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.

Key words

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

References

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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.

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).