paper is dedicated to the memory of Professor József Reiter.

Abstract

Pimprinols A, B, and C are bacterial 5-(3-indolyl)oxazole alkaloids that have been isolated from Streptomyces sp. Lv3–13. In this paper, we report a new synthesis of pimprinol A and the first total synthesis of pimprinol B and pimprinol C. In addition, antipodes of the naturally occurring pimprinols A and C, as well as the racemates of these two alkaloids were also prepared. In the pivotal step, the 1,3-oxazole ring was constructed by a Nicolaou’s modified Robinson–Gabriel cyclization.

Key words

oxazole - natural products - bacterial alkaloids - pimprinols A–C - total synthesis

• References

• 1 Jacobs HM, Burke BA. Alkaloids, Vol. 35. Rossi A. Academic Press; San Diego: 1989. 259–310
• 2 Davyt D, Serra G. Mar. Drugs 2010; 8: 2755
• 3 Swellmeen L. Pharma Chem. 2016; 8: 269
• 4 Joshi S, Bisht AS, Juyal D. Pharma Innovation 2017; 6: 109
• 5 Kakkar S, Narasimhan B. BMC Chem. 2019; 13: 16
• 6 Raju R, Gromyko O, Fedorenko V, Luzhetskyy A, Müller R. Tetrahedron Lett. 2012; 53: 3009
• 7 Xiang J, Wang J, Wang M, Meng X, Wu A. Tetrahedron 2014; 70: 7470
• 8 Kolasa T, Miller MJ. J. Org. Chem. 1987; 52: 4978
• 9 Testa E, Fontanella L, Mariani L. Justus Liebigs Ann. Chem. 1962; 660: 135
• 10 Leśniak S, Rachwalski M, Jarzyński S, Obijalska E. Tetrahedron: Asymmetry 2013; 24: 1336
• 11 Szabó T, Dancsó A, Ábrányi-Balogh P, Volk B, Milen M. Tetrahedron Lett. 2019; 60: 1353
• 12 Nicolaou KC, Hao J, Reddy MV, Rao PB, Rassias G, Snyder SA, Huang X, Chen DY.-K, Brenzovich WE, Giuseppone N, Giannakakou P, O’Brate A. J. Am. Chem. Soc. 2004; 126: 12897
• 13 Clayden J, Greeves N, Warren S, Wothers P. Organic Chemistry, 1st ed. Oxford University Press; Oxford: 2001: 1223
• 14 Crombie L, Jones RC. F, Palmer CJ. J. Chem. Soc., Perkin Trans. 1 1987; 333
• 15 Oruganti S, Sen S, Dahanukar VH, Ganorkar R, Chakka R. PCT Int. Appl. WO 2016108206, 2016 ; Chem. Abstr. 2016, 165, 176459.
• 16 Claffey MM, Helal CJ, Verhoest PR. PCT Int. Appl. WO 2010084438, 2010 ; Chem. Abstr. 2010, 153, 260362.
• 17 Suess B, Brockhoff A, Meyerhof W, Hofmann T. J. Agric. Food Chem. 2018; 66: 2301
• 18 Moon HR, Kim SY, Lim JW, Kim JN. Bull. Korean Chem. Soc. 2015; 36: 2773
• 19 Morisaki M, Rubio-Lightbourn J, Ikekawa N. Chem. Pharm. Bull. 1973; 21: 457
• 20 Almansour AI, Arumugam N, Kumar RS, Soliman SM. Altaf M, Ghabbour HA. Molecules 2016; 21: 724
• 21 Chudasama V, Ahern JM, Fitzmaurice RJ, Caddick S. Tetrahedron Lett. 2011; 52: 1067
• 22 Nomura T, Fukai T, Sato E, Fukushima K. Heterocycles 1981; 16: 983
• 23 Fedeor LR. J. Am. Chem. Soc. 1969; 91: 913
• 24 Nemet I, Varga-Defterdarovic L. Bioorg. Med. Chem. 2008; 16: 4551
• 25 Muratore ME, Shi L, Pilling AW, Storer RI, Dixon DJ. Chem. Commun. 2012; 48: 6351
• 26 Broberg A, Bjerketorp J, Andersson P, Sahlberg C, Levenfors JJ. Molecules 2017; 22: 1072
• 27 Miyake F, Hashimoto M, Tonsiengsom S, Yakushijin K, Horne DA. Tetrahedron 2010; 66: 4888