Zwiebelanes: novel biologically active 2,3-dimethyl-5,6-dithiabicyclo[2.1.1]hexane 5-oxides from onion

Bayer, Thomas; Wagner, Hildebert; Block, Eric; Grisoni, Serge; Zhao, Shuying; Neszmélyi, András

doi:10.1021/ja00190a064

Cited by 66 publications

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“…Allicin would then be transformed to 1-propenyl-1-propene-thiosulfinate and then become converted to 2,3-dimethylbutanedithial-1-oxide by [3,3]-sigmatropic rearrangement. 21) Next, this compound may be ring-closed to a dimethylthiophene-sulfenic acid adduct, which would be further attached by 1-propenesulfenic acid (a) derived from allicin to finally produce garlicnins B 1 -B 4 as shown in Chart 1.…”

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confidence: 99%

Garlicnins B1, C1, and D, from the Fraction Regulating Macrophage Activation of Allium sativum

et al. 2012

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Several novel sulfides from acetone extracts of bulbs of garlic (Allium sativum L.), were identified and investigated. These were named garlicnins B 1 (1), C 1 (2), and D (3), and they were found to have the ability to control macrophage activation. Garlicnins B 1 (1) and C 1 (2) possess a new skeleton of cyclic sulfoxide and their structures of garlicnins B 1 (1) and C 1 (2) were characterized as 3,4-dimethyltetrahydrothiophene-Soxide derivatives carrying the substitutions of a propenyl and a sulfenic acid, and an allyldithiine and a 1-propene-sulfenic acid (a), respectively. The mechanism of the proposed production of these compounds is discussed. Garlicnin D (3), dithiine-type, was estimated to be derived by addition of (a) allyl thiosulfenic acid (b) derived from allicin. The identification of these novel sufoxides from onion and garlic accumulates a great deal of new chemistry to the Allium sulfide field, and future pharmacological investigations aid the development of natural, healthy foods and anti-cancer agents that could potentially prevent or combat disease.Key words Allium sativum; sulfoxide; garlicnin B 1 ; garlicnin C 1 ; garlicnin D; macrophage activation Garlic, Allium sativum L. (Liliaceae) is at the top of the National Cancer Institute's list of designer foods that prevent cancer. The various biological activities of garlic are generally classified into two cases, cardiovascular disease prevention and cancer prevention. For the former, activities include the inhibition of cholesterol synthesis, platelet aggregation, and arterial smooth muscle cell proliferation inhibition as well as having anti-inflammatory, anti-oxidant, and hydrogen sulfide-mediated vasodilatory effects. Effects on carcinogen metabolism (enhanced cellular glutathione synthesis induced cell cycle arrest and apoptosis) and prevention of Helicobacter pylori infection, gastric cancer, and colorectal cancer make up the latter category.1-3) The chemistry of garlic sulfides is summarized in a text book editted by Block. 3,4) In previous work, we isolated a novel, stable sulfide, 3,4-dimethyl-5-(1-propenyl)-tetrahydrothiophene-2-sulfoxide-S-oxide, from the acetone extract of Allium cepa L. which was found to inhibit macrophage activation. We named this onionin A. 5)Here, sulfur-containing substances from an acetone-soluble extract of A. sativum L. have been isolated and characterized to aid the development of natural, healthy foods that potentially prevent and combat disease, in particular tumors.Chinese garlic (1061 g) was roughly chopped and blended in a mixer along with acetone. Subsequently, the mixture was soaked in acetone for 3 d at room temperature. The filtrate was evaporated at 40°C in vacuo to obtain a residue (26.1 g), which was then subjected to polystyrene gel column chromatography (Diaion HP-20). It was first eluted with water, then with methanol (residue after evaporation: 5.90 g), and finally with acetone (the residue after evaporation: 0.32 g). Part of the methanolic eluate (3.0 g) was partitioned between ethyl ace...

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Garlicnins B1, C1, and D, from the Fraction Regulating Macrophage Activation of Allium sativum

et al. 2012

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“…In fact, the bulk of the plethora of biological activities reported for Allium crops such as garlic and onion have been ascribed to the organosulfur small molecule derivatives of precursor S-substituted Cys sulfoxides, most notably the thiosulfinates and complex compounds that are formed from them that appear further downstream, such as di-, tri-, and polysulfides, cepaenes, and the aforementioned zwiebelanes. These molecules are reported to exhibit cardiovascular effects, antimicrobial activity, and anticancer activity (Bayer et al, 1989;Dorsch et al, 1990;Block, 1992;Iranshahi et al, 2008;Block, 2010). We have shown that petivericin and other thiosulfinates produced from P. alliacea S-substituted Cys sulfoxide precursors also exhibit significant antibacterial and antifungal activity (Kim et al, 2006).…”

