Preparation of Divergent Intermediates and Convergent Synthesis of Phytofluene

This paper is dedicated to the late Prof. Synnøve Liaaen-Jensen for her dedication to carotenoid research.

Abstract

Practical synthetic methods for biogenetically and pharmaceutically important phytofluene were developed through the divergent preparation of key C₂₀ substrates from a common intermediate and convergent synthesis by Wittig and Julia–Kocienski olefinations. Expeditious synthesis of phytofluene was also proposed based on the Julia sulfone-mediated chain-extension and double elimination method. Stereochemical outcomes of these olefination methods for phytofluene were compared and the Julia–Kocienski method was the mildest and most efficient reaction condition to produce all-(E)-phytofluene. Complete ¹H and ¹³C NMR analysis of all-(E)-phytofluene is reported for the first time. Phytofluene undergoes facile thermal isomerization to other Z-isomers above room temperature, which was also confirmed with a C₃₀ phytofluene homologue.

Key words

carotenoids - isomerization - olefination - phytofluene - sulfones - total synthesis

Publikationsverlauf

Eingereicht: 17. Februar 2023

Angenommen nach Revision: 15. März 2023

Accepted Manuscript online:
15. März 2023

Artikel online veröffentlicht:
19. April 2023

• References

• 1 Kotake-Nara E, Miyashita K, Nagao A, Kushiro M, Zhang H, Sugawara T. J. Nutr. 2001; 131: 3303
• 2 De Spirt S, Lutter K, Stahl W. Curr. Nutr. Food Sci. 2010; 6: 36
• 3 Aust O, Stahl W, Sies H, Tronnier H, Heinrich U. Int. J. Vitam. Nutr. Res. 2005; 75: 54
• 4 Dogbo O, Laferrière A, D’Harlingue A, Camara B. Proc. Natl. Acad. Sci. U. S. A. 1988; 85: 7054
• 5a Goodwin TW, Jamikorn M. Nature 1952; 170: 104
• 5b Koe BK, Zechmeister L. Arch. Biochem. Biophys. 1952; 41: 236
• 6 Meléndez-Martínez AJ, Britton G, Vicario IM, Heredia FJ. Food Chem. 2007; 101: 1145
• 7a Zechmeister L, Sandoval A. J. Am. Chem. Soc. 1946; 68: 197
• 7b Wallace V, Porter JW. Arch. Biochem. Biophys. 1952; 36: 468
• 8 Meléndez-Martínez AJ, Mapelli-Brahm P, Benítez-González A, Stinco CM. Arch. Biochem. Biophys. 2015; 572: 188
• 9 Meléndez-Martínez AJ, Stinco CM, Mapelli-Brahm P. Nutrients 2019; 11: 1093
• 10a Clough JM, Pattenden G. J. Chem. Soc., Chem. Commun. 1979; 616
• 10b Meléndez-Martínez AJ, Paulino M, Stinco CM, Mapelli-Brahm P, Wang X.-D. J. Agric. Food Chem. 2014; 62: 12399
• 11 Clough JM, Pattenden G. Tetrahedron Lett. 1979; 20: 5043
• 12a Davis JB, Jackman LM, Siddons PT, Weedon BC. L. J. Chem. Soc. C 1966; 2154
• 12b Ernst H, Henrich K. DE Patent 10349983, 2005
• 13a Bouzbouz S, Kirschleger B. Synlett 1994; 763
• 13b Eis K, Schmalz H.-G. Synthesis 1997; 202
• 14 Kuk J, Kim BS, Jung H, Choi S, Park J.-Y, Koo S. J. Org. Chem. 2008; 73: 1991
• 15 Babler J, Coghlan MJ, Feng M, Fries P. J. Org. Chem. 1979; 44: 1716
• 16 Giam CS, Kikukawa K, Trujillo DA. Org. Prep. Proced. Int. 1981; 13: 137
• 17a Choi H, Ji M, Park M, Yun I.-K, Oh S.-S, Baik W, Koo S. J. Org. Chem. 1999; 64: 8051
• 17b Ji M, Choi H, Park M, Kee M, Jeong YC, Koo S. Angew. Chem. Int. Ed. 2001; 40: 3627
• 17c Ji M, Choi H, Jeong YC, Jin J, Baik W, Lee S, Kim JS, Park M, Koo S. Helv. Chim. Acta 2003; 86: 2620
• 17d Guha SK, Koo S. J. Org. Chem. 2005; 70: 9662
• 17e Choi E, Yeo JE, Koo S. Adv. Synth. Catal. 2008; 350: 365
• 17f Oh E.-T, Kim Y.-H, Jin J, Su L, Seo J.-A, Koo S. J. Org. Chem. 2014; 79: 4712
• 17g Kim M, Jung H, Aragonès AC, Díez-Pérez I, Ahn K.-H, Chung W.-J, Kim D, Koo S. Org. Lett. 2018; 20: 493
• 17h Lim B, Kim Y.-H, Kim H, Park M, Yeo H, Koo S. Bull. Korean Chem. Soc. 2022; 43: 1037
• 18 Martínez A, Stinco CM, Meléndez-Martínez AJ. J. Phys. Chem. B 2014; 118: 9819
• 19 Koe BK, Zechmeister L. Arch. Biochem. Biophys. 1953; 46: 100
• 20 Clough JM, Pattenden G. J. Chem. Soc., Perkin Trans. 1 1983; 3011