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Article

Synthesis of ω-Methylsulfinyl- and ω-Methylsulfonylalkyl Glucosinolates

by
Manolis Mavratzotis
1,
Stéphanie Cassel
1,2,
Gina Rosalinda De Nicola
3,*,
Sabine Montaut
4,* and
Patrick Rollin
1
1
ICOA, CNRS, Université d’Orléans, UMR 7311, BP 6759, F-45067 Orléans, France
2
Laboratoire SOFTMAT, UMR CNRS 5623, Université P. Sabatier Toulouse III, 118 Route de Narbonne, 31062 Toulouse CEDEX 9, France
3
Research Centre for Vegetables and Ornamental Crops, Council for Agricultural Research and Economics (CREA), Via dei Fiori 8, 51017 Pescia, Italy
4
School of Natural Sciences, Laurentian University, 935 Ramsey Lake Road, Sudbury, ON P3E 2C6, Canada
*
Authors to whom correspondence should be addressed.
Molecules 2025, 30(3), 704; https://doi.org/10.3390/molecules30030704
Submission received: 29 December 2024 / Revised: 25 January 2025 / Accepted: 3 February 2025 / Published: 5 February 2025
(This article belongs to the Collection Advances in Glycosciences)
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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.

1. Introduction

Glucosinolates (GSLs) 1 are thiosaccharidic specialized metabolites almost exclusively found in all families of the plant order Brassicales. All of the ca. 140 known GSLs display a remarkable structural homogeneity based on a β-d-glucopyrano unit, bearing an O-sulfated anomeric (Z)-thiohydroximate function connected to an aglycon R, the constitution of which is the sole structural variant, depending on plant species. Associated with the enzyme myrosinase (E.C. 3.2.1.147), GSLs can undergo hydrolytic cleavage of the anomeric C–S bond with d-glucose release. The liberated aglycon ordinarily undergoes a Lossen-type rearrangement to mainly produce isothiocyanates (ITCs) (Figure 1) [1,2,3].
Most strikingly, over a third of the actually registered GSL structures contain a terminal thio-function—namely sulfide (2), sulfoxide (3), or sulfone (4)—attached to their aglycon alkyl chain, as shown in Figure 2 [4,5].
Within the order Brassicales, GSLs bearing a ω-thiofunctionalized alkyl chain are mainly found in Brassicaceae and Capparaceae, albeit also frequently as minor components in the GSL profile of other families. However, their diversified bioactivity potential has long been recognized over a broad range of aglycon chain lengths (Figure 2). To highlight one most bio-relevant example, 4RS-(methylsulfinyl)butyl GSL (glucoraphanin, 3c) [6,7,8], bearing a 4RS-methylsulfinylbutyl aglycon stands as a popular source of bioactive sulforaphane (4RS-(methylsulfinyl)butyl ITC) [9,10,11]. Noteworthy, recent findings are shedding light on the traditionally accepted view that the activity of GSLs is exclusively mediated by their degradation products: ITCs. A powdered extract obtained from broccoli seed indicated 3c as a potential agent effective in preventing obesity and related metabolic disorders in high-fat diet (HFD)-fed mice [6]. In recent work, Lucarini et al. found that 3c releases hydrogen sulfide (H2S) in a cysteine-dependent fashion similar to its ITC sulforaphane, suggesting that 3c may be endowed with biological activity based on its H2S-releasing properties [12]. The investigation of direct bioactivities of intact GLSs, particularly ω-thiofunctionalized GSLs, is steadily increasing. Pure 3c obtained from Tuscan black kale seed, according to an established method [13], reduced neuropathic pain in different animal models [12] and improved behavior in rats that were associated with depressive-like phenotypes [14]. Moreover, 3c supplementation was suggested as a useful strategy for prevention and treatment of sarcopenia [15].
Accessing naturally occurring GSLs from plants through extraction processes is generally not straightforward [16,17]. Vegetable sources, which can be considered optimal for an efficient purification of one specific GSL in a reasonable amount, are in very limited numbers [18,19,20]. In fact, plant materials suitable for this purpose have to meet two important characteristics, namely a profile with a restricted number of GSLs and a high content of the GSL of interest [13,21]. Therefore, the synthetic approach could represent a valid alternative to making GSLs available as attractive substrates for biological studies [22].
Nevertheless, since our pioneering study [23], only scarce synthetic efforts have focused on GSLs bearing an external thio-function in the aglycon part. With the aim of analytical and metabolic studies, Botting et al. synthesized isotopically labeled glucoraphanin 3c [24,25] and 4-(methylsulfanyl)butyl GSL (glucoerucin, 2c) [26]. Some additional synthetic achievements have also been reported [27,28]. In the continuation of our previous work [29], we report here general synthetic pathways intending to deliver ω-methylsulfinyl- and ω-methylsulfonylalkyl GSLs 3a–g and 4a–g (Figure 2) for further bioactivity evaluations.

2. Results and Discussion

2.1. Synthetic Pathway 1

Based on our previous investigations of GSL oxidation [30], a first option could be envisaged to access GSL sulfoxides and GSL sulfones. This would implement a strategy of controlled oxidation of the protected glucosyl ω-methylsulfanyl intermediates 5, previously synthesized in our laboratory, to obtain GSL sulfides 2 [29] (Scheme 1).
We were aware of the randomness of this process by relying on preliminary oxidation tests applied to model thiohydroximates, which confirmed the appreciable sensitivity of the anomeric sulfur in oxidative media. In this way, the C1-S bond is cleaved, resulting in glucose expulsion. However, when applying carefully controlled conditions in both periodate and oxone processes, we were pleased to observe a satisfactory outcome. Thus, our sulfide precursors 5a–g could be smoothly converted into the corresponding sulfoxides 6a–g in 42 to 68% yields by the periodate process. A similar conversion could be carried out with oxone, producing the corresponding sulfones 7a–g in yields ranging from 49 to 70%. It is noteworthy that in both reactions, the highest yields were obtained for the thiohydroximates bearing the longest aglycon chains (Table 1). The overall assessment for the conversion of the sulfide precursors 5 was a yield range of 13 to 36% for ω-methylsulfinyl thiohydroximates 6 and 16 to 39% for ω-methylsulfonyl thiohydroximates 7, depending on the length of the aglycon chain, as summarized in Table 1.
The final conversion of the thiohydroximates 6a–g or 7a–g into the target ω-methylsulfinyl GSLs 3a–g or ω-methylsulfonyl GSLs 4a–g was performed according to a previously described protocol [29]. O-sulfation of the hydroximino moiety using sulfur trioxide pyridine complex (PyrSO3), followed by quenching with aqueous potassium hydrogen carbonate, produced the per-O-acetylated GSLs 8a–g (yield range 54–78%) and 9a–g (yield range 56–85%). The carbohydrate moiety was finally deprotected by base-catalyzed methanolysis to produce the corresponding GSLs 3a–g (yield range 80–93%) and 4 (yield range 80–95%) (Scheme 2).

2.2. Synthetic Pathway 2

Having developed in previous work [29] straightforward synthetic processes for the preparation of ω-methylsulfanylnitroalkanes, it was decided to build up an alternative approach to the target thiofunctionalized GSLs 3 and 4. Most synthetic methods developed for GSLs over the years involve as a key step the Z-stereospecific formation of a thiohydroximate function, usually resulting from the 1,3-addition of a glucosyl mercaptan onto a transient nitrile oxide [22]. As they are generally unstable molecular species, nitrile oxides have to be generated in situ through the base-induced conversion of hydroximoyl chlorides, which in turn currently result from the chlorination of aldoximes or nitronates (Figure 3).
Taking advantage of the readily available ω-nitroalkyl methylsulfide precursors 10a–g described in our previous work [29], chemoselective oxidation was applied to obtain sulfoxide homologs 11a–g and sulfone homologs 12a–g, using either sodium periodate or oxone, respectively (Scheme 3).
Following a one-pot nitronate chlorination strategy initially established by Kjaer [31], all nitro-compounds 11a–g or 12a–g were converted into the corresponding hydroximoyl chlorides 13a–g and 14a–g through a two-step process. Nitroalkanes were first treated with sodium sec-butoxide and then chlorinated in chloroform with thionyl chloride at low temperature (−60 °C). The hydroximoyl chlorides were used without further purification by base-catalyzed (NEt3) 1,3-elimination. In situ generated intermediate nitrile oxides 15a–g and 16a–g were used as electrophilic acceptors for coupling with 2,3,4,6-tetra-O-acetyl-1-thio-ω-d-glucopyranose to give the protected thiohydroximate 6a–g and 7a–g [32] (Scheme 4).
This stereospecific addition step produced the corresponding ω-methylsulfinylalkyl- and ω-methylsulfonylalkyl (Z)-thiohydroximates in yields ranging from 30 to 54% for sulfoxides 6a–g and 35 to 55% for sulfones 7a–g (Table 2). Similarly to results obtained along pathway 1, the highest yields were obtained for the thiohydroximates bearing the longest aglycon chains (Table 2). The overall assessment for the conversion of the sulfide precursors 10 was a yield range of 18 to 51% for ω-methylsulfinyl thiohydroximates 6, and 25 to 52% for ω-methylsulfonyl thiohydroximates 7, depending on the length of the aglycon chain, as reported in Table 2.
The final conversion of the thiohydroximates 6a–g or 7a–g into the target ω-methylsulfinyl GSLs 3a–g or ω-methylsulfonyl GSLs 4a–g was performed as reported above, according to Scheme 2 through the NO-sulfation of the glucosyl thiohydroximate, followed by deprotection of the glucopyranosyl moiety.
To sum up, seven ω-methylsulfinyl- and seven ω-methylsulfonylalkyl GSLs were produced and fully characterized. GSLs 3a–g and 4a–g were obtained with an overall yield of 6–25% and 7–31% through pathway 1. Conversely, pathway 2 produced the desired compounds with an overall yield of 13–39% and 16–43%, respectively.

3. Experimental Section

3.1. General Information

All chemicals were purchased from Sigma-Aldrich and used without further purification unless otherwise stated. The details of the general information referring to procedures and instruments used for the purification and full characterization of compounds are the same as those previously reported [29].

