1.3- Dithiolane

2-Dithiolanes can be viewed as cyclic disulfanes. A C-S-S-C dihedral angle of 26.6° results from the elctronic interaction between the S-atoms. For this reason, a considerable ring strain is caused by the widening of the bond angles, as can be deduced from the Newman projection formula. The strain enthalpy was found to be 67 kJ mol-i. 

2-Dithiolanes are very reactive because of ring strain. 1,2-Dithiolane polymerizes at room temperature. Nevertheless, about 20 1,2-dithiolanes are found in nature. Among them, a-lipoic acid (6,8-disul-fanyloctanoic acid) is of great biological importance. The crystalline compound was isolated for the first time in 1951 from the liver of cattle. 

Flies are killed upon contact with the marine worm Lumbriconereis. Nereistoxin 1 was identified as the active substance in this worm, and its constitution determined as 4-dimethylamino-l,2-dithiolane. 

Consequently, structural analogs were synthesized and introduced as insecticides, for example, thiocyclam (2). 

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The reaction of 1,2-dithiolanes with 2- and 4-picolyllithium has been examined <96PS(112)101> and the reactions of thioanhydrides such as 94 with both thiols <95JOC3964> and amines <96TL5337> have been reported. Treatment of 1,2-dithiolium salts with lithium or thallium cyclopentadienide results in formation of a variety of bi-, tri- and tetracyclic products <96LA109>. Reaction of 95 with trimethyl phosphite gives some of the desired coupling product but also the phosphonates 96 <96PS(109)557>. 

Pyridyl-l,3-dithianes (50) result from the reaction of picolyl lithium reagents with 1,2-dithiolanes in the presence of HMPT. An initial ring opening is followed by reaction at the carbanion site with a second mole of dithiolane <96PS(112)101>. 

A more complex structure is that of leinamycin 45 (Scheme 15), a material with potent cytotoxic and antitumor properties, isolated from a Streptomyces sp. A 1,2 dithiolane-3-one ring is spiro fused to a complex macrolactam96 (and references therein). Leinamycin has the remarkable ability to cleave DNA. In brief, leinamycin reacts with a thiol and, after a profound rearrangement, forms an episulfonium ion. This ion alkylates the N7 position of guanosine residues in double stranded DNA an unstable adduct is depurinated by hydrolysis of the glycosidic bond between the alkylated base and a deoxyribose residue. Some structurally less complex l,2-dithiolane-3-one 1-oxides have a similar DNA cleaving ability.97... 

The formation of S-oxides has also been observed when oxidizing a variety of 5-substituted 2-tert-butyl-l,3-dithianes in wet acetonitrile. In an undivided cell, 4-substituted 1,2-dithiolane-l-oxides were oblained (Scheme 25) [113]. A coupled cathodic process, in this case, was the reduction of protons formed in the anodic reaction. 

Scheme 25 Conversion of 1,3-dithianes into 1,2-dithiolane-l-oxides.

The oxidation of dithianes (Scheme 13) leads to a dicationic species that reacts with water affording aldehydes or ketones and 1,2-dithiolane, which undergoes further oxidation to the sulfoxide (20-74% yields) [18]. 

As previously illustrated in Scheme 13, the anodic oxidation of dithianes involves a ring contraction affording 1,2-dithiolane [18]. 

Animal Sources. The marine annelid worm Lumbrineris hetero-poda produces an insect toxin nereistoxin, 24, 4-N,N-dimethyl-amino-1,2-dithiolane (5 ). The mink MusteXa vison) affords 2,2-dimethylthietane, 14, and 3,3-dimethy1-1,2-dithiolane, 25 (28,63, 64), the ferret Musteta putoris) secretes 14, 25, cis- and trans-2,3-dimethylthietane, 2-propyl- and 2-pentyl-thietane, cis and trans-3,4-dimethyl-l,2-dithiolane, and 3-propyl-l,2-dithiolane (65), and the stoat (Mustela erminea) contains 2-ethyl-, 2-propyl-, and 2-pentyl-thietane, and 3-ethyl- and 3-propyl-l,2-dithiolane in its anal gland (5, ). These several thiaheterocycles from mustela species probably function as scent markers. 

Similar ring expansion reactions 1,2-dithiolanes were observed when thi-etanes, after base [(Et)2NH-DMFA]-catalyzed ring opening, were heated with sulfur. - ... 

Die Reduktion von Azido-Verbindungen zu primaren Aminen nach alteren, jedoch auch heute noch gangigen Verfahren ist in Bd.XI/1, S. 539-545 besprochen. Uber neuere Ver-fahren und neuere Beispiele informiert die Auswahl, die in Tab. 104 (S. 960) zusammen-gestellt ist. Eