Synthesis of Ieodomycin D

Abstract

A synthesis of the marine natural product ieodomycin D has been achieved in seven steps and 16% overall yield from commercially available pyridinium-1-sulfonate. The key synthetic step was a B-alkyl Suzuki–Miyaura cross-coupling reaction. The enantiomer of ieodomycin D was also prepared using the same synthetic strategy.

Key words

ieodomycin D - B-alkyl Suzuki–Miyaura reaction - marine natural product - antibacterial effects - 5-bromopenta-2,4-dienal

• References and Notes

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• 13 Experimental Procedure and Analytical Data for Ieodomycin D (4) The methylester 12 (1.0 equiv) was dissolved in a mixture of THF (50 mL/mmol 12), MeOH (50 mL/mmol 12) and water (25 mL/mmol 12), cooled in an ice bath and added solid LiOH (30 equiv). The ice bath was then removed, and the mixture was stirred for 6 h. MeOH and THF were removed in vacuo, and to the residue was added sat. aq NaH₂PO₄ and extracted with EtOAc (3×). The combined organic layers were dried over Na₂SO₄ and evaporated in vacuo to give the desired product as a colorless oil (96% yield, 20 mg) which solidified in the freezer. [α]_D ²⁰ –5 (c 1.3, CHCl₃). ¹H NMR (400 MHz, CD₃OD); δ = 7.25 (dd, J = 15.3, 10.3 Hz, 1 H), 6.32–6.12 (m, 2 H), 5.78 (d, J = 15.4 Hz, 1 H), 3.81–3.66 (m, 1 H), 2.24–2.16 (m, 2 H), 1.63–1.36 (m, 4 H), 1.15 (d, J = 6.2 Hz, 3 H). ¹³C NMR (101 MHz, CD₃OD): δ = 170.8, 146.9, 145.7, 129.8, 120.5, 68.3, 39.6, 33.9, 26.1, 23.5. HRMS (EI): m/z calcd for C₁₀H₁₆O₃ [M]⁺: 184.1099; found: 184,1091.
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