3.2. Organic Synthesis

3.2.1. Pathway 1

Selective Oxidation of ω-Sulfides 5 to ω-Sulfoxides 6

Glucosyl thiohydroximates 5a–g were obtained as previously described in [29]. To a stirred solution of the protected glucosyl, thiohydroximate 5 (1 mmol) in methanol (30 mL) cooled at 0 °C and an ice-cold solution of NaIO4 (2 mmol) in water (10 mL) was added dropwise. After stirring at r.t. for 1.5–3 h, the mixture was filtered, and the clear solution was diluted with water (50 mL) and then repeatedly extracted with chloroform (4 × 30 mL). The combined organic phases were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (dichloromethane containing 4–6% v/v methanol) to produce sulfoxides 6a–g as amorphous solids.
  • S-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl) (Z)-3-(methylsulfinyl)propanethiohydroximate (6a).
White amorphous powder (0.21 g, 42% yield), [α]D -16 (c = 0.6, CHCl3). 1H NMR (CDCl3): δ 1.98, 2.01, 2.02, 2.05 (4s, 12H, MeCO), 2.62 (s, 3H, MeSO), 2.85–2.98 (m, 2H, H-8), 3.00–3.14 (m, 2H, H-9), 3.83 (ddd, 1H, J4,5 = 10.2, H-5), 4.11 (dd, 1H, J5,6b = 2.6, J6a,6b = 11.0, H-6b), 4.21 (dd, 1H, J5,6a = 5.1, H-6a), 4.95–5.13 (m, 3H, H-4, H-1, H-2), 5.24 (ft, 1H, J3,4 = 9.0, H-3), 8.54 (bs, 1H, NOH). 13C NMR (CDCl3): δ 20.1, 20.2, 20.3 (MeCO), 24.9 (C-8), 37.7 (MeSO), 50.3 (C-9), 61.6 (C-6), 67.7 (C-4), 69.9 (C2), 73.6 (C-3), 75.3 (C-5), 79.2 (C-1), 147.6 (C=N), 169.6, 169.7, 170.3, 171.0 (C=O). HR-ESI-MS m/z calcd for C18H27NO11S2 497.1026, found 497.1011.
  • S-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl) (Z)-4-(methylsulfinyl)butanethiohydroximate (6b).
White amorphous powder (0.25 g, 49% yield), [α]D -17 (c = 0.9, CHCl3). 1H NMR (CDCl3): δ 1.97, 2.00, 2.02, 2.05 (4s, 12H, MeCO), 2.08–2.19 (m, 2H, H-9), 2.60 (s, 3H, MeSO), 2.67–2.86 (m, 4H, H-8, H-10), 3.83 (ddd, 1H, J4,5 = 10.3, H-5), 4.12 (dd, 1H, J5,6b = 2.6, J6a,6b = 11.1, H-6b), 4.19 (dd, 1H, J5,6a = 5.4, H-6a), 4.96–5.14 (m, 3H, H-4, H-1, H-2), 5.25 (ft, 1H, J3,4 = 9.4, H-3), 10.0 (bs, 1H, NOH). 13C NMR (CDCl3): δ 20.4, 20.5, 20.6 (MeCO), 20.2 (C-9), 31.1 (C-8), 38.2 (MeSO), 52.7 (C-10), 61.9 (C-6), 67.9 (C-4), 70.1 (C-2), 73.7 (C-3), 75.7 (C-5), 79.7 (C-1), 147.2 (C=N), 169.4, 169.6, 170.2, 170.7 (C=O). HR-ESI-MS m/z calcd for C19H29NO11S2 511.1182, found 511.1177.
  • S-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl) (Z)-5-(methylsulfinyl)pentanethiohydroximate (6c) [28].
White amorphous powder (0.28 g, 53% yield), [α]D -16 (c = 0.6, CHCl3). 1H NMR (CDCl3): δ 1.77–1.91 (m, 4H, H-9, H-10), 1.99, 2.01, 2.03, 2.06 (4s, 12H, MeCO), 2.47–2.55 (m, 2H, H-8), 2.59 (s, 3H, MeSO), 2.68–2.85 (m, 2H, H-11), 3.75 (ddd, 1H, J4,5 = 9.8, H-5), 4.12 (dd, 1H, J5,6b = 2.6, J6a,6b = 12.5, H-6b), 4.18 (dd, 1H, J5,6a = 5.1, H-6a), 4.98–5.11 (m, 3H, H-4, H-1, H-2), 5.25 (dd, 1H, J3,4 = 9.0, H-3), 7.87 (bs, 1H, NOH). 13C NMR (CDCl3): δ 20.4, 20.5, 20.6 (MeCO), 21.9 (C-9), 25.7 (C-10), 32.0 (C-8), 38.1 (MeSO), 53.7 (C-11), 62.0 (C-6), 68.1 (C-4), 70.1 (C-2), 73.7 (C-3), 75.8 (C-5), 79.9 (C-1), 149.7 (C=N), 169.4, 169.5, 170.3, 170.7 (C=O). HR-ESI-MS m/z calcd for C20H31NO11S2 525.1339, found 525.1331.
  • S-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl) (Z)-6-(methylsulfinyl)hexanethiohydroximate (6d).
White amorphous powder (0.28 g, 51% yield), [α]D -15 (c = 1.0, CHCl3). 1H NMR (CDCl3): δ 1.48–1.54 (m, 2H, H-10), 1.66–1.81 (m, 4H, H-9, H-11), 1.98, 2.01, 2.02, 2.05 (4s, 12H, MeCO), 2.47–2.55 (m, 2H, H-8), 2.58 (s, 3H, MeSO), 2.64–2.80 (m, 2H, H-12), 3.74 (ddd, 1H, J4,5 = 9.2, H-5), 4.09 (dd, 1H, J5,6b = 2.6, J6a,6b = 12.5, H-6b), 4.18 (dd, 1H, J5,6a = 5.3, H-6a), 5.00–5.10 (m, 3H, H-4, H-1, H-2), 5.25 (ft, 1H, J3,4 = 9.1, H-3), 9.74 (bs, 1H, NOH). 13C NMR (CDCl3): δ 20.3, 20.5, 20.7 (MeCO), 22.1 (C-9), 26.3, 27.9 (C-10, C-11), 32.0 (C-8), 38.1 (MeSO), 53.9 (C-12), 62.0 (C-6), 68.3 (C-4), 69.9 (C-2), 73.6 (C-3), 75.7 (C-5), 79.8 (C-1), 150.3 (C=N), 169.3, 169.5, 170.3, 170.7 (C=O). HR-ESI-MS m/z calcd for C21H33NO11S2 539.1495, found 539.1492.
  • S-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl) (Z)-8-(methylsulfinyl)octanethiohydroximate (6e).
White amorphous powder (0.34 g, 60% yield), [α]D -13 (c = 1.0, CHCl3). 1H NMR (CDCl3): δ 1.21–1.45 (m, 6H, H-10-H-12), 1.50–1.62 (m, 2H, H-9), 1.63–1.74 (m, 2H, H-13), 1.91, 1.93, 1.94, 1.97 (4s, 12H, MeCO), 2.39–2.47 (m, 2H, H-8), 2.55 (s, 3H, MeSO), 2.51–2.79 (m, 2H, H-14), 3.67 (ddd, 1H, J4,5 = 9.8, H-5), 3.99 (dd, 1H, J5,6b = 2.5, J6a,6b = 11.8, H-6b), 4.10 (dd, 1H, J5,6a = 5.7, H-6a), 4.89–5.02 (m, 3H, H-4, H-1, H-2), 5.18 (ft, 1H, J3,4 = 9.9, H-3), 10.18 (bs, 1H, NOH). 13C NMR (CDCl3): δ 20.2, 20.3 (MeCO), 21.9, 26.4, 28.0, 28.1, 28.2 (C-9-C-13), 31.9 (C-8), 37.8 (MeSO), 53.9 (C-14), 62.0 (C-6), 67.9 (C-4), 69.9 (C-2), 73.5 (C-3), 75.5 (C-5), 79.6 (C-1), 150.1 (C=N), 169.1, 169.4, 170.1, 170.5 (C=O). HR-ESI-MS m/z calcd for C23H37NO11S2 567.1808, found 567.1800.
  • S-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl) (Z)-10-(methylsulfinyl)decanethiohydroximate (6f).
White amorphous powder (0.41 g, 68% yield), [α]D -14 (c = 0.7, CHCl3).1H NMR (CDCl3): δ 1.25–1.41 (m, 10H, H-10-H-14), 1.49–1.65 (m, 4H, H-9, H-15), 1.99, 2.01, 2.02, 2.05 (4s, 12H, MeCO), 2.41–2.49 (m, 2H, H-8), 2.52 (s, 3H, MeSO), 2.51–2.77 (m, 2H, H-16), 3.72 (ddd, 1H, J4,5 = 10.0, H-5), 4.05 (dd, 1H, J5,6b = 2.2, J6a,6b = 12.5, H-6b), 4.26 (dd, 1H, J5,6a = 5.5, H-6a), 5.04–5.13 (m, 3H, H-4, H-1, H-2), 5.24 (ft, 1H, J3,4 = 9.2, H-3), 8.90 (bs, 1H, NOH). 13C NMR (CDCl3): δ 20.3, 20.5, 20.6 (MeCO), 22.7, 26.0, 27.9, 28.0, 29.0, 29.1, 29.2 (C-9-C-15), 32.2 (C-8), 38.4 (MeSO), 53.6 (C-16), 62.0 (C-6), 68.6 (C-4), 70.5 (C-2), 73.7 (C-3), 75.4 (C-5), 79.0 (C-1), 150.7 (C=N), 169.4, 170.4, 170.7 (C=O). HR-ESI-MS m/z calcd for C25H41NO11S2 595.2121, found 595.2111.
  • S-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl) (Z)-12-(methylsulfinyl)dodecanethiohydroximate (6g).
White amorphous powder (0.41 g, 65% yield), [α]D -15 (c = 0.8, CHCl3). 1H NMR (CDCl3): δ 1.33–1.47 (m, 14H, H-10-H-16), 1.50–1.68 (m, 4H, H-9, H-17), 1.98, 2.01, 2.02, 2.05 (4s, 12H, MeCO), 2.44–2.51 (m, 2H, H-8), 2.52 (s, 3H, MeSO), 2.53–2.81 (m, 2H, H-18), 3.74 (ddd, 1H, J4,5 = 10.0, H-5), 4.09 (dd, 1H, J5,6b = 2.4, J6a,6b = 12.3, H-6b), 4.17 (dd, 1H, J5,6a = 5.5, H-6a), 5.01–5.15 (m, 3H, H-4, H-1, H-2), 5.21 (ft, 1H, J3,4 = 9.9, H-3), 10.5 (bs, 1H, NOH). 13C NMR (CDCl3): δ 20.2, 20.3, 20.4 (MeCO), 22.6, 26.8, 28.4, 29.6, 30.0 (C-9-C-17), 32.5 (C-8), 39.2 (MeSO), 53.0 (C-18), 62.1 (C-6), 67.7 (C-4), 70.2 (C-2), 73.4 (C-3), 75.7 (C-5), 79.8 (C-1), 151.3 (C=N), 169.4, 169.5, 170.3, 170.8 (C=O). HR-ESI-MS m/z calcd for C27H45NO11S2 623.2434, found 623.2429.

