Bis disulfides

Williams and Rastetter also accomplished an elegant synthesis of ( )-hyalodendrin (83) in 1980 [39]. Beginning with the sarcosine anhydride-derived enolic aldehyde 78, silyl protection of the enal enabled alkylation of the glycine center with benzyl bromide and thiolation using LDA and monoclinic sulfur a la Schmidt. After protection of the thiol with methylsulfenyl chloride and deprotection of the silyl ether, the enol was sulfenylated with triphenylmethyl chlorodisulfide to afford bis(disulfide) 82 as a 2 1 mixture of diastereomers favoring the anti isomer. Reduction of the disulfides with sodium borohydride and oxidation with KI3 in pyridine afforded ( )-hyalodendrin (83) in 29 % yield (Scheme 9.4). 

Bloxham, D.P., and Cooper, C.K. (1982) Formation of a polymethylene bis(disulfide) inter-subunit crosslink between cys-281 residues in rabbit muscle glyceraldehyde-3-phosphate dehydrogenase using octamethylene bzs-(methane[35]thiosulfonate). Biochemistry 21, 1807. 

Scheme 10 Bis-disulfide Formation with Air Oxygen and Iodine...

Scheme 11 Bis-disulfide Formation with Dimethyl Sulfoxide and Thallium(III) Trifluoroacetate1 071...

Scheme 12 Bis-disulfide Formation with Iodine and Chlorosilane/Sulfoxide1 241...

Scheme 13 Bis-disulfide Formation by Air Oxygen and Dimethyl Sulfoxide/Acid1521...

Scheme 14 Solid-Phase Bis-disulfide Formation with Carbon Tetrachloride and Thallium(III)I1071 Tmb Acm Tmb Acm...

The bis-disulfide bridged human insulin 59 (l.Omg, 0.17pmol) in TFA (0.6mL) was treated with Me-SiCl3 (5 pL 250 equiv) in the presence of PhS(0)Ph (0.7 mg, 20 equiv) at 25 °C for 15 min. NH4F (3 mg) was added to the mixture, and the solvent was removed in under reduced pressure. The residue was dissolved in 50% AcOH (1 mL) and the soln was gel-filtered on Sephadex G-25. The product 42 was further purified by semipreparative HPLC yield 0.6mg (61%) the synthetic human insulin was characterized by amino acid analysis and FAB-MS, it exhibited identical chromatographic and biological properties as a reference compound. 

The formation of a single product from zinc distillation and only one disulfonic acid by oxidation would follow if cassipourine were a bis-(disulfide) with the two halves symmetrically substituted, and a 1,2-structure was envisaged as the most rational. The X-ray analysis of a... 

The diacetal trithiocarbonate (97), on partial reduction, gave the mercaptodithiolane (94). The diacetal trithiocarbonate (95), on prolonged reaction with methyl potassium xanthate, gave a product shown by nuclear magnetic resonance to contain an eight-membered bis(disulfide) ring (103). ... 

Di-Bunte salts have also been used to re-cross-link reduced keratin fibers through a bis-disulfide type of linkage [89,91],... 

The bis(disulfide) moieties contained in 1,2,5,6-tetrathiocanes exhibit interesting reactivity. While eight-membered ring bis(disulfides) are uniquely stable, they rapidly polymerize at elevated temperatures <87JA6825,89T9i>. Compounds (38), (39), and (40) were found to polymerize in < 15 min, when heated to their melting points in the presence of NaSMe <89T9l>. 

The chemistry of 1,2,5,6-tetrathiocanes is complex. Compounds having 1,2-dithiol moieties form cyclic bis(disulfides) in relatively dilute solutions (ca. 1 mM) but polymerize at high concentrations... 

Several bis(disulfide) compounds in this class are formed in low yields or as reaction byproducts. The pyrolysis of diallyl disulfide at 150°C afforded cisjtrans-3,1- and cM/rraMs-3,8-dimethyl-l,2,5,6-tetrathiocane in trace quantities <88JA7813>. Compound (124) (mp 283-285 °C subl.) is formed as... 

Dithiothymidine (98) has been prepared as outlined in Scheme 12. The dimesylate 97 could be converted into the rAreo-bis(disulfide) 99, but all attempts to isolate the rAreo-dithiol led to the formation of the cyclic disulfide 100, even though the dithiol could be trapped as an isopropylidene derivative. ... 

Other Heterocycles. Reaction of 2,2 -biindolyl in dichloro-methane with 2 equiv Scm-Cl generates a 3,3 -bis(methoxycar-bonylsulfenyl) derivative that, upon heating with base and exposure to air, produces a highly insoluble bis-disulfide dimer (eq 20). ... 

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