Formal total synthesis of (-)-hamigeran B from a chemo-enzymatically prepared building block with quaternary chiral center

Kazuaki Kuwata, Rie Fujita, Kengo Hanaya, Shuhei Higashibayashi, Takeshi Sugai

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2 Citations (Scopus)

Abstract

A formal total synthesis of (-)-hamigeran B was achieved in 17 steps from commercially available ethyl 2-oxocyclopentanecarboxylate. Carbonyl reductase-catalyzed asymmetric reduction and the subsequent chemical transformations furnished an enantiomerically pure synthetic intermediate, (R)-5-formyl-2-isopropyl-5-methylcyclopent-1-en-1-yl trifluoromethylsulfonate. Suzuki-Miyaura coupling with Gao's arylboronate [2-(2-formyl-3-methoxy-5-methylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane], under PdCl2(dppf)•CH2Cl2 catalysis, and the subsequent cyclization by way of intramolecular reductive SmI2-mediated 1,2-diol formation provided a tricyclic skeleton with a tetrasubstituted double bond between C-1 and C-9b. Upon hydrogenation of this double bond, the proper stereochemistry of the remaining chiral centers was established. Exclusive addition of the hydrogen atom from the β-face occurred, owing to the shielding of the α-face with a bulky TBS protective group on the C-4 alcohol. The hydrogenation products were transformed into Clive's synthetic precursor for (-)-hamigeran B.

Original languageEnglish
JournalTetrahedron
DOIs
Publication statusAccepted/In press - 2018 Jan 1

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Keywords

  • Alkenyl triflate
  • Cyclic terpenoid
  • Hamigeran skeleton
  • Natural product synthesis
  • PdCl2(dppf)
  • Suzuki-Miyaura coupling

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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