Selective Oxidation of ω-Sulfides 5 to ω-Sulfones 7

To a stirred solution of the protected glucosyl, thiohydroximate 5 (1 mmol) in methanol (40 mL) cooled at 0 °C, a solution of oxone (3 mmol) in water (10 mL) was added dropwise. After stirring at r.t. for 1–3 h, the white suspension was filtered, and the clear solution was diluted with water (50 mL) and then repeatedly extracted with chloroform (4 × 30 mL). The combined organic phases were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (dichloromethane containing 2–4% v/v methanol) to produce sulfones 7a–g as amorphous solids.
  • S-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl) (Z)-3-(methylsulfonyl)propanethiohydroximate (7a).
White amorphous powder (0.25 g, 49% yield), [α]D -18 (c = 0.6, CHCl3). 1H NMR (CDCl3): δ 1.95, 1.98, 1.99, 2.04 (4s, 12H, MeCO), 2.93 (s, 3H, MeSO2), 2.94–3.12 (m, 2H, H-8), 3.27–3.48 (m, 2H, H-9), 3.81 (ddd, 1H, J4,5 = 10.0, H-5), 4.06 (dd, 1H, J5,6b = 2.6, J6a,6b = 12.5, H-6b), 4.25 (dd, 1H, J5,6a = 4.6, H-6a), 4.95–5.10 (m, 3H, H-4, H-1, H-2), 5.21 (ft, 1H, J3,4 = 9.0, H-3), 9.5 (bs, 1H, NOH). 13C NMR (CDCl3): δ 20.2, 20.3, 20.4 (MeCO), 24.8 (C-8), 40.9 (MeSO2), 51.5 (C-9), 61.5 (C-6), 67.7 (C-4), 69.9 (C-2), 73.6 (C-3), 75.6 (C-5), 79.4 (C-1), 146.9 (C=N), 169.6, 169.7, 170.4, 171.1 (C=O). HR-ESI-MS m/z calcd for C18H27NO12S2 513.0975, found 513.0969.
  • S-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl) (Z)-4-(methylsulfonyl)butanethiohydroximate (7b).
White amorphous powder (0.29 g, 54% yield), [α]D -15 (c = 0.7, CHCl3). 1H NMR (CDCl3): δ 1.95–2.23 (m, 2H, H-9), 1.99, 2.01, 2.03, 2.06 (4s, 12H, MeCO), 2.76 (t, 2H, J = 7.0, H-8), 2.93 (s, 3H, MeSO2), 3.01–3.17 (m, 2H, H-10), 3.84 (ddd, 1H, J4,5 = 10.5, H-5), 4.15 (dd, 1H, J5,6b = 2.3, J6a,6b = 11.8, H-6b), 4.21 (dd, 1H, J5,6a = 5.2, H-6a), 4.99–5.15 (m, 3H, H-4, H-1, H-2), 5.26 (ft, 1H, J3,4 = 9.2, H-3), 9.2 (bs, 1H, NOH). 13C NMR (CDCl3): δ 20.4, 20.5, 20.6 (MeCO), 19.7 (C-9), 30.7 (C-8), 40.6 (MeSO2), 53.1 (C-10), 61.8 (C-6), 67.3 (C-4), 70.1 (C-2), 73.6 (C-3), 75.6 (C-5), 79.6 (C-1), 150.7 (C=N), 169.5, 169.6, 170.3, 170.9 (C=O). HR-ESI-MS m/z calcd for C19H29NO12S2 527.1131, found 527.1124.
  • S-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl) (Z)-5-(methylsulfonyl)pentanethiohydroximate (7c).
White amorphous powder (0.30 g, 56% yield), [α]D -18 (c = 0.8, CHCl3). 1H NMR (CDCl3): δ 1.76–1.94 (m, 4H, H-9, H-10), 1.98, 2.00, 2.02, 2.05 (4s, 12H, MeCO), 2.53–2.60 (m, 2H, H-8), 2.91 (s, 3H, MeSO2), 3.06 (t, 2H, J = 7.3, H-11), 3.77 (ddd, 1H, J4,5 = 10.0, H-5), 4.11 (dd, 1H, J5,6b = 2.1, J6a,6b = 11.6, H-6b), 4.17 (dd, 1H, J5,6a = 4.9, H-6a), 5.01–5.10 (m, 3H, H-4, H-1, H-2), 5.26 (ft, 1H, J3,4 = 9.4, H-3), 9.2 (bs, 1H, NOH). 13C NMR (CDCl3): δ 20.4, 20.5, 20.6 (MeCO), 21.3 (C-9), 25.2 (C-10), 31.6 (C-8), 40.6 (MeSO2), 53.9 (C-11), 62.0 (C-6), 68.0 (C-4), 70.1 (C-2), 73.6 (C-3), 75.7 (C-5), 79.7 (C-1), 151.0 (C=N), 169.4, 169.6, 170.3, 170.8 (C=O). HR-ESI-MS m/z calcd for C20H31NO12S2 541.1288, found 541.1279.
  • S-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl) (Z)-6-(methylsulfonyl)hexanethiohydroximate (7d).
White amorphous powder (0.33 g, 60% yield), [α]D -13 (c = 0.8, CHCl3). 1H NMR (CDCl3): δ 1.47–1.55 (m, 2H, H-10), 1.61–1.69 (m, 2H, H-9), 1.78–1.89 (m, 2H, H-11), 1.96, 1.99, 2.00, 2.03 (4s, 12H, MeCO), 2.44–2.55 (m, 2H, H-8), 2.89 (s, 3H, MeSO2), 3.00 (t, 2H, J = 7.2, H-12), 3.74 (ddd, 1H, J4,5 = 9.5, H-5), 4.08 (dd, 1H, J5,6b = 2.5, J6a,6b = 12.3, H-6b), 4.18 (dd, 1H, J5,6a = 5.1, H-6a), 4.95–5.09 (m, 3H, H-4, H-1, H-2), 5.24 (ft, 1H, J3,4 = 9.0, H-3), 9.2 (bs, 1H, NOH). 13C NMR (CDCl3): δ 20.4, 20.5, 20.6 (MeCO), 21.7 (C-9), 26.0, 27.3 (C-10, C-11), 31.8 (C-8), 40.6 (MeSO2), 54.0 (C-12), 62.0 (C-6), 68.0 (C-4), 70.1 (C-2), 73.5 (C-3), 75.6 (C-5), 79.7 (C-1), 151.6 (C=N), 169.4, 169.5, 170.3, 170.7 (C=O). HR-ESI-MS m/z calcd for C21H33NO12S2 555.1444, found 555.1440.
  • S-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl) (Z)-8-(methylsulfonyl)octanethiohydroximate (7e).
White amorphous powder (0.40 g, 68% yield), [α]D -14 (c = 0.8, CHCl3). 1H NMR (CDCl3): δ 1.24–1.49 (m, 6H, H-10-H-12), 1.55–1.68 (m, 2H, H-9), 1.73–1.89 (m, 2H, H-13), 1.96, 1.99, 2.02, 2.05 (4s, 12H, MeCO), 2.42–2.58 (m, 2H, H-8), 2.88 (s, 3H, MeSO2), 2.99 (t, 2H, J = 7.0, H-14), 3.64 (ddd, 1H, J4,5 = 10.2, H-5), 4.08 (dd, 1H, J5,6b = 2.4, J6a,6b = 12.3, H-6b), 4.17 (dd, 1H, J5,6a = 5.3, H-6a), 5.00–5.09 (m, 3H, H-4, H-1, H-2), 5.26 (ft, 1H, J3,4 = 9.4, H-3), 9.0 (bs, 1H, NOH). 13C NMR (CDCl3): δ 20.3, 20.5, 20.6 (MeCO), 21.8 (C-9), 26.4, 27.8, 28.2, 28.3 (C-10-C-13), 32.0 (C-8), 40.3 (MeSO2), 54.4 (C-14), 62.1 (C-6), 68.0 (C-4), 70.0 (C-2), 73.6 (C-3), 75.7 (C-5), 79.8 (C-1), 151.9 (C=N), 169.3, 169.5, 170.3, 170.7 (C=O). HR-ESI-MS m/z calcd for C23H37NO12S2 583.1756, found 583.1749.
  • S-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl) (Z)-10-(methylsulfonyl)decanethiohydroximate (7f).
White amorphous powder (0.40 g, 65% yield), [α]D -14 (c = 0.7, CHCl3). 1H NMR (CDCl3): δ 1.22–1.41 (m, 10H, H-10-H-14), 1.41–1.57 (m, 2H, H-9), 1.69–1.85 (m, 2H, H-15), 1.98, 2.01, 2.03, 2.06 (4s, 12H, MeCO), 2.42–2.47 (m, 2H, H-8), 2.87 (s, 3H, MeSO2), 2.96 (t, 2H, J = 7.2, H-16), 3.72 (ddd, 1H, J4,5 = 10.1, H-5), 4.16 (dd, 1H, J5,6b = 2.6, J6a,6b = 12.1, H-6b), 4.26 (dd, 1H, J5,6a = 5.6, H-6a), 5.08–5.19 (m, 3H, H-4, H-1, H-2), 5.22 (ft, 1H, J3,4 = 9.8, H-3), 9.80 (bs, 1H, NOH). 13C NMR (CDCl3): δ 20.3, 20.5, (MeCO), 21.7 (C-9), 26.2, 27.9, 29.4, 29.5, 29.9 (C-10-C-15), 32.8 (C-8), 40.7 (MeSO2), 54.0 (C-16), 61.9 (C-6), 68.2 (C-4), 68.5 (C-2), 73.6 (C-3), 76.1 (C-5), 80.0 (C-1), 151.4 (C=N), 169.5, 169.8, 170.8, 171.0 (C=O). HR-ESI-MS m/z calcd for C25H41NO12S2 611.2068, found 611.2061.
  • S-(2,3,4,6-Tetra-O-acetyl-β-d-glucopyranosyl) (Z)-12-(methylsulfonyl)dodecanethiohydroximate (7g).
White amorphous powder (0.45 g, 70% yield), [α]D -13 (c = 0.8, CHCl3). 1H NMR (CDCl3): δ 1.33–1.51 (m, 14H, H-10-H-16), 1.53–1.87 (m, 4H, H-9, H-17), 1.99, 2.01, 2.02, 2.05 (4s, 12H, MeCO), 2.40–2.59 (m, 2H, H-8), 2.89 (s, 3H, MeSO2), 2.99 (t, 2H, J = 7.1, H-18), 3.77 (ddd, 1H, J4,5 = 10.0, H-5), 4.12 (dd, 1H, J5,6b = 2.5, J6a,6b = 12.5, H-6b), 4.23 (dd, 1H, J5,6a = 5.4, H-6a), 4.98–5.20 (m, 3H, H-4, H-1, H-2), 5.26 (ft, 1H, J3,4 = 9.4, H-3), 8.66 (bs, 1H, NOH). 13C NMR (CDCl3): δ 20.1, 20.4, 20.5 (MeCO), 22.6, 27.1, 28.6, 28.8, 29.6, 29.8, 30.3 (C-9-C-17), 32.6 (C-8), 40.7 (MeSO2), 54.6 (C-18), 62.1 (C-6), 67.3 (C-4), 70.7 (C-2), 73.9 (C-3), 75.9 (C-5), 79.6 (C-1), 152.2 (C=N), 169.7, 170.0, 170.4, 170.7 (C=O). HR-ESI-MS m/z calcd for C27H45NO12S2 639.2383, found 639.2375.

