Short Total Synthesis of Ajoene, (E,Z)-4,5,9-Trithiadodeca-1,6,11-triene 9-oxide, in Batch and (E,Z)-4,5,9-Trithiadodeca-1,7,11-triene in Continuous Flow

Marina Yamamoto Raynbird; Filipa Silva; Harry Smallman; Shaista S Khokhar; Daniel Neef; Gareth J S Evans; Thomas Wirth

doi:10.1002/chem.202001598

Short Total Synthesis of Ajoene, (E,Z)-4,5,9-Trithiadodeca-1,6,11-triene 9-oxide, in Batch and (E,Z)-4,5,9-Trithiadodeca-1,7,11-triene in Continuous Flow

Chemistry. 2020 Jul 8;26(38):8363-8367. doi: 10.1002/chem.202001598. Epub 2020 Jun 15.

Authors

Marina Yamamoto Raynbird¹, Filipa Silva¹, Harry Smallman¹, Shaista S Khokhar², Daniel Neef², Gareth J S Evans², Thomas Wirth¹

Affiliations

¹ School of Chemistry, Cardiff University, Park Place, Main Building, Cardiff, CF10 3AT, UK.
² Neem Biotech, Roseheyworth Business Park North, Abertillery, NP13 1SX, UK.

Abstract

A short total synthesis of ajoene, (E,Z)-4,5,9-trithiadodeca-1,6,11-triene 9-oxide, has been achieved over six steps. In addition, a continuous flow synthesis under mild reaction conditions to (E,Z)-4,5,9-trithiadodeca-1,7,11-triene is described starting from simple and easily accessible starting materials. Over four steps including propargylation, radical addition of thioacetate, deprotection, and disulfide formation/ allylation, the target product can be obtained at a rate of 0.26 g h^-1 in an overall yield of 12 %.

Keywords: ajoene; disulfides; flow chemistry; garlic; organosulfur compounds.

Grants and funding

KESS