Section: Discussionmentioning

confidence: 99%

Discovery and Characterization of a Novel Lachrymatory Factor Synthase inPetiveria alliaceaand Its Influence on Alliinase-Mediated Formation of Biologically Active Organosulfur Compounds

Musah

Kubec

2009

Plant Physiology

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A novel lachrymatory factor synthase (LFS) was isolated and purified from the roots of the Amazonian medicinal plant Petiveria alliacea. The enzyme is a heterotetrameric glycoprotein comprised of two a-subunits (68.8 kD each), one g-subunit (22.5 kD), and one d-subunit (11.9 kD). The two a-subunits are glycosylated and connected by a disulfide bridge. The LFS has an isoelectric point of 5.2. It catalyzes the formation of a sulfine lachrymator, (Z)-phenylmethanethial S-oxide, only in the presence of P. alliacea alliinase and its natural substrate, S-benzyl-L-cysteine sulfoxide (petiveriin). Depending on its concentration relative to that of P. alliacea alliinase, the LFS sequesters, to varying degrees, the sulfenic acid intermediate formed by alliinase-mediated breakdown of petiveriin. At LFS:alliinase of 5:1, LFS sequesters all of the sulfenic acid formed by alliinase action on petiveriin, and converts it entirely to (Z)-phenylmethanethial S-oxide. However, starting at LFS:alliinase of 5:2, the LFS is unable to sequester all of the sulfenic acid produced by the alliinase, with the result that sulfenic acid that escapes the action of the LFS condenses with loss of water to form S-benzyl phenylmethanethiosulfinate (petivericin). The results show that the LFS and alliinase function in tandem, with the alliinase furnishing the sulfenic acid substrate on which the LFS acts. The results also show that the LFS modulates the formation of biologically active thiosulfinates that are downstream of the alliinase in a manner dependent upon the relative concentrations of the LFS and the alliinase. These observations suggest that manipulation of LFS-to-alliinase ratios in plants displaying this system may provide a means by which to rationally modify organosulfur small molecule profiles to obtain desired flavor and/or odor signatures, or increase the presence of desirable biologically active small molecules.

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“…30) Next, the generated compound was ring-closed to form a thiophene derivative that was attached with 1-propenesulfenic acid or/and allyl thiosulfenic acid derived from allicin to finally produce the thiolane-type sulfides, onionins A 1 , A 2 , and A 3 as illustrated in Chart 1.…”

Section: Structures Of Isolated Sulfides From Onion Welshmentioning

confidence: 99%

Antitumor Allium Sulfides

et al. 2017

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We examined the sulfides in onion (Allium cepa L.), Welsh onion (A. fistulosum L.), and garlic (A. sativum L.), and obtained three new thiolane-type sulfides (onionins A 1 -A 3 ) from onion; two new thiabicyclic-type sulfides (welsonins A 1 , A 2 ), together with onionins A 1 -A 3 , from Welsh onion; and six new acyclic-type sulfides (garlicnins L-1-L-4, E, and F), ten new thiolane-type sulfides (garlicnins A, B 1 -B 4 , C 1 -C 3 , K 1 , and K 2 ), and three new atypical cyclic-type sulfides (garlicnins G, I, and J) from garlic. Acetone extracts showed the potential of these sulfides in inhibiting the polarization of M2 activated macrophages that are capable of suppressing tumor-cell proliferation. The effect of the thiolane-type sulfide of a major component, onionin A 1 , on tumor progression and metastasis in both osteosarcoma and ovarian cancer-bearing mouse models was then examined. Tumor proliferation was depressed, and tumor metastasis was controlled by regulating macrophage activation. These results showed that onionin A 1 is an effective agent for controlling tumors in both in vitro and in vivo models, and that the antitumor effects observed in vivo are likely caused by reversing the antitumor immune system. Activation of the antitumor immune system by onionin A 1 might be an effective adjuvant therapy for patients with osteosarcoma, ovarian cancer and other malignant tumors. Based on these findings, pharmacological investigations will be conducted in the future to develop natural and healthy foods and anti-cancer agents that can prevent or combat disease.

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Zwiebelanes: novel biologically active 2,3-dimethyl-5,6-dithiabicyclo[2.1.1]hexane 5-oxides from onion

Cited by 66 publications

References 0 publications

Garlicnins B<sub>1</sub>, C<sub>1</sub>, and D, from the Fraction Regulating Macrophage Activation of <i>Allium sativum</i>

Garlicnins B<sub>1</sub>, C<sub>1</sub>, and D, from the Fraction Regulating Macrophage Activation of <i>Allium sativum</i>

Discovery and Characterization of a Novel Lachrymatory Factor Synthase inPetiveria alliaceaand Its Influence on Alliinase-Mediated Formation of Biologically Active Organosulfur Compounds

Antitumor <i>Allium</i> Sulfides

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