3.2.2. Pathway 1 and 2 Common Procedures

General Procedure for NO-Sulfation of the Glucosyl Thiohydroximates 6 and 7

A solution of compound 6 or 7 was treated with sulfur trioxide pyridine complex as previously described in detail [29]. The obtained NO-sulfated compounds 8 or 9 after purification are described as follows.
  • Per-O-acetylated 2-methylsulfinylethyl glucosinolate (8a).
White amorphous powder (0.14 g, 56% yield), [α]D -21 (c = 1.0, MeOH). 1H NMR (DMSO-d6): δ 1.96, 1.98, 2.01, 2.02 (4s, 12H, MeCO), 2.58 (s, 3H, MeSO), 2.59–2.82 (m, 4H, H-8, H-9), 4.10–4.21 (m, 3H, H-5, H-6b, H-6a), 4.87 (t, 1H, J2,3 = 9.6, H-2), 4.92 (t, 1H, J4,5 = 8.8, H-4), 5.43 (t, 1H, J3,4 = 9.5, H-3), 5.58 (d, 1H, J1,2 = 10.0, H-1). 13C NMR (DMSO-d6): δ 20.1, 20.2, 20.3, 20.5 (MeCO), 25.6 (C-8), 38.0 (MeSO), 54.2 (C-9), 61.9 (C-6), 69.4 (C-4), 71.9 (C-2), 74.6 (C-3), 77.9 (C-5), 79.5 (C-1), 153.2 (C=N), 169.5, 170.2, 170.3 (C=O).
  • Per-O-acetylated 3-methylsulfinylpropyl glucosinolate (8b).
White amorphous powder (0.14 g, 54% yield), [α]D -19 (c = 0.9, MeOH). 1H NMR (DMSO-d6): δ 1.83–2.02 (m, 14H, H-9, MeCO), 2.58 (s, 3H, MeSO), 2.68–2.90 (m, 4H, H-8, H-10), 4.00–4.16 (m, 3H, H-5, H-6a, H-6b), 4.86 (t, 1H, J2,3 = 9.6, H-2), 4.93 (t, 1H, J4,5 = 8.0, H-4), 5.37 (t, 1H, J3,4 = 9.3, H-3), 5.51 (d, 1H, J1,2 = 10.2, H-1). 13C NMR (DMSO-d6): δ 20.0, 20.2, 20.3, 20.5 (MeCO), 20.7 (C-9), 32.1 (C-8), 38.8 (MeSO), 54.2 (C-10), 61.9 (C-6), 69.5 (C-4), 72.8 (C-2), 74.4 (C-3), 78.2 (C-5), 79.3 (C-1), 153.3 (C=N), 169.4, 169.5, 169.8, 170.3 (C=O).
  • Per-O-acetylated 4-methylsulfinylbutyl glucosinolate (8c).
White amorphous powder (0.15 g, 58% yield), [α]D -15 (c = 0.6, MeOH). 1H NMR (DMSO-d6): δ 1.65–1.82 (m, 4H, H-9, H-10), 1.97, 2.02, 2.03, 2.05 (4s, 12H, MeCO), 2.59 (s, 3H, MeSO), 2.58–2.89 (m, 4H, H-8, H-11), 4.02–4.21 (m, 3H, H-5, H-6a, H-6b), 4.88 (t, 1H, J2,3 = 9.6, H-2), 4.93 (t, 1H, J4,5 = 8.3, H-4), 5.45 (t, 1H, J3,4 = 9.5, H-3), 5.52 (d, 1H, J1,2 = 10.0, H-1). 13C NMR (DMSO-d6): δ 20.5, 20.6, 20.8 (MeCO), 22.4 (C-9), 26.5 (C-10), 32.7 (C-8), 37.9 (MeSO), 53.9 (C-11), 63.2 (C-6), 69.4 (C-4), 71.3 (C-2), 74.9 (C-3), 76.5 (C-5), 80.6 (C-1), 159.5 (C=N), 171.3, 171.5, 171.7, 172.6 (C=O).
  • Per-O-acetylated 5-methylsulfinylpentyl glucosinolate (8d).
White amorphous powder (0.16 g, 62% yield), [α]D -16 (c = 0.7, MeOH). 1H NMR (CD3OD): δ 1.54–1.68 (m, 2H, H-10), 1.73–1.88 (m, 4H, H-9, H-11), 1.97, 2.02, 2.03, 2.06 (4s, 12H, MeCO), 2.67 (s, 3H, MeSO), 2.72 (t, 2H, J8,9 = 7.2, H-8), 2.79–2.95 (m, 2H, H-12), 4.05 (ddd, 1H, J4,5 = 9.6, H-5), 4.15 (dd, 1H, J5,6b = 2.7, J6a,6b = 12.4, H-6b), 4.23 (dd, 1H, J5,6a = 5.1, H-6a), 4.98 (t, 1H, J2,3 = 9.2, H-2), 5.05 (t, 1H, J4,5 = 8.9, H-4), 5.39–5.43 (m, 2H, H-1, H-3). 13C NMR (CD3OD): δ 20.5, 20.7 (MeCO), 23.0 (C-10), 27.3 (C-9), 28.6 (C-11), 33.0 (C-8), 38.0 (MeSO), 54.5 (C-12), 63.3 (C-6), 69.5 (C-4), 71.4 (C-2), 75.0 (C-3), 76.7 (C-5), 80.8 (C-1), 159.7 (C=N), 171.1, 171.5, 171.7, 172.4 (C=O).
  • Per-O-acetylated 7-methylsulfinylheptyl glucosinolate (8e).
White amorphous powder (0.21 g, 75% yield), [α]D -16 (c = 0.9, MeOH). 1H NMR (DMSO-d6): δ 1.22–1.41 (m, 6H, H-10-H-12), 1.42–1.60 (m, 4H, H-9, H-13), 1.96, 1.98, 1.99, 2.03 (4s, 12H, MeCO), 2.55 (s, 3H, MeSO), 2.56–2.88 (m, 4H, H-8, H-14), 4.05–4.21 (m, 3H, H-5, H-6b, H-6a), 4.82 (t, 1H, J2,3 = 9.4, H-2), 4.93 (t, 1H, J4,5 = 8.9, H-4), 5.47 (t, 1H, J3,4 = 9.6, H-3), 5.50 (d, 1H, J1,2 = 10.1, H-1). 13C NMR (DMSO-d6): δ 20.3, 20.4, 20.5 (MeCO), 22.1, 26.5, 28.1, 28.2, 28.3 (C-9-C-13), 31.7 (C-8), 37.6 (MeSO), 54.0 (C-14), 62.3 (C-6), 68.5 (C-4), 70.1 (C-2), 73.2 (C-3), 74.7 (C-5), 78.7 (C-1), 158.5 (C=N), 169.4, 169.5, 169.9, 170.2 (C=O).
  • Per-O-acetylated 9-methylsulfinylnonyl glucosinolate (8f).
White amorphous powder (0.22 g, 78% yield), [α]D -16 (c = 1.0, MeOH). 1H NMR (DMSO-d6): δ 1.19–1.40 (m, 10H, H-10-H-14), 1.42–1.57 (m, 4H, H-9, H-15), 1.98, 1.99, 2.01, 2.04 (4s, 12H, MeCO), 2.59 (s, 3H, MeSO), 2.58–2.92 (m, 4H, H-8, H-16), 3.99–4.18 (m, 3H, H-5, H-6b, H-6a), 4.89 (t, 1H, J2,3 = 9.5, H-2), 4.91 (t, 1H, J4,5 = 8.7, H-4), 5.43 (t, 1H, J3,4 = 9.7, H-3), 5.51 (d, 1H, J1,2 = 10.1, H-1). 13C NMR (DMSO-d6): δ 20.2, 20.3, 20.4 (MeCO), 21.9, 26.4, 28.2, 28.8, 29.1, 29.4 (C-9-C-15), 32.4 (C-8), 38.2 (MeSO), 53.8 (C-16), 62.2 (C-6), 68.6 (C-4), 70.4 (C-2), 72.9 (C-3), 74.7 (C-5), 78.3 (C-1), 159.7 (C=N), 171.3, 171.5, 171.8, 172.4 (C=O).
  • Per-O-acetylated 11-methylsulfinylundecyl glucosinolate (8g).
White amorphous powder (0.23 g, 76% yield), [α]D -18 (c = 1.1, MeOH). 1H NMR (DMSO-d6): δ 1.22–1.45 (m, 14H, H-10-H-16), 1.47–1.68 (m, 4H, H-9, H-17), 1.97, 1.98, 2.00, 2.03 (4s, 12H, MeCO), 2.58 (s, 3H, MeSO), 2.59–2.86 (m, 4H, H-8, H-18), 4.00–4.26 (m, 3H, H-5, H-6b, H-6a), 4.90 (t, 1H, J2,3 = 9.4, H-2), 4.93 (t, 1H, J4,5 = 8.8, H-4), 5.43 (t, 1H, J3,4 = 9.5, H-3), 5.51 (d, 1H, J1,2 = 10.0, H-1). 13C NMR (DMSO-d6): δ 20.2, 20.4, 20.5 (MeCO), 22.8, 26.6, 28.4, 28.9, 30.1, 30.3, 30.4 (C-9-C-17), 32.9 (C-8), 39.6 (MeSO), 53.6 (C-18), 62.6 (C-6), 68.4 (C-4), 70.1 (C-2), 73.3 (C-3), 75.1 (C-5), 78.6 (C-1), 159.4 (C=N), 171.2, 171.4, 171.7, 172.2 (C=O).
