Thiosulfinate

File:R-allicin-2D-skeletal.svg

A variety of acyclic and cyclic thiosulfinates are found in plants, or formed when the plants are cut or crushed.

A well-known thiosulfinate is allicin, one of the active ingredients formed when garlic is crushed. Allicin was discovered in 1944 by Chester J. Cavallito and coworkers. Thiosulfinates containing various combinations of the methyl, n-propyl, 1-propenyl, 2-propenyl, n-butyl, 1-butenyl and 2-butenyl groups are formed upon crushing different Allium as well as Brassica species.{{cite journal |last=Kubec|first= R|author2=Cody, RB |author3=Dane, AJ |author4=Musah, RA |author5=Schraml, J |author6=Vattekkatte, A |author7= Block, E |year=2010|title=Applications of DART Mass Spectrometry in Allium Chemistry. (Z)-Butanethial S-Oxide and 1-Butenyl Thiosulfinates and their S-(E)-1-Butenylcysteine S-Oxide Precursor from Allium siculum|journal= J. Agric. Food Chem.|volume= 58|issue= 2|pages= 1121–1128|doi=10.1021/jf903733e |pmid=20047275}}{{cite journal |last=Block|first= E|author2=Dane, AJ |author3=Thomas, S |author4= Cody, RB |year=2010|title=Applications of Direct Analysis in Real Time–Mass Spectrometry (DART-MS) in Allium Chemistry. 2-Propenesulfenic and 2-Propenesulfinic Acids, Diallyl Trisulfane S-Oxide and Other Reactive Sulfur Compounds from Crushed Garlic and Other Alliums|journal=J. Agric. Food Chem. |volume= 58|issue= 8|pages= 4617–4625|doi =10.1021/jf1000106 |pmid=20225897|bibcode= 2010JAFC...58.4617B}}

Zeylanoxides are cyclic thiosulfinates containing the 1,2-dithiolane-1-oxide ring, isolated from the tropical weed Sphenoclea zeylanica. These heterocyclic thiosulfinates are chiral at carbon as well as at sulfur.{{cite journal|last=Hirai |first=N|author2=Sakashita, S |author3=Sano, T |author4=Inoue, T |author5=Ohigashi, H |author6=Premasthira, C |author7=Asakawa, Y |author8=Harada, J |author9= Fujii, Y |title=Allelochemicals of the tropical weed Sphenoclea zeylanica |journal=Phytochemistry|year=2000|volume=55|issue=2|pages=131–140|doi=10.1016/S0031-9422(00)00264-8|pmid=11065289|bibcode=2000PChem..55..131H}}

Crushing the roots of Petiveria alliacea affords the thiosulfinates S-(2-hydroxyethyl) 2-hydroxyethane)thiosulfinate, S-(2-hydroxylethyl) phenylmethanethiosulfinate, S-benzyl 2-hydroxyethane)thiosulfinate and S-benzyl phenylmethanethiosulfinate (petivericin; {{chem2|Ph\sCH2\sS(O)\sS\sCH2\sPh}}, Ph = phenyl).{{cite journal|last=Kubec|first=R|author2=Kim, S |author3=Musah, RA |title=S-Substituted cysteine derivatives and thiosulfinate formation in Petiveria alliacea--Part II|journal=Phytochemistry|year=2002|volume=61|issue=6|pages=675–680|doi=10.1016/S0031-9422(02)00328-X |pmid=12423888|bibcode=2002PChem..61..675K|url=http://www.rabimusah.com/pdfs/Cysteine%20S-Substituted%20Cysteine%20Derivatives_part%202.pdf}} Asparagusic acid S-oxide{{cite journal|last=Yanagawa|first=H|author2=Kato, T |author3=Kitahara, Y |title=Asparagusic acid-S-oxides, new plant growth regulators in etiolated young asparagus shoots|journal=Tetrahedron Letters|year=1973|volume=14|issue=13|pages=1073–1075|doi=10.1016/S0040-4039(01)95907-6}} and brugierol{{cite journal|last=Kato|first=A|author2=Numata M |title=Brugierol and isobrugierol, trans- and cis-1,2-dithiolane-1-oxide, from Brugiera conjugata|journal=Tetrahedron Letters |year=1972 |volume=13 |issue=3|pages=203–206 |doi=10.1016/S0040-4039(01)84280-5}} are other natural 1,2-dithiolane-1-oxides occurring in Asparagus officinalis and Bruguiera conjugata, respectively.

