Total Synthesis of the Phytotoxic Agent Herbarumin II Using Butane Diacetals of Glycolic Acid as Building Blocks

Abstract

The total synthesis of the phytotoxic agent herbarumin II has provided an ideal stage to exploit the utility of butane diacetal (BDA) desymmetrised glycolic acid as a primary building block.

acetals - aldol - alkylation - asymmetric synthesis - natural products - metathesis

References

1 Rivero-Cruz JF. Garcia-Aguirre G. Cerda-Garcia-Rojas CM. Mata R. Tetrahedron  2000,  56:  5337 

2a Evidente A. Lanzetta R. Capasso R. Vurro M. Bottalico A. Phytochemistry  1993,  34:  999 

2b de Napoli L. Messere A. Palomba D. Piccialli V. Evidente A. Piccialli G. J. Org. Chem.  2000,  65:  3432 

3 Arone A. Assante M. Nasini G. Ragg E. Gazz. Chim. Ital.  1993,  123:  71 

For previous synthesis of herbarumin I and II:

4a Fürstner A. Radkowski K. Chem. Commun.  2001,  671 

4b Fürstner A. Radkowski K. Wirtz C. Goddard R. Lehmann CW. Mynott R. J. Am. Chem. Soc.  2002,  124:  7061 

4c Sabino AA. Pilli R. Tetrahedron Lett.  2002,  43:  2819 

5a Baeschlin DK. Dixon DJ. Foster AC. Ince SJ. Ley SV. Priepke HWM. Reynolds DJ. Chem. Rev.  2001,  101:  53 

5b Diez E. Dixon DJ. Ley SV. Angew. Chem. Int. Ed.  2001,  40:  2906 

5c Dixon DJ. Ley SV. Polara A. Sheppard TS. Org. Lett.  2001,  3:  3749 

5d Dixon DJ. Ley SV. Rodriguez F. Org. Lett.  2001,  3:  3753 

5e Dixon DJ. Ley SV. Rodriguez F. Angew. Chem. Int. Ed.  2001,  40:  4763 

5f Ley SV. Michel P. Synlett  2001,  1793 

5g Michel P. Ley SV. Angew. Chem. Int. Ed.  2002,  41:  3898 

5h Dixon DJ. Guarna A. Ley SV. Polara A. Rodriguez F. Synthesis  2002,  1973 

6

Data for (R,R): [α]_D ²⁵ -211.5 (c 0.4, CHCl₃); mp 40-41 °C in agreement with the following reference: Michel, P.; Ley, S. V. Synthesis 2003, in press.

7

Data for (S,S): [α]_D ²⁵ +208.3 (c 1.2, CHCl₃); mp 41-42 °C in agreement with the following reference: Michel, P.; Ley, S. V. Synthesis 2003, in press.

8

Minor diastereomer was not detected by ¹H NMR.

9a Othani I. Kusumi T. Kashman K. Kakisawa H. J. Am. Chem. Soc.  1991,  113:  4092 

9b Kouda K. Ooi T. Kusumi T. Tetrahedron. Lett.  1999,  40:  3005 

10 Inanaga J. Hirata K. Saeki H. Katsuki T. Yamaguchi M. Bull. Chem. Soc. Jpn.  1979,  52:  1989 

11 Calculated from Macromodel’s version of MM2 forcefield, see: Mohamadi F. Richards NGJ. Guida WC. Liskamp R. Lipton M. Caufield C. Chang G. Hendrickson T. Still WCJ. Comp. Chem.  1990,  11:  440 

12a Nguyen ST. Grubbs RH. Ziller JW. J. Am. Chem. Soc.  1993,  115:  9858 

12b Schwab P. France MB. Ziller JW. Grubbs RH. Angew. Chem. Int. Ed. Engl.  1995,  34:  2039 

12c Schwab P. Grubbs RH. Ziller JW. J. Am. Chem. Soc.  1996,  118:  100 

13a Scholl M. Trnka TM. Morgan JP. Grubbs RH. Tetrahedron Lett.  1999,  40:  2247 

13b Scholl M. Ding S. Lee CW. Grubbs RH. Org. Lett.  1999,  1:  953 

14 Fürstner A. Guth O. Duffels A. Seidel G. Liebl M. Gabor B. Mynott R. Chem.-Eur. J.  2001,  7:  4811 

15

Data for herbarumin II: δ_H (600 MHz, MeOH-d ₄) 5.57 (1 H, ddd, J = 15.6 Hz, 2.0 Hz, 1.0 Hz, CH=CH), 5.51 (1 H, dddd, J = 15.6 Hz, 9.9 Hz, 4.1 Hz, 2.0 Hz, CH=CH), 5.17 (1 H, td, J = 9.3 Hz, 2.6 Hz, CHOCO), 4.34 (1 H, quint, J = 1.9 Hz, CHOH), 3.85 (1 H, dd, J = 10.5 Hz, 2.9 Hz, CHOHCH₂), 3.52 (1 H, dd, J = 9.6 Hz, 2.3 Hz, CHOH), 2.28 (1 H, m, CH=CHCH _aH_b), 2.08 (1 H, m, CH_a H _b), 1.87 (1 H, m, CH_aH_bCH _cH_d) 1.80 (1 H, m, CHCH _eH_f), 1.76 (1 H, m, CH_c H _d), 1.55 (1 H, m, CH_e H _f), 1.44 (1 H, m, CH _gH_hCH₃), 1.34 (1 H, m, CH_g H _h), 0.93 (3 H, t, J = 7.4 Hz, CH₃); δ_C (100 MHz, MeOH-d ₄) 177.7 (C=O), 134.5 (CH), 123.9 (CH), 74.5 (CH), 74.3 (CH), 74.0 (CH), 72.3 (CH), 35.6 (CH₂), 35.4 (CH₂), 30.1 (CH₂), 19.1 (CH₂), 14.8 (CH₃).