  • Per-O-acetylated 2-methylsulfonylethyl glucosinolate (9a).
White amorphous powder (0.15 g, 58% yield), [α]D -19 (c = 0.9, MeOH). 1H NMR (DMSO-d6): δ 1.97, 1.98, 2.02, 2.05 (4s, 12H, MeCO), 2.56 (t, 2H, J8.9 = 7.3, H-8), 2.96 (s, 3H, MeSO2), 3.17 (t, 2H, J9,8 = 7.6, H-9), 4.12–4.23 (m, 3H, H-5, H-6b, H-6a), 4.85 (t, 1H, J2,3 = 9.4, H-2), 4.91 (t, 1H, J4,5 = 9.8, H-4), 5.44 (t, 1H, J3,4 = 9.4, H-3), 5.54 (d, 1H, J1,2 = 10.0, H-1). 13C NMR (DMSO-d6): δ 20.0, 20.4, 20.5 (MeCO), 25.8 (C-8), 40.5 (MeSO2), 54.1 (C-9), 61.4 (C-6), 67.6 (C-4), 70.0 (C-2), 73.4 (C-3), 75.6 (C-5), 79.4 (C-1), 154.9 (C=N), 169.5, 170.1, 170.3 (C=O).
  • Per-O-acetylated 3-methylsulfonylpropyl glucosinolate (9b).
White amorphous powder (0.14 g, 56% yield), [α]D -21 (c = 1.0, MeOH). 1H NMR (DMSO-d6): δ 1.92–2.03 (m, 2H, H-9), 1.94, 1.97, 1.99, 2.01 (4s, 12H, MeCO), 2.71 (t, 2H, J8.9 = 7.1, H-8), 2.97 (s, 3H, MeSO2), 3.14–3.22 (m, 2H, H-10), 4.04–4.15 (m, 3H, H-5, H-6a, H-6b), 4.87 (t, 1H, J2,3 = 9.1, H-2), 4.94 (t, 1H, J4,5 = 8.5, H-4), 5.39 (t, 1H, J3,4 = 9.9, H-3), 5.50 (d, 1H, J1,2 = 10.6, H-1). 13C NMR (DMSO-d6): δ 20.1, 20.4, 20.6 (MeCO), 22.4 (C-9), 30.5 (C-8), 41.0 (MeSO2), 53.8 (C-10), 61.5 (C-6), 69.1 (C-4), 71.9 (C-2), 74.6 (C-3), 77.7 (C-5), 79.9 (C-1), 158.0 (C=N), 169.4, 169.5, 170.2, 170.4 (C=O).
  • Per-O-acetylated 4-methylsulfonylbutyl glucosinolate (9c).
White amorphous powder (0.16 g, 61% yield), [α]D -16 (c = 0.9, MeOH). 1H NMR (DMSO-d6): δ 1.51–1.84 (m, 4H, H-9, H-10), 1.97, 1.99, 2.00, 2.03 (4s, 12H, MeCO), 2.59 (t, 2H, J8.9 = 7.4, H-8), 2.92 (s, 3H, MeSO2), 3.16 (t, 2H, J = 7.7, H-11), 3.95–4.22 (m, 3H, H-5, H-6a, H-6b), 4.90 (t, 1H, J2,3 = 9.4, H-2), 4.95 (t, 1H, J4,5 = 8.6, H-4), 5.48 (t, 1H, J3,4 = 9.8, H-3), 5.51 (d, 1H, J1,2 = 10.2, H-1). 13C NMR (DMSO-d6): δ 20.4, 20.5, 20.8 (MeCO), 22.1 (C-9), 25.8 (C-10), 31.7 (C-8), 40.8 (MeSO2), 54.8 (C-11), 63.5 (C-6), 69.3 (C-4), 71.3 (C-2), 74.7 (C-3), 76.8 (C-5), 80.9 (C-1), 158.7 (C=N), 170.7, 171.0, 172.4, 172.5 (C=O).
  • Per-O-acetylated 5-methylsulfonylpentyl glucosinolate (9d).
White amorphous powder (0.17 g, 64% yield), [α]D -15 (c = 0.8, MeOH). 1H NMR (CD3OD): δ 1.53–1.65 (m, 2H, H-10), 1.73–1.91 (m, 4H, H-9, H-11), 1.98, 2.02, 2.03, 2.06 (4s, 12H, MeCO), 2.70 (t, 2H, J8.9 = 7.0, H-8), 2.97 (s, 3H, MeSO2), 3.16 (t, 2H, J = 7.8, H-12), 4.02–4.09 (m, 1H, H-5), 4.15 (dd, 1H, J5,6b = 2.2, J6a,6b = 12.1, H6b), 4.22 (dd, 1H, J5,6a = 5.1, H6a), 4.98 (t, 1H, J2,3 = 9.5, H-2), 5.05 (t, 1H, J4,5 = 9.8, H-4), 5.39–5.43 (m, 2H, H-1, H-3). 13C NMR (CD3OD): δ 20.5, 20.7 (MeCO), 22.8 (C-10), 27.2 (C-9), 28.3 (C-11), 32.9 (C-8), 40.7 (MeSO2), 54.9 (C-12), 63.3 (C-6), 69.4 (C-4), 71.3 (C-2), 74.9 (C-3), 76.6 (C-5), 80.7 (C-1), 159.8 (C=N), 171.1, 171.4, 171.7, 172.4 (C=O).
  • Per-O-acetylated 7-methylsulfonylheptyl glucosinolate (9e).
White amorphous powder (0.21 g, 76% yield), [α]D -18 (c = 1.0, MeOH). 1H NMR (DMSO-d6): δ 1.25–1.41 (m, 6H, H-10-H-12), 1.42–1.65 (m, 4H, H-9, H-13), 1.97, 1.98, 1.99, 2.02 (4s, 12H, MeCO), 2.58 (t, 2H, J8.9 = 7.4, H-8), 2.95 (s, 3H, MeSO2), 3.16 (t, 2H, J = 7.9, H-14), 4.03–4.20 (m, 3H, H-5, H-6b, H-6a), 4.89 (t, 1H, J2,3 = 9.5, H-2), 4.91 (t, 1H, J4,5 = 8.7, H-4), 5.43 (t, 1H, J3,4 = 9.7, H-3), 5.51 (d, 1H, J1,2 = 10.1, H-1). 13C NMR (DMSO-d6): δ 20.3, 20.4 (MeCO), 21.5, 26.8, 28.0, 28.5, 28.6 (C-9-C-13), 32.2 (C-8), 40.6 (MeSO2), 54.3 (C-14), 61.5 (C-6), 69.3 (C-4), 71.3 (C-2), 75.2 (C-3), 76.5 (C-5), 80.4 (C-1), 159.8 (C=N), 171.0, 171.3, 171.7, 172.0 (C=O).
  • Per-O-acetylated 9-methylsulfonylnonyl glucosinolate (9f).
White amorphous powder (0.25 g, 85% yield), [α]D -16 (c = 0.9, MeOH). 1H NMR (DMSO-d6): δ 1.21–1.40 (m, 10H, H-10-H-14), 1.42–1.57 (m, 4H, H-9, H-15), 1.98, 1.99, 2.02, 2.04 (MeCO), 2.49–2.61 (m, 2H, H-8), 2.96 (s, 3H, MeSO2), 3.18 (t, 2H, J = 7.6, H-16), 3.99–4.18 (m, 3H, H-5, H-6b, H-6a), 4.81 (t, 1H, J2,3 = 9.4, H-2), 4.93 (t, 1H, J4,5 = 8.9, H-4), 5.47 (t, 1H, J3,4 = 9.6, H-3), 5.50 (d, 1H, J1,2 = 10.1, H-1). 13C NMR (DMSO-d6): δ 20.2, 20.3, 20.4 (MeCO), 21.6, 26.4, 28.1, 29.6, 29.7, 30.0 (C-9-C-15), 33.2 (C-8), 40.9 (MeSO2), 54.3 (C-16), 62.2 (C-6), 69.5 (C-4), 71.4 (C-2), 74.7 (C-3), 76.5 (C-5), 79.9 (C-1), 159.6 (C=N), 171.2, 171.6, 171.9, 172.5 (C=O).
  • Per-O-acetylated 11-methylsulfonylundecyl glucosinolate (9g).
White amorphous powder (0.25 g, 82% yield), [α]D -17 (c = 1.0, MeOH). 1H NMR (DMSO-d6): δ 1.22–1.42 (m, 14H, H-10-H-16), 1.47–1.68 (m, 4H, H-9, H-17), 1.97, 1.99, 2.00, 2.02 (MeCO), 2.53–2.64 (m, 2H, H-8), 2.98 (s, 3H, MeSO2), 3.16 (t, 2H, J = 7.8, H-18), 4.01–4.25 (m, 3H, H-5, H-6b, H-6a), 4.86 (t, 1H, J2,3 = 9.3, H-2), 4.91 (t, 1H, J4,5 = 9.2, H-4), 5.44 (t, 1H, J3,4 = 9.5, H-3), 5.52 (d, 1H, J1,2 = 10.2, H-1). 13C NMR (DMSO-d6): δ 20.2, 20.4, 20.5 (MeCO), 22.3, 27.5, 28.7, 28.9, 29.6, 29.8, 31.0 (C-9-C-17), 32.7 (C-8), 40.5 (MeSO2), 54.0 (C-18), 63.3 (C-6), 70.4 (C-4), 71.4 (C-2), 75.0 (C-3), 77.3 (C-5), 80.4 (C-1), 160.3 (C=N), 171.3, 171.5, 171.9, 172.6 (C=O).