Allicin, S-benzyl phenylmethanethiosulfinate, and related thiosulfinates show radical-trapping antioxidant activity associated with easy formation of sulfenic acids{{cite journal|last=Lynett |first=PT|author2=Butts, K |author3=Vaidya, V |author4=Garretta, GE |author5= Pratt, DA |title=The mechanism of radical-trapping antioxidant activity of plant-derived thiosulfinates|journal=Org. Biomol. Chem.|year=2011|volume=9|issue=9|pages=3320–3330|doi=10.1039/c1ob05192j|pmid=21445384}} The acyclic thiosulfinates from Allium and Brassica species possess antimicrobial, antiparasitic, antitumor and cysteine protease inhibitory activity while the natural 1,2-dithiolane-1-oxides are growth inhibitors. The thiosulfinates from Petiveria also exhibit antimicrobial activity.{{cite journal|last=Kim|first=S|author2=Kubec, R |author3=Musah, RA |title=Antibacterial and antifungal activity of sulfur-containing compounds from Petiveria alliacea|journal=Journal of Ethnopharmacology|year=2006|volume=104|issue=1–2|pages=188–192|doi=10.1016/j.jep.2005.08.072 |url=http://www.rabimusah.com/pdfs/Antibacterial%20and%20Antifungal%20Activity.pdf |pmid=16229980}}

Thiosulfinates feature a S(IV) center linked to a S(II) center, the former being stereogenic. Conversion of simple disulfides to thiosulfinates results in a considerable weakening of the S–S bond from about 47.8 to 28.0 kcal mol⁻¹ for the S-S bond in PhS(O)SPh and from about 63.2 to 39.3 kcal mol⁻¹ for the S-S bond in MeS(O)SMe,{{cite journal | last1 = Block | first1 = E.| last2 = Cotelesage | first2 = J.J.H. | last3 = Dikarev | first3 = E. | last4 = Garosi | first4 = B. | last5 = George | first5 = G.N. | last6 = Musah | first6 = R.A. | last7 = Vogt | first7 = L.I. | last8 = Wei | first8 = Z. | last9 = Zhang | first9 = Y. | year = 2024 | title = Re-examination of the claimed isolation of stable noncyclic 1,2-disulfoxides |journal = Organic Letters | volume = 26| issue = 45 | pages = 9619–9624|doi=10.1021/acs.orglett.4c02849 | doi-access = free | pmid = 39230394| pmc = 11574841}} with the consequence that most thiosulfinates are both unstable and quite reactive. For this reason the mixtures of thiosulfinates from Allium plants can best be separated by HPLC at room temperature rather than by gas chromatography (GC), although GC has been used with some low molecular weight thiosulfinates. Thiosulfinates can be distinguished from sulfoxides by infrared spectroscopy since they have a characteristic S=O band at about 1078 cm⁻¹ compared to 1030–1060 cm⁻¹ in sulfoxides.{{cite book|author=Block E|title=Garlic and Other Alliums: The Lore and the Science|url=https://books.google.com/books?id=6AB89RHV9ucC|publisher=Royal Society of Chemistry|year=2010|isbn=978-0-85404-190-9}}

Synthetic thiosulfinates were first reported in 1947 by Cavallito and coworkers by oxidation of the corresponding disulfides.{{cite journal |last=Small |first=LD |author2=Bailey, JH |author3=Cavallito, CJ |title=Alkyl thiolsulfinates |journal=J. Am. Chem. Soc.|year=1947|volume=69|issue=7 |pages=1710–1713|doi=10.1021/ja01199a040|pmid=20251406 |bibcode=1947JAChS..69.1710S}}

