Synthesis of a Ceramide Sphingolipid as a Potential Sex Pheromone of the Hair Crab Erimacrus isenbeckii Using Butane-2,3-diacetal Desymmetrised Glycolic Acid Building Blocks

Abstract

A stereoselective synthesis of a ceramide sphingolipid as a potential sex pheromone of the hair crab Erimacrus isenbeckii is reported using diastereoselective alkylation and aldol reactions of butane-2,3-diacetal (BDA) desymmetrised glycolic acid building blocks as the key synthetic steps.

Key words

acetals - chiral auxiliaries - pheromones - sphingolipids - stereoselective synthesis

References

• 3 Asai N. Fusetani N. Matsunaga S. Sasaki J. Tetrahedron  2000,  56:  9895 
• 4 Loukaci A. Bultel-Ponce V. Longeon A. Guyot M. J. Nat. Prod.  2000,  63:  799 
• 5 Morita M. Motoki K. Akimoto K. Natori T. Sakai T. Sawa E. Yamaji K. Koezuka Y. Kobayashi E. Fukushima H. J. Med. Chem.  1995,  38:  2176 
• 6 Asai N. Fusetani N. Matsunaga S. J. Nat. Prod.  2001,  64:  1210 
• 7 Masuda Y. Yoshida M. Mori K. Biosci., Biotechnol., Biochem.  2002,  66:  1531 
• 8a Diez E. Dixon DJ. Ley SV. Angew. Chem. Int. Ed.  2001,  40:  2906 
• 8b Dixon DJ. Ley SV. Polara A. Sheppard T. Org. Lett.  2001,  3:  3749 
• 8c Dixon DJ. Ley SV. Rodriguez F. Angew. Chem. Int. Ed.  2001,  40:  4763 
• 8d Dixon DJ. Ley SV. Rodriguez F. Org. Lett.  2001,  3:  3753 
• 8e Dixon DJ. Guarna A. Ley SV. Polara A. Rodriguez F. Synthesis  2002,  1973 
• 8f Ley SV. Diez E. Dixon DJ. Guy RT. Michel P. Nattrass GL. Sheppard TD. Org. Biomol. Chem.  2004,  2:  3608 
• 8g Ley SV. Dixon DJ. Guy RT. Palomero MA. Polara A. Rodriguez F. Sheppard TD. Org. Biomol. Chem.  2004,  2:  3618 
• 8h Michel P. Ley SV. Synthesis  2003,  1598 
• 9a Diez E. Dixon DJ. Ley SV. Polara A. Rodriguez F. Synlett  2003,  1186 
• 9b Diez E. Dixon DJ. Ley SV. Polara A. Rodriguez F. Helv. Chim. Acta  2003,  86:  3717 
• 10 Laib T. Chastanet J. Zhu JP. J. Org. Chem.  1998,  63:  1709 
• 11 Sandri J. Viala J. Synth. Commun.  1992,  22:  2945 
• 12 Soai K. Ookawa A. J. Org. Chem.  1986,  51:  4000 
• 14 Koskinen AMP. Chen JS. Tetrahedron Lett.  1991,  32:  6977 
• 15 Masaki Y. Yoshizawa K. Itoh A. Tetrahedron Lett.  1996,  37:  9321 
• 16 Okazoe T. Takai K. Utimoto K. J. Am. Chem. Soc.  1987,  109:  951 
• 17 Pross A. Sternhell S. Aust. J. Chem.  1970,  23:  989 

1

New address: D. J. Dixon, Department of Chemistry, University of Manchester, Oxford Road, Manchester, M13 9PL, UK.

2

New address: T. D. Sheppard, Chemistry Department, University College London, Chirstopher Ingold Laboratories, 20 Gordon Street, London, WC1H 0AJ, UK.

13

The X-ray structural data for this compound have been deposited with the Cambridge Crystallographic Data Centre, reference number CCDC 257805. These data can be obtained free of charge on the web at www.ccdc.cam.ac.uk/data_request/cif, or by emailing [e-mail], or by contacting The Cambridge Crystallographic Data Centre, 12, Union Road, Cambridge CB2 1EZ, UK; fax: [phone].

18

Physical data for pheromone 1, (2S,2′R,3S,4S)-2-(2′-hydroxy-21′-methyl-docosanoylamino)-1,3,4-pentadecanetriol: [α]_D ²² +12.5 (c 0.16, CHCl₃-MeOH, 1:1) {lit. [α]_D ²⁸ +14 (c 0.70, CHCl₃-MeOH, 1:1), see ref. [7] ]. IR (film): ν_max = 3377 (O-H, N-H), 2917 (C-H), 2850 (C-H), 2480, 1639 (C=O), 1620, 1471, 1049 (C-O) cm^-1. ¹H NMR (600 MHz, CDCl₃-CD₃OD, 1:1): δ = 0.82 [6 H, d, J = 6.6 Hz, CH(CH ₃ )₂], 0.85 (3 H, t, J = 6.6 Hz, CH₃), 1.06-1.60 [55 H, br m, 27 × CH₂, CH(CH₃)₂], 1.60-1.69 (1 H, m, H-5), 1.70-1.80 (1 H, m, H-5), 3.50-3.53 (2 H, m, H-4, H-2′), 3.71 (1 H, dd, J = 11.3, 4.8 Hz, H-1), 3.76 (1 H, dd, J = 11.3, 4.8 Hz, H-1), 4.00 (1 H, dd, J = 7.7, 3.7 Hz, H-3), 4.06-4.10 (1 H, m, H-2). ¹³C NMR (125 MHz, CDCl₃-CD₃OD, 1:1): δ = 13.10, 21.70, 22.00, 24.50, 25.20, 26.80, 27.30, 28.70, 28.88, 28.93, 29.01, 29.03, 29.10, 29.12, 29.30, 31.30, 31.90, 33.90, 38.40, 50.90, 60.30, 71.20, 71.60, 74.60, 175.17. Found (ES): [M - Na]⁺ 650.5729, C₃₈H₇₇NO₅ requires 650.5694.