General Procedure for Deprotection of the Glucopyranosyl Moiety

Peracetylated GSLs 8 or 9 were transformed into GSLs 3 or 4 using the general de-O-acetylation procedure previously described in full detail [29].
  • 2-(Methylsulfinyl)ethyl glucosinolate (3a) [443340-10-1].
White amorphous powder (0.084 g, 82% yield), [α]D -23 (c = 0.7, H2O). 1H NMR (D2O): δ 2.54 (s, 3H, MeSO), 2.85–2.91 (m, 2H, H-8), 2.99–3.06 (m, 2H, H-9), 3.38–3.46 (m, 2H, H-2, H-4), 3.53–3.62 (m, 2H, H-5, H-3), 3.71 (dd, 1H, J5,6b = 5.7, J6a,6b = 12.9, H-6b), 3.88 (dd, 1H, J5,6a = 2.5, H-6a), 5.02 (d, 1H, J1,2 = 10.3, H-1). 13C NMR (D2O): δ 25.5 (C-8), 37.9 (MeSO), 52.7 (C-9), 62.4 (C-6), 70.6 (C-4), 73.7 (C-2), 79.0 (C-3), 81.8 (C-5), 83.9 (C-1), 165.1 (C=N). HR-ESI-MS m/z calcd for C10H18NO10S3 [M−H]− 408.0093, found 408.0084.
  • 3-(Methylsulfinyl)propyl glucosinolate (3b). Glucoiberin [554-88-1].
White amorphous powder (0.085 g, 80% yield), [α]D -19 (c = 0.7, H2O). 1H NMR (D2O): δ 1.96–2.06 (m, 2H, H-9), 2.56 (s, 3H, MeSO), 2.77 (t, 2H, J = 6.8, H-8), 2.82 (t, 2H, J = 6.8, H-10), 3.25–3.32 (m, 2H, H-2, H-4), 3.39–3.46 (m, 2H, H-5, H-3), 3.55 (dd, 1H, J5,6b = 5.7, J6a,6b = 12.5, H-6b), 3.74 (dd, 1H, J5,6a = 2.6, H-6a), 4.91 (d, 1H, J1,2 = 10.0, H-1). 13C NMR (D2O): δ 21.7 (C-9), 32.8 (C-8), 38.8 (MeSO), 54.2 (C-10), 61.8 (C-6), 70.4 (C-4), 73.2 (C-2), 78.6 (C-3), 81.6 (C-5), 83.7 (C-1), 165.2 (C=N) [33]. HR-ESI-MS m/z calcd for C11H20NO10S3 [M−H]− 422.0249, found 422.0239.
  • 4-(Methylsulfinyl)butyl glucosinolate (3c). Glucoraphanin [21414-41-5].
White amorphous powder (0.092 g, 84% yield), [α]D -19 (c = 0.7, H2O). 1H NMR (D2O): δ 1.72–1.98 (m, 4H, H-9, H-10), 2.58 (s, 3H, MeSO), 2.56–2.88 (m, 4H, H-8, H-11), 3.40–3.49 (m, 2H, H-2, H-4), 3.55–3.64 (m, 2H, H-5, H-3), 3.69 (dd, 1H, J5,6b = 5.8, J6a,6b = 13.2, H-6b), 3.90 (dd, 1H, J5,6a = 2.6, H-6a), 5.00 (d, 1H, J1,2 = 10.1, H-1). 13C NMR (D2O): δ 22.7, 26.9, 32.2, 37.9 (C-8-C-11), 54.0 (MeSO), 61.9, 71.3, 73.5, 79.4, 82.4, 83.3 (C-1-C-6), 164.8 (C=N). [34]. HR-ESI-MS m/z calcd for C12H22NO10S3 [M−H]− 436.0406, found 436.0397.
  • 5-(Methylsulfinyl)pentyl glucosinolate (3d). Glucoalyssin [499-37-6].
White amorphous powder (0.098 g, 87% yield), [α]D -19 (c = 0.8, H2O). 1H NMR (D2O): δ 1.52–1.65 (m, 2H, H-10), 1.74–1.90 (m, 4H, H-9, H-11), 2.60 (s, 3H, MeSO), 2.68–2.75 (m, 2H, H-8), 2.75–2.93 (m, 2H, H-12), 3.42–3.48 (m, 2H, H-2, H-4), 3.53–3.59 (m, 2H, H-5, H-3), 3.72 (dd, 1H, J5,6b = 5.8, J6a,6b = 12.8, H-6b), 3.80 (dd, 1H, J5,6a = 2.7, H-6a), 5.08 (d, 1H, J1,2 = 10.0, H-1). 13C NMR (D2O): δ 22.3, 27.4, 29.0, 32.7, 38.2 (C-8-C-12), 54.9 (MeSO), 61.9, 70.5, 73.3, 78.9, 81.3, 83.6 (C-1-C-6), 164.9 (C=N). [35]. HR-ESI-MS m/z calcd for C13H24NO10S3 [M−H]− 450.0562, found 450.0553.
  • 7-(Methylsulfinyl)heptyl glucosinolate (3e). Glucoibarin [112572-51-7].
White amorphous powder (0.108 g, 91% yield), [α]D -21 (c = 0.9, H2O). 1H NMR (D2O): δ 1.20–1.44 (m, 6H, H-10-H-12), 1.47–1.61 (m, 4H, H-9, H-13), 2.54 (s, 3H, MeSO), 2.55–2.86 (m, 4H, H-8, H-14), 3.45–3.51 (m, 2H, H-2, H-4), 3.54–3.68 (m, 2H, H-5, H-3), 3.69 (dd, 1H, J5,6b = 5.7, J6a,6b = 12.5, H-6b), 3.85 (dd, 1H, J5,6a = 2.6, H-6a), 4.97 (d, 1H, J1,2 = 10.0, H-1). 13C NMR (D2O): δ 21.8, 26.5, 28.0, 28.2, 32.1, 37.9 (C-8-C-14), 54.5 (MeSO), 61.2, 70.5, 73.1, 78.9, 81.7, 83.3 (C-1-C-6), 164.6 (C=N). HR-ESI-MS m/z calcd for C15H28NO10S3 [M−H]− 478.0874, found 478.0862.
  • 9-(Methylsulfinyl)nonyl glucosinolate (3f). Glucoarabin [67920-64-3].
White amorphous powder (0.117 g, 93% yield), [α]D -21 (c = 1.0, H2O). 1H NMR (D2O): δ 1.22–1.43 (m, 10H, H-10-H-14), 1.45–1.59 (m, 4H, H-9, H-15), 2.57 (s, 3H, MeSO), 2.58–2.91 (m, 4H, H-8, H-16), 3.39–3.47 (m, 2H, H-2, H-4), 3.55–3.67 (m, 2H, H-5, H-3), 3.71 (dd, 1H, J5,6b = 5.8, J6a,6b = 12.8, H-6b), 3.90 (dd, 1H, J5,6a = 2.6, H-6a), 5.07 (d, 1H, J1,2 = 10.1, H-1). 13C NMR (D2O): δ 22.9, 26.8, 28.1, 28.9, 29.2 (br), 29.5, 32.7, 38.0 (C-8-C-16), 54.4 (MeSO), 61.7, 70.7, 73.3, 78.3, 82.0, 83.4 (C-1-C-6), 164.9 (C=N) [36,37]. HR-ESI-MS m/z calcd for C17H32NO10S3 [M−H]− 506.1187, found 506.1180.
  • 11-(Methylsulfinyl)undecyl glucosinolate (3g) [186037-18-3].
White amorphous powder (0.121 g, 92% yield), [α]D -19 (c = 0.7, H2O). 1H NMR (D2O): δ 1.21–1.40 (m, 14H, H-10-H-16), 1.42–1.68 (m, 4H, H-9, H-17), 2.58 (s, 3H, MeSO), 2.59–2.85 (m, 4H, H-8, H-18), 3.39–3.48 (m, 2H, H-2, H-4), 3.57–3.69 (m, 2H, H-5, H-3), 3.68 (dd, 1H, J5,6b = 5.7, J6a,6b = 13.0, H-6b), 3.90 (dd, 1H, J5,6a = 2.6, H-6a), 5.06 (d, 1H, J1,2 = 10.0, H-1). 13C NMR (D2O): δ 22.6, 26.9, 28.7br, 28.9, 29.6 (br), 29.9, 30.0, 32.7, 39.7 (C-8-C-18), 54.3 (MeSO), 62.3, 70.1, 73.4, 78.9, 81.6, 83.0 (C-1-C-6), 165.1 (C=N). HR-ESI-MS m/z calcd for C19H36NO10S3 [M−H]− 534.1501, found 534.1497.
  • 2-(Methylsulfonyl)ethyl glucosinolate (4a).
White amorphous powder (0.085 g, 80% yield), [α]D -21 (c = 0.8, H2O). 1H NMR (D2O): δ 2.58 (t, 2H, J = 7.6, H-8), 2.95 (s, 3H, MeSO2), 3.17 (t, 2H, J = 7.5, H-9), 3.42–3.51 (m, 2H, H-2, H-4), 3.54–3.67 (m, 2H, H-5, H-3), 3.65 (dd, 1H, J5,6b = 5.7, J6a,6b = 13.2, H-6b), 3.88 (dd, 1H, J5,6a = 2.6, H-6a), 5.09 (d, 1H, J1,2 = 10.1, H-1). 13C NMR (D2O): δ 25.9 (C-8), 40.8 (C-9), 53.5 (MeSO2), 61.9, 70.9, 73.2, 79.0, 81.7, 83.9 (C-1-C-6), 163.9 (C=N). HR-ESI-MS m/z calcd for C10H18NO11S3 [M−H]− 424.0042, found 424.0031.
  • 3-(Methylsulfonyl)propyl glucosinolate (4b). Glucocheirolin [15592-36-6].
White amorphous powder (0.093 g, 85% yield), [α]D -20 (c = 0.8, H2O). 1H NMR (D2O): δ 1.95–2.06 (m, 2H, H-9), 2.70 (t, 2H, J = 7.5, H-8), 2.99 (s, 3H, MeSO2), 3.21 (t, 2H, J = 7.3, H-10), 3.45–3.56 (m, 2H, H-2, H-4), 3.58–3.67 (m, 2H, H-5, H-3), 3.72 (dd, 1H, J5,6b = 5.8, J6a,6b = 13.1, H-6b), 3.93 (dd, 1H, J5,6a = 2.7, H-6a), 5.09 (d, 1H, J1,2 = 10.2, H-1). 13C NMR (D2O): δ 21.9, 31.1, 40.7 (C-8-C-10), 54.2 (MeSO2), 61.8, 70.8, 73.3, 78.9, 81.5, 83.5 (C-1-C-6), 164.5 (C=N). HR-ESI-MS m/z calcd for C11H20NO11S3 [M−H]− 438.0198, found 438.0184.
  • 4-(Methylsulfonyl)butyl glucosinolate (4c). Glucoerysolin [22149-26-4].
White amorphous powder (0.098 g, 87% yield), [α]D -22 (c = 1.1, H2O). 1H NMR (D2O): δ 1.48–1.81 (m, 4H, H-9, H-10), 2.56 (t, 2H, J = 7.4, H-8), 2.96 (s, 3H, MeSO2), 3.16 (t, 2H, J = 7.3, H-11), 3.40–3.54 (m, 2H, H-2, H-4), 3.56–3.66 (m, 2H, H-5, H-3), 3.76 (dd, 1H, J5,6b = 5.8, J6a,6b = 13.1, H-6b), 3.91 (dd, 1H, J5,6a = 2.6, H-6a), 5.09 (d, 1H, J1,2 = 10.0, H-1). 13C NMR (D2O): δ 22.6, 26.4, 32.2, 40.9 (C-8-C-11), 54.9 (MeSO2), 61.5, 70.9, 73.2, 79.2, 81.7, 84.1 (C-1-C-6), 165.0 (C=N). HR-ESI-MS m/z calcd for C12H22NO11S3 [M−H]− 452.0355, found 452.0343.
  • 5-(Methylsulfonyl)pentyl glucosinolate (4d) [666235-38-7].
White amorphous powder (0.105 g, 90% yield), [α]D -21 (c = 0.8, H2O). 1H NMR (D2O): δ 1.52–1.64 (m, 2H, H-10), 1.69–1.94 (m, 4H, H-9, H-11), 2.68 (t, 2H, J = 7.7, H-8), 2.98 (s, 3H, MeSO2), 3.18 (t, 2H, J = 7.4, H-12), 3.44–3.52 (m, 2H, H-2, H-4), 3.55–3.68 (m, 2H, H-5, H-3), 3.74 (dd, 1H, J5,6b = 5.8, J6a,6b = 13.2, H-6b), 3.89 (dd, 1H, J5,6a = 2.7, H-6a), 5.09 (d, 1H, J1,2 = 10.2, H-1). 13C NMR (D2O): δ 22.8, 26.9, 28.0, 32.4, 40.9 (C-8-C-12), 54.6 (MeSO2), 62.4, 71.5, 73.2, 78.9, 82.2, 83.6 (C-1-C-6), 165.1 (C=N). HR-ESI-MS m/z calcd for C13H24NO11S3 [M−H]− 466.0511, found 466.0501.
  • 7-(Methylsulfonyl)heptyl glucosinolate (4e) [862388-51-0].
White amorphous powder (0.110 g, 90% yield), [α]D -18 (c = 0.8, H2O). 1H NMR (D2O): δ 1.24–1.42 (m, 6H, H-10-H-12), 1.43–1.64 (m, 4H, H-9, H-13), 2.48–2.61 (m, 2H, H-8), 2.96 (s, 3H, MeSO2), 3.18 (t, 2H, J = 7.8, H-14), 3.44–3.52 (m, 2H, H-2, H-4), 3.58–3.65 (m, 2H, H-5, H-3), 3.71 (dd, 1H, J5,6b = 5.8, J6a,6b = 13.1, H-6b), 3.89 (dd, 1H, J5,6a = 2.7, H-6a), 5.03 (d, 1H, J1,2 = 10.0, H-1). 13C NMR (D2O): δ 21.8, 26.4, 27.8, 28.2, 28.3, 32.4, 40.5 (C-8-C-14), 54.5 (MeSO2), 61.8, 70.7, 73.0, 79.3, 81.6, 83.3 (C-1-C-6), 164.0 (C=N). HR-ESI-MS m/z calcd for C15H28NO11S3 [M−H]− 494.0823, found 494.0815.
  • 9-(Methylsulfonyl)nonyl glucosinolate (4f) [192580-85-1].
White amorphous powder (0.121 g, 94% yield), [α]D -21 (c = 0.9, H2O). 1H NMR (D2O): δ 1.22–1.40 (m, 10H, H-10-H-14), 1.42–1.65 (m, 4H, H9, H15), 2.51–2.66 (m, 2H, H-8), 2.98 (s, 3H, MeSO2), 3.16 (t, 2H, J = 7.4, H-16), 3.41–3.49 (m, 2H, H-2, H-4), 3.55–3.67 (m, 2H, H-5, H-3), 3.75 (dd, 1H, J5,6b = 5.8, J6a,6b = 13.1, H-6b), 3.92 (dd, 1H, J5,6a = 2.6, H-6a), 5.04 (d, 1H, J1,2 = 10.1, H-1). 13C NMR (D2O): δ 22.5, 26.6, 27.8, 29.5, 29.6br, 30.0, 32.9, 40.1 (C-8-C-16), 54.2 (MeSO2), 62.2, 71.2, 73.4, 79.0, 81.5, 83.8 (C-1-C-6), 165.2 (C=N) [38]. HR-ESI-MS m/z calcd for C17H32NO11S3 [M−H]− 522.1136, found 522.1122.
  • 11-(Methylsulfonyl)undecyl glucosinolate (4g).
White amorphous powder (0.129 g, 95% yield), [α]D -20 (c = 0.8, H2O). 1H NMR (D2O): δ 1.22–1.44 (m, 14H, H-10-H-16), 1.45–1.69 (m, 4H, H-9, H-17), 2.50–2.65 (m, 2H, H-8), 2.98 (s, 3H, MeSO2), 3.15 (t, 2H, J = 7.6, H-18), 3.43–3.50 (m, 2H, H-2, H-4), 3.52–3.63 (m, 2H, H-5, H-3), 3.73 (dd, 1H, J5,6b = 5.8, J6a,6b = 13.2, H-6b), 3.91 (dd, 1H, J5,6a = 2.7, H-6a), 5.09 (d, 1H, J1,2 = 10.1, H-1). 13C NMR (D2O): δ 22.6, 27.6, 28.9, 29.0br, 29.8, 30.0, 30.4br, 33.6, 40.6 (C-8-C-18), 54.6 (MeSO2), 61.7, 70.4, 73.2, 78.6, 82.4, 83.6 (C-1-C-6), 165.2 (C=N). HR-ESI-MS m/z calcd for C19H36NO11S3 [M−H]− 550.1449, found 550.1442.