One example of a moderately stable thiosulfinate is the tert-butyl derivative, {{chem2|(CH3)3CS(O)SC(CH3)3}}. This thiosulfinate can be obtained in optical purity by catalytic asymmetric oxidation of di-tert-butyl disulfide with hydrogen peroxide.{{cite journal|last=Weix |first= DJ |author2=Ellman, JA |title=(RS)-(+)-2-Methyl-2-Propanesulfinamide [tert-Butanesulfinamide] |journal=Organic Syntheses |year=2005 |volume=82 |pages=157 | doi=10.1002/0471264229.os082.24}} Upon heating, {{chem2|(CH3)3CS(O)SC(CH3)3}} decomposes into tert-butanethiosulfoxylic acid {{chem2|(CH3)3CSSOH}}) as shown by trapping studies.{{cite journal|last=Block |first=E |title=The Chemistry of Alkyl Thiosulfinate Esters. III. tert-Butanethiosulfoxylic Acid|journal=J. Am. Chem. Soc. |year=1972 |volume=94 |issue=2 |pages=644–645 |doi=10.1021/ja00757a060|bibcode=1972JAChS..94..644B}}

In a similar manner racemic methyl methanethiosulfinate ({{chem2|CH3S(O)SCH3}}) can be obtained by peracetic acid oxidation of dimethyl disulfide.{{cite journal|last=Moore |first=TL |author2=O'Connor, DE |title=The Reaction of Methanesulfenyl Chloride with Alkoxides and Alcohols. Preparation of Aliphatic Sulfenate and Sulfinate Esters |journal=J. Org. Chem. |year=1966 |volume=31 |issue=11 |pages=3587–3592 |doi=10.1021/jo01349a027}} Methyl methanethiosulfinate decomposes thermally giving methanesulfenic acid ({{chem2|CH3SOH}}), the simplest sulfenic acid, as well as thioformaldehyde ({{chem2|CH2\dS}}). Methyl methanethiosulfinate can also disproportionate to a 1:1 mixture of dimethyl disulfide and methyl methanethiosulfonate ({{chem2|CH3SO2SCH3}}) and rearrange via a Pummerer rearrangement to {{chem2|CH3S(O)CH2SSCH3}}.{{cite journal|last=Block |first=E|author2=O'Connor, J|title=The Chemistry of Alkyl Thiosulfinate Esters. VI. Preparation and Spectral Studies|journal=J. Am. Chem. Soc. |year=1974|volume=96|issue=12| pages=3921–3929|doi=10.1021/ja00819a033|bibcode=1974JAChS..96.3921B}}{{cite journal|last=Block |first=E|author2=O'Connor, J|title=The Chemistry of Alkyl Thiosulfinate Esters. VII. Mechanistic Studies and Synthetic Applications |journal=J. Am. Chem. Soc. |year=1974|volume=96|issue=12| pages=3929–3944 |doi=10.1021/ja00819a034|bibcode=1974JAChS..96.3929B}}

An unusual three-membered ring thiosulfinate (a dithiirane 1-oxide) has been prepared through rearrangement of a 1,3-dithietane.{{cite journal|last=Ishii|first=A|author2=Akazawa, T |author3=Ding, MX |author4=Honjo, T |author5=Nakayama, J |author6=Hoshino, M |author7= Shiro, M |title=First isolable dithiiranes: 3-(1,1,3,3-tetramethyl-4-oxo-4-phenylbutyl)-3-phenyldithiirane 1-oxides |journal=J. Am. Chem. Soc. |year=1993|volume=115|issue=11|pages=4914–4915 |doi=10.1021/ja00064a072|bibcode=1993JAChS.115.4914I}} A related compound, 3-(9-triptycyl)dithiirane-1-oxide, was prepared by the reaction of (9-triptycyl)diazomethane and {{chem2|S8O|link=S8O}}. The X-ray structure of the dithiirane-1-oxide reveals a significantly lengthened sulfur-sulfur bond (211.9(3)pm).{{cite journal|last=Ishii|first=A|author2=Kawai, T |author3=Noji, M |author4= Nakayama, J |title=Synthesis and reactions of a monosubstituted dithiirane 1-oxide, 3-(9-triptycyl)dithiirane 1-oxide |journal= Tetrahedron |year=2005|volume=61|issue=28|pages=6693–6699 |doi=10.1016/j.tet.2005.05.017}}

Thiosulfinates have also been invoked as intermediates in the oxidation of thiols to sulfonic acids.

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Category:Sulfur oxyanions