Synthesis of ω-Methylsulfinyl- and ω-Methylsulfonylalkyl Glucosinolates

Abstract

General pathways were devised to synthesize ω-methylsulfinyl- and ω-methylsulfonylalkyl glucosinolates, which represent an important class of structurally homogeneous plant specialized metabolites. The first approach was based on the selective S-oxidation of ω-methylsulfanyl analogs previously obtained in our laboratory, producing the corresponding sulfoxide or sulfone counterparts in moderate yields. In an alternative approach, previously prepared ω-nitroalkyl methylsulfide precursors were selectively oxidized either to sulfoxides or to sulfones. The key-thiofunctionalized hydroximoyl chloride intermediates were prepared in situ from sulfoxides or sulfones using a nitronate chlorination strategy. A coupling reaction with 1-thio-β-d-glucopyranose was directly applied, followed by O-sulfation of the intermediate thiohydroximates. The final deprotection of the sugar moiety produced the target compounds, including renowned glucoraphanin and homologs, intended for further bioactivity investigations.

Keywords: glucosinolates; sulfones; sulfoxides; thiohydroximates.

Figure 1

Glucosinolate (GSL) general structure 1 and their myrosinase-catalyzed hydrolysis to isothiocyanates (ITCs).

Figure 2

The general structure of glucosinolates (GSLs) bearing a ω-thiofunctionalized alkyl chain. Legend used for GSLs mentioned in this study: 2a–g, ω-methylsulfanyl-; 3a–g, ω-methylsulfinyl-; 4a–g, ω-methylsulfonylalkyl GSL.

Scheme 1

Pathway 1—oxidation of ω-methylsulfanylalkyl thiohydroximate precursors 5a–g [29] to yield protected glucosyl ω-methylsulfinyl and ω-methylsulfonylalkyl counterparts 6a–g and 7a–g, using the periodate and oxone processes, respectively.

Scheme 2

General conversion of thiohydroximates 6a–g and 7a–g into per-O-acetylated glucosinolates (GSLs) 8a–g and 9a–g and final deprotection of the glucopyranosyl moiety to produce GSLs 3a–g and 4a–g.

Figure 3

Methods to generate nitrile oxides.

Scheme 3

Pathway 2a—oxidation of sulfide precursors 10a–g [29] to sulfoxides 11a–g or sulfones 12a–g.

Scheme 4

Pathway 2b—synthetic sequence involving in situ generation of intermediate nitrile oxides from hydroximoyl chlorides 13a–g or 14a–g, followed by peracetylated 1-thio-glucopyranose coupling to deliver glycosyl thiohydroximates 6a–g and 7a–g.