A New and Effective Approach to the Synthesis of Sulforaphane

Title:A New and Effective Approach to the Synthesis of Sulforaphane

Volume: 13 Issue: 1

Author(s): Duy-Viet Vo, Van-Dat Truong, Thanh-Dao Tran, Van-Thanh-Nhan Do, Ngoc-Tuan-Anh Pham and Khac-Minh Thai

Affiliation:

Keywords: Brassicaceae, cancer prevention, isothiocyanate, sulforaphane, thiolane, thiolanium salt.

Abstract: Background: Sulforaphane [1-isothiocyanato-(4-methylsulfinyl)butane] identified from Brassicaceae appears to possess health benefits such as activities against breast, skin and prostate cancer and diabetes. in vitro and in vivo studies provide evidence that it can provide protection at every stage of cancer progression. Sulforaphane was firstly synthesized by Von Schmidt and P.Karrer in 1948 via phthalimide route but after Zhang and co-worker reported its bioactivity in 1992, the chemical synthesis of sulforaphane by alternate route has attracted several research groups in the past 20 years .

Methods: The synthesis started with the preparation of -methylthiolanium tetrafluoroborate by sonication of thiolane (1) with methyl iodide followed by anionic metathesis with NaBF4 in -butanol to give thiolanium tetrafluorborate (2). The ring opening of 2 by S_N2 is conducted in 16 hours at 60 °C (as indicated by TLC) to obtain 1-azido-(4- methylsulfinyl)butane (3). Conversion 3 into Erucin (4) was successfully obtained by Staudinger reaction, followed by oxidation of 4 in transition metal-free condition (H₂O₂/ glacial acetic acid) to give sulforaphane in racemic form.

Results: Sulforaphane was obtained with 41% yield overall via only four steps with high purity without column chromatography. The approach not only opened up a new synthetic pathway to this naturally occurring isothiocyanate and its analogues, but also suggested a possible solution for converting by-products in petroleum refining processes into useful compounds.

Conclusion: Sulforaphane was successfully synthesized from thiolane, a waste product in petroleum processing in a simpler and more efficient fashion, eco-friendy approach. All products were obtained in high yield and high purity. In comparison with previously reported strategies, this new approach is believed to be the shortest and the most efficient synthetic route to date.

Cite this article as:

Vo Duy-Viet, Truong Van-Dat, Tran Thanh-Dao, Do Van-Thanh-Nhan, Pham Ngoc-Tuan-Anh and Thai Khac-Minh, A New and Effective Approach to the Synthesis of Sulforaphane, Letters in Organic Chemistry 2016; 13 (1) . https://dx.doi.org/10.2174/1570178611666151015214407