3.2.3. Pathway 2

Selective Oxidation of ω-Methylsulfanylnitroalkanes 10 to ω-Sulfoxides 11

ω-Methylsulfanylnitroalkanes 10a–g were obtained as previously described in [29]. To a stirred solution of ω-methylsulfanylnitroalkane, 10 (12 mmol) in methanol (70 mL) cooled at 0 °C, an ice-cold solution of NaIO4 (25 mmol) in water (35 mL) was added dropwise. After stirring at r.t. for 1.5–3 h, the mixture was filtered, and the clear solution was diluted with water (100 mL) and then repeatedly extracted with chloroform (4 × 50 mL). The combined organic phases were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (dichloromethane containing 3–25% v/v methanol) to produce sulfoxides 11a–g as viscous oils or waxy solids.
  • (1-Methylsulfinyl)-3-nitropropane (11a).
Yellowish oil (1.09 g, 60% yield). 1H NMR (CDCl3): δ 2.34–2.43 (m, 2H, H-2), 2.52 (s, 3H, MeSO), 2.69 (t, 2H, J1,2 = 7.3, H-1), 4.50 (t, 2H, J3,2 = 6.8, H-3). 13C NMR (CDCl3): δ 20.7 (C-2), 38.2 (MeSO), 49.9 (C-1), 73.5 (C-3). C4H9NO3S MS IS m/z = 152.2 [M+H]+.
  • (1-Methylsulfinyl)-4-nitrobutane (11b).
Yellowish oil (1.25 g, 63% yield). 1H NMR (CDCl3): δ 1.76–1.84 (m, 2H, H-2), 2.04–2.13 (m, 2H, H-3), 2.49 (s, 3H, MeSO), 2.65 (t, 2H, J1,2 = 7.3, H-1), 4.36 (t, 2H, J4,3 = 6.8, H-4). 13C NMR (CDCl3): δ 23.3 (C-2), 25.8 (C-3), 38.2 (MeSO), 52.8 (C-1), 74.6 (C-4). C5H11NO3S MS IS m/z = 166.2 [M+H]+.
  • (1-Methylsulfinyl)-5-nitropentane (11c).
Yellowish oil (1.76 g, 82% yield). 1H NMR (CDCl3): δ 1.39–1.53 (m, 2H, H-3), 1.69–1.80 (m, 2H, H-2), 1.92–2.01 (m, 2H, H-4), 2.48 (s, 3H, MeSO), 2.56–2.65 (m, 2H, H-1), 4.32 (t, 2H, J5,4 = 6.8, H-5). 13C NMR (CDCl3): δ 21.6 (C-2), 25.1 (C-3), 26.5 (C-4), 38.3 (MeSO), 53.6 (C-1), 74.9 (C-5). C6H13NO3S MS IS m/z = 180.2 [M+H]+.
  • (1-Methylsulfinyl)-6-nitrohexane (11d).
Yellowish wax (2.06 g, 89% yield). 1H NMR (CDCl3): δ 1.26–1.46 (m, 4H, H-3, H-4), 1.61–1.71 (m, 2H, H-2), 1.85–1.94 (m, 2H, H-5), 2.44 (s, 3H, MeSO), 2.52–2.60 (m, 2H, H-1), 4.27 (t, 2H, J6,5 = 6.8, H-6). 13C NMR (CDCl3): δ 21.8 (C-2), 25.4 (C-3), 26.5 (C-4), 27.5 (C-5), 38.1 (MeSO), 53.8 (C-1), 75.1 (C-6). C7H15NO3S MS IS m/z = 194.3 [M+H]+.
  • (1-Methylsulfinyl)-8-nitrooctane (11e).
Yellowish wax (2.34 g, 88% yield). 1H NMR (CDCl3): δ 1.22–1.41 (m, 8H, H-3-H-6), 1.63–1.70 (m, 2H, H-2), 1.85–1.95 (m, 2H, H-7), 2.48 (s, 3H, MeSO), 2.55–2.67 (m, 2H, H-1), 4.30 (t, 2H, J8,7 = 7.0, H-8). 13C NMR (CDCl3): δ 22.1 (C-2), 27.0 (C-7), 25.8, 28.2, 28.5 (C-3-C-6), 38.3 (MeSO), 54.3 (C-1), 75.4 (C-8). C9H19NO3S MS IS m/z = 222.3 [M+H]+.
  • (1-Methylsulfinyl)-10-nitrodecane (11f).
Yellowish wax (2.81 g, 94% yield). 1H NMR (CDCl3): δ 1.25–1.44 (m, 12H, H-3-H-8), 1.66–1.74 (m, 2H, H-2), 1.90–1.99 (m, 2H, H-9), 2.51 (s, 3H, MeSO), 2.58–2.71 (m, 2H, H-1), 4.33 (t, 2H, J10,9 = 7.0, H-10). 13C NMR (CDCl3): δ 22.3 (C-2), 27.1 (C-9), 25.9, 28.5, 28.9, 29.2 (C-3-C-8), 38.4 (MeSO), 54.5 (C-1), 75.6 (C-10). C11H23NO3S MS IS m/z = 250.4 [M+H]+.
  • (1-Methylsulfinyl)-12-nitrododecane (11g).
Yellowish wax (3.06 g, 92% yield). 1H NMR (CDCl3): δ 1.19–1.43 (m, 16H, H-3-H-10), 1.63–1.73 (m, 2H, H-2), 1.88–1.98 (m, 2H, H-11), 2.49 (s, 3H, MeSO), 2.56–2.68 (m, 2H, H-1), 4.31 (t, 2H, J12,11 = 7.1, H-12). 13C NMR (CDCl3): δ 22.3 (C-2), 27.1 (C-11), 25.9, 28.5, 28.9, 29.0, 29.1 (C-3-C-10), 38.3 (MeSO), 54.5 (C-1), 75.5 (C-12). C13H27NO3S MS IS m/z = 278.4 [M+H]+.

