Organic Reactions in Water: Optimization of the Synthesis of (±)-Manzamenone A Using Surfactant Catalysts

Abstract

Improved procedures exploiting surfactant catalysts have been developed for the conversion of (±)-untenone A to (±)-manzamenone A in an aqueous medium. The consequent availability of (±)-manzamenone A has allowed the synthesis of a biologically interesting cyclopropyl analogue of the natural product.

catalysis - cycloaddition - natural product - total synthesis

References

1 Tsukamoto S. Takeuchi S. Ishibashi M. Kobayashi J. J. Org. Chem.  1992,  57:  5255 

2 Kobayashi J. Tsukamoto S. Takeuchi S. Ishibashi M. Tetrahedron  1993,  49:  5955 

3 Takeuchi S. Kikuchi T. Tsukamoto S. Ishibashi M. Kobayashi J. Tetrahedron  1995,  51:  5979 

4 Al-Busafi S. Drew MGB. Sanders T. Whitehead RC. Tetrahedron Lett.  1998,  39:  1647 

5 Ishibashi M. Takeuchi S. Kobayashi J. Tetrahedron Lett.  1993,  34:  3749 

6 Al-Busafi S. Whitehead RC. Tetrahedron Lett.  2000,  41:  3467 

7 Al-Busafi S. Doncaster JR. Drew MGB. Regan AC. Whitehead RC. J. Chem. Soc., Perkin Trans. 1  2002,  476 

8

Cyclopropyl compounds of type 4 were of interest as potential alkylating agents of DNA and therefore as candidates for anti-cancer screening.

9a Li C.-J. Chan T.-H. Organic Reactions in Aqueous Media   John Wiley and Sons; New York: 1997. 

9b Organic Synthesis in Water   Grieco PA. Blacky Academic and Professional; London: 1998. 

10 Tascioglu S. Tetrahedron  1996,  52:  11113 

11 Lee KH. de Mayo P. Photochem. Photobiol.  1980,  31:  311 

12 Nakamura Y. J. Chem. Soc., Chem. Commun.  1988,  477 

13

Representative Procedure for the Preparation of 1a from 2 Using SDS:
A mixture of H₂O (13 mL) and SDS (0.65 g) was stirred at 25 °C for 5 min when untenone A (2) (50 mg, 0.13 mmol) was added. The reaction mixture was stirred rapidly for 6 h at 25 °C when it was extracted with EtOAc (3 ¥ 20 mL). The combined organic extracts were washed with brine (20 mL), H₂O (20 mL), dried (MgSO₄) and concentrated in vacuo to give a solid. This solid was taken up in the minimum volume of EtOAc (ca. 5 mL) and filtered in order to remove any remaining SDS. The filtrate was concentrated in vacuo to give a crude product, which was purified by flash column chromatography [SiO₂; gradient elution: EtOAc:petroleum ether (40:60), 1:5, to neat EtOAc] to give manzamenone A (36 mg, 75%) with spectroscopic data identical to those reported previously.

For BASC catalysts see the following references:

14a Manabe K. Mori Y. Kobayashi S. Synlett  1999,  1401 

14b Manabe K. Kobayashi S. Org. Lett.  1999,  1:  1965 

14c Manabe K. Mori Y. Kobayashi S. Tetrahedron  2001,  57:  2537 

14d Manabe K. Sun X.-M. Kobayashi S. J. Am. Chem. Soc.  2001,  123:  10101 

For LASC catalysts see the following references:

15a Kobayashi S. Wakabayashi T. Tetrahedron Lett.  1998,  39:  5389 

15b Manabe K. Kobayashi S. Synlett  1999,  547 

15c Manabe K. Mori Y. Wakabayashi T. Nagayama S. Kobayashi S. J. Am. Chem. Soc.  2000,  122:  7202 

16

Representative Procedure for the Preparation of 1a from 2 Using BASC 5
A mixture of water (1 mL) and BASC 5 (4.2 mg, 0.013 mmol) was stirred at 25 °C for 5 min when untenone A(2) (50 mg, 0.13 mmol) was added. The reaction mixture was stirred rapidly for 7.5 h, when brine (5 mL) and a sat. aq solution of NaHCO₃ (5 mL) were added. Organic material was extracted into EtOAc (3 ¥ 7 mL) and the combined organic extracts were dried (MgSO₄) and concentrated in vacuo to give the crude product. Purification by flash column chromatography [SiO₂; gradient elution: EtOAc-petroleum ether (40:60), 1:5, to neat EtOAc] gave manzamenone A (33 mg, 69%) with spectroscopic data identical to those reported previously.

17

Representative Procedure for the Preparation of 1a from 2 Using LASC 6
A similar procedure to that used for BASC 5 [H₂O (3 mL); LASC 6 (11mg, 0.013 mmol); untenone A (50 mg, 0.13 mmol); reaction time, 1 h] gave manzamenone A (35 mg, 73%) after purification by flash column chromatography.

18 Hashimoto N. Aoyama T. Shioiri T. Chem. Pharm. Bull.  1981,  29:  1475 

19 Golobolov YG. Nesmeyanov AN. Lysenko VP. Boldeskul IE. Tetrahedron  1987,  43:  2609 

20 For a cautionary note on the use of diazomethane see: Moore JA. Reed DE. Org. Synth., Coll. Vol. V   John Wiley and Sons; New York: 1973.  p.351-355  

21

Data for compound 11: Colourless solid, mp 62-64 °C. IR(film): 1762 (C=O), 1741 (C=O), 1722 (C=O) cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 0.90 [6 H, br t, J = 6.8 Hz, C(26)H₃ and C(42)H₃], 1.20-1.60 [58 H, m, C(12)H₂ to C(25)H₂ and C(27)H₂ to C(41)H₂], 1.62 [1 H, d, J = 5.3 Hz, one of C(9)H₂], 1.84 [1 H, d, J = 5.3 Hz, one of C(9)H₂], 2.14 [2 H, br t, J = 7.5 Hz, C(11)H₂], 2.55 [1 H, dd, J = 9.3, 4.8 Hz, C(1)H], 3.11 [1 H, dd, J = 9.3, 5.4 Hz, C(6)H], 3.28 [1 H, d, J = 4.8 Hz, C(2)H], 3.53 [1 H, br, C(5)H], 3.58 (3 H, s, CO₂CH₃), 3.77 (6 H, s, 2 ¥ CO₂CH₃), 5.70 [1 H, d, J = 1.1 Hz, C(4)H]. ¹³C NMR (75.4 MHz, CDCl₃): δ = 14.39 [C(26)H₃ and C(42)H₃], 22.96, 27.31, 27.98, 28.17, 29.45, 29.64, 29.81, 29.87, 29.90, 29.94, 29.99, 32.20 [C(12)H₂ to C(25)H₂ and C(27)H₂ to C(41)H₂, many overlapping], 36.71 [C(11)H₂], 38.80 [C(1)H], 41.62 [C(5)H], 42.49 [C(6)H], 44.01 [C(2)H], 44.93, 45.25 [C(8) and C(10)], 52.36, 52.59 and 52.88 (3 ¥ CO₂CH₃), 122.78 [C(4)H], 138.23 [C(3)], 168.31, 171.52, 174.65 [C(43), C(44) and C(45)], 205.84 [C(7)]. MS (APCI⁺): m/z (%) = 772 (65) [MH⁺], 771 (100). (Found: 771.6135. C₄₈H₈₃O₇ requires 771.6139).