Structure and total synthesis of benzylthiocrellidone, a novel dimedone-based vinyl sulfide from the sponge Crella spinulata

Abstract

A concise synthesis of the yellow pigment benzylthiocrellidone 1, based on a Michael addition–elimination of dimedone 2 to the ketene thioacetal 7 derived from dimedone, benzyl bromide and carbon disulfide, is described. The synthetic pigment had an X-ray crystal structure identical to that measured for the natural product.

References

1. W. M. Bandaranayake and W. A. Wickramasinghe, Australian Institute of Marine Science Report, 1995, No. 23 (27 pp.).
2. For the dimedone–formaldehyde reaction see: (a) E. C. Horning and M. G. Horning, J. Org. Chem., 1946, 11, 95For an example of a naturally occurring prenylated cyclohexane-1,3-dione see: (b) H. Obara, J. Onodera, Y. Machida and S. Yada, Bull. Chem. Soc. Jpn., 1989, 62, 3034; (c) M. R. Cann, A. Davis and P. V. R. Shannon, J. Chem. Soc., Perkin Trans. 1., 1982, 375.
3. B. D. Akehurst and J. R. Bartels-Keith, J. Chem. Soc., 1957, 4798.
4. K. Fuchs and L. A. Paquette, J. Org. Chem., 1994, 59, 528.
5. (a) A. Z.-Q. Khan and J. Sandström, J. Chem. Soc., Perkin Trans. 1., 1988, 2085; (b) D. Villemin and A. B. Alloum, Synthesis, 1991, 301 We produced 7 from dimedone using the literature procedure in an unoptimised 20% yield.
6. Synthetic benzylthiocrellidone was prepared from dimedone and the ketene dithioacetal 7 as follows: potassium tert-butoxide (42 mg, 0.36 mmol) was added in one portion to a solution of dimedone (51 mg, 0.36 mmol) in THF (5 ml) and the mixture was then stirred at room temperature for 30 min. A solution of the ketene dithioacetal 7(140 mg, 0.35 mmol) in THF (2 ml) was added dropwise over 10 min and the mixture was then left to stir overnight. Ether (10 ml) was added, and the mixture was extracted with water (2 × 10 ml). The combined aqueous extracts were acidified with 1 M HCl and the precipitated yellow solid was collected by filtration. Recrystallisation from methanol gave benzylthiocrellidone(87 mg, 60%) as yellow crystals, mp 202–204 °C; v_max(Nujol^®)/cm^–1 2921, 2853, 1687, 1640, 1604, 1461, 1375, 1328; δ_H(360 MHz, CDCl₃), 1.13 (12H, s, 4 × Me), 2.47 (8H, s, 4 ×CH₂), 3.81 (2H, s, SCH₂Ph), 7.25–7.34 (5H, m, C₆H₅); δ_c(90 MHz, d₆-DMSO), 28.4 (q), 39.0 (t), 127.7 (d), 128.9 (d), 129.5 (d), 136.6 (s), 171.8 (s)(some peaks not evident due to tautomeric exchange); m/z(Electrospray) 413.1754, C₂₄H₂₉O₄S (MH⁺) requires 413.1787.
7. The X-ray structure for synthetic benzylthiocrellidone, shown in Fig. 1, was identical to the X-ray crystal structure measured for the natural product isolated from Crella spinulata.¹ A crystal of 1 was encapsulated in a film of RS3000 perfluoropolyether oil and mounted on a glass fibre before transfer to the diffractometer; Crystal data. C₂₄H₂₈O₄S, M= 412.52, monoclinic, a= 5.939(4), b= 14.950(7), c= 11.748(7)Å, β= 91.14(6)°, U= 1042.9(11)ų, T= 150(2) K, space group P2₁(No. 4), Z= 2, D_c= 1.314 g cm^–3, µ(Mo-Kα)= 0.183 mm^–1, 3195 unique reflections measured and used in all calculations. Final R₁[2171 F≥ 4σ(F)]= 0.0988 and wR(all F²) was 0.244. CCDC reference number 207/312. See http://www.rsc.org/suppdata/p1/1999/847 for crystallographic files in .cif format.