Selective Oxidation of ω-Methylsulfanylnitroalkanes 10 to ω-Sulfones 12

To a stirred solution of ω-methylsulfanylnitroalkane, 10 (10 mmol) in methanol (80 mL) cooled at 0 °C, a solution of oxone (30 mmol) in water (45 mL) was added dropwise. After stirring at r.t. for 2–3 h, the white suspension was filtered, and the clear solution was concentrated (below 30 °C) in vacuo, then repeatedly extracted with chloroform (4 × 50 mL). The combined organic phases were dried over Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography (dichloromethane containing 3–25% v/v methanol) to produce sulfones 12a–g as viscous oils or waxy solids.
  • (1-Methylsulfonyl)-3-nitropropane (12a).
Yellowish oil (1.20 g, 72% yield). 1H NMR (CDCl3): δ 2.46–2.56 (m, 2H, H-2), 2.94 (s, 3H, MeSO2), 3.16 (t, 2H, J1,2 = 7.3, H-1), 4.59 (t, 2H, J3,2 = 6.4, H-3). 13C NMR (CDCl3): δ 19.7 (C-2), 40.8 (MeSO2), 50.8 (C-1), 72.9 (C-3). C4H9NO4S MS IS m/z = 168.2 [M+H]+.
  • (1-Methylsulfonyl)-4-nitrobutane (12b).
Yellowish oil (1.59 g, 88% yield). 1H NMR (CDCl3): δ 1.82–1.93 (m, 2H, H-2), 2.06–2.16 (m, 2H, H-3), 2.86 (s, 3H, MeSO2), 3.03 (t, 2H, J1,2 = 7.5, H-1), 4.40 (t, 2H, J4,3 = 6.8, H-4). 13C NMR (CDCl3): δ 19.0 (C-2), 25.4 (C-3), 40.4 (MeSO2), 53.1 (C-1), 74.4 (C-4). C5H11NO4S MS IS m/z = 182.2 [M+H]+.
  • (1-Methylsulfonyl)-5-nitropentane (12c).
Yellowish wax (1.83 g, 94% yield). 1H NMR (CDCl3): δ 1.48–1.58 (m, 2H, H-3), 1.82–1.92 (m, 2H, H-2), 1.97–2.07 (m, 2H, H-4), 2.88 (s, 3H, MeSO2), 3.00 (ft, 2H, J1,2 = 8.0, H-1), 4.38 (t, 2H, J5,4 = 6.8, H-5). 13C NMR (CDCl3): δ 21.4 (C-2), 24.9 (C-3), 26.5 (C-4), 40.5 (MeSO2), 53.9 (C-1), 74.9 (C-4). C6H13NO4S MS IS m/z = 196.2 [M+H]+.
  • (1-Methylsulfonyl)-6-nitrohexane (12d).
Yellowish wax (1.92 g, 92% yield). 1H NMR (CDCl3): δ 1.37–1.52 (m, 4H, H-3, H-4), 1.78–1.86 (m, 2H, H-2), 1.94–2.04 (m, 2H, H-5), 2.87 (s, 3H, MeSO2), 2.98 (ft, 2H, J1,2 = 8.0, H-1), 4.36 (t, 2H, J6,5 = 6.8, H-6). 13C NMR (CDCl3): δ 21.8 (C-2), 25.5 (C-3), 27.3 (C-4), 40.4 (MeSO2), 54.2 (C-1), 75.3 (C-6). C7H15NO4S MS IS m/z = 210.3 [M+H]+.
  • (1-Methylsulfonyl)-8-nitrooctane (12e).
Yellowish wax (2.28 g, 96% yield). 1H NMR (CDCl3): δ 1.36–1.50 (m, 8H, H-3-H-6), 1.80–1.89 (m, 2H, H-2), 1.95–2.04 (m, 2H, H-7), 2.89 (s, 3H, MeSO2), 2.99 (ft, 2H, J1,2 = 8.0, H-1), 4.37 (t, 2H, J8,7 = 6.8, H-8). 13C NMR (CDCl3): δ 22.0 (C-2), 27.0 (C-7), 25.8, 27.9, 28.2, 28.4 (C-3-C-6), 40.3 (MeSO2), 54.5 (C-1), 75.5 (C-8). C9H19NO4S MS IS m/z = 238.3 [M+H]+.
  • (1-Methylsulfonyl)-10-nitrodecane (12f).
Yellowish wax (2.60 g, 98% yield). 1H NMR (CDCl3): δ 1.25–1.46 (m, 12H, H-3-H-8), 1.78–1.89 (m, 2H, H-2), 1.95–2.02 (m, 2H, H-9), 2.89 (s, 3H, MeSO2), 2.99 (ft, 2H, J1,2 = 8.0, H-1), 4.37 (t, 2H, J10,9 = 6.8, H-10). 13C NMR (CDCl3): δ 22.2 (C-2), 27.1 (C-9), 25.9, 28.1, 28.5, 28.7, 28.8 (C-3-C-8), 40.3 (MeSO2), 54.6 (C-1), 75.6 (C-10). C11H23NO4S MS IS m/z = 266.4 [M+H]+.
  • (1-Methylsulfonyl)-12-nitrododecane (12g).
Yellowish wax (2.79 g, 95% yield). 1H NMR (CDCl3): δ 1.26–1.46 (m, 16H, H-3-H-10), 1.79–1.89 (m, 2H, H-2), 1.94–2.02 (m, 2H, H-11), 2.89 (s, 3H, MeSO2), 2.99 (ft, 2H, J1,2 = 8.0, H-1), 4.37 (t, 2H, J12,11 = 6.8, H-12). 13C NMR (CDCl3): δ 22.2 (C-2), 28.2 (C-11), 26.0, 28.2, 28.6, 28.8, 29.0, 29.1, 29.2 (C-3-C-10), 40.3 (MeSO2), 54.7 (C-1), 75.7 (C-12). C13H27NO4S MS IS m/z = 294.4 [M+H]+.

General Procedure for Nitronate Chlorination and Coupling with the Thioglucose Unit

The nitro derivatives 11 or 12 were transformed into the target thiohydroximates 6 or 7 through a three-step strategy involving a. nitronate formation, b. conversion of nitronate into hydroximoyl chloride and final c. coupling with 2,3,4,6-tetra-O-acetyl-1-thio-β-d-glucopyranose, according to a well-established procedure previously reported in full detail [29]. The glycosyl thiohydroximates 6 or 7 were obtained as amorphous solids. The yield range was 30–54% for the ω-methylsulfinylalkyl thiohydroximates 6 and 35–55% for their ω-methylsulfonylalkyl counterparts 7. The yield for each compound is presented in Table 2. 6a–g and 7a–g were described above in Section 3.2.1.

4. Conclusions

We developed two general pathways for the synthesis of biologically critical ω-methylsulfinylalkyl GSLs and their ω-methylsulfonylalkyl counterparts. A first approach based on selective sulfur oxidation of a range of ω-methylsulfanyl analogs proved practicable, delivering the expected thiofunctionalized GSLs in moderate overall yields. An alternative method involving tailor-made ω-methylsulfinyl- and ω-methylsulfonyl nitroalkanes was also developed. Using a well-established protocol, those nitroalkanes precursors were converted into transient nitrile oxides to be coupled with O-protected 1-thio-β-d-glucopyranose, producing the intermediate thiohydroximates in a slightly higher overall yield, compared to the first approach. In conclusion, both synthetic pathways make available attractive GSLs with a thiofunctionalyzed aglycon chain for biological studies. Noteworthy, the biological activity of intact GSLs has been long overlooked in favor of a large number of studies on their renowned hydrolysis product ITCs. Emerging evidence suggests that GSLs are endowed with biological properties mediated by H2S-releasing or -inducing properties that require further elucidation.

Author Contributions

Conceptualization and methodology, P.R. and M.M.; investigation and experimental, M.M.; writing—original draft preparation, P.R., G.R.D.N., and S.M.; writing—review and editing, S.C. and G.R.D.N. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Data are contained within the article.

Acknowledgments

The authors are grateful to Vassilis Dourtoglou (Vioryl S.A., Afidnes, Greece) and the Greek-French Platon PHC Program. The multiform support of Gérald Guillaumet (Université d’Orléans) is sincerely acknowledged.

Conflicts of Interest

The authors declare no conflicts of interest.

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Molecules 30 00704 g001
Figure 1. Glucosinolate (GSL) general structure 1 and their myrosinase-catalyzed hydrolysis to isothiocyanates (ITCs).
Figure 1. Glucosinolate (GSL) general structure 1 and their myrosinase-catalyzed hydrolysis to isothiocyanates (ITCs).
Molecules 30 00704 g001
Molecules 30 00704 g002
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.
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.
Molecules 30 00704 g002
Molecules 30 00704 sch001
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 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.
Molecules 30 00704 sch001
Molecules 30 00704 sch002
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.
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.
Molecules 30 00704 sch002
Molecules 30 00704 g003
Figure 3. Methods to generate nitrile oxides.
Figure 3. Methods to generate nitrile oxides.
Molecules 30 00704 g003
Molecules 30 00704 sch003
Scheme 3. Pathway 2a—oxidation of sulfide precursors 10a–g [29] to sulfoxides 11a–g or sulfones 12a–g.
Scheme 3. Pathway 2a—oxidation of sulfide precursors 10a–g [29] to sulfoxides 11a–g or sulfones 12a–g.
Molecules 30 00704 sch003
Molecules 30 00704 sch004
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.
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.
Molecules 30 00704 sch004
Table 1. Pathway 1—synthesis of protected glucosyl thiohydroximate 6a–g and 7a–g by selective oxidation of ω-methylsulfanylalkyl precursors 5a–g.
Table 1. Pathway 1—synthesis of protected glucosyl thiohydroximate 6a–g and 7a–g by selective oxidation of ω-methylsulfanylalkyl precursors 5a–g.
Chain Size (n)cpdYield (%) [29]cpdYield (%)Overall
Yield (%)		cpdYield (%)Overall
Yield (%)
25a326a42137a4916
35b346b49177b5418
45c406c53217c5622
55d486d51247d6029
75e476e60287e6832
95f516f68357f6533
115g566g65367g7039
Table 2. Pathway 2—synthesis of protected glucosyl thiohydroximate 6a–g and 7a–g by nitronate chlorination and coupling with the thioglucose unit approach.
Table 2. Pathway 2—synthesis of protected glucosyl thiohydroximate 6a–g and 7a–g by nitronate chlorination and coupling with the thioglucose unit approach.
Chain Size (n)cpdYield (%)cpdYield (%)Overall
Yield (%)		cpdYield (%) cpdYield (%) Overall Yield (%)
211a606a301812a727a3525
311b636b312012b887b3632
411c826c383112c947c4038
511d896d464112d927d4541
711e886e454012e967e4846
911f946f545112f987f5251
1111g926g514712g957g5552
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Mavratzotis, M.; Cassel, S.; De Nicola, G.R.; Montaut, S.; Rollin, P. Synthesis of ω-Methylsulfinyl- and ω-Methylsulfonylalkyl Glucosinolates. Molecules 2025, 30, 704. https://doi.org/10.3390/molecules30030704

AMA Style

Mavratzotis M, Cassel S, De Nicola GR, Montaut S, Rollin P. Synthesis of ω-Methylsulfinyl- and ω-Methylsulfonylalkyl Glucosinolates. Molecules. 2025; 30(3):704. https://doi.org/10.3390/molecules30030704

Chicago/Turabian Style

Mavratzotis, Manolis, Stéphanie Cassel, Gina Rosalinda De Nicola, Sabine Montaut, and Patrick Rollin. 2025. "Synthesis of ω-Methylsulfinyl- and ω-Methylsulfonylalkyl Glucosinolates" Molecules 30, no. 3: 704. https://doi.org/10.3390/molecules30030704

APA Style

Mavratzotis, M., Cassel, S., De Nicola, G. R., Montaut, S., & Rollin, P. (2025). Synthesis of ω-Methylsulfinyl- and ω-Methylsulfonylalkyl Glucosinolates. Molecules, 30(3), 704. https://doi.org/10.3390/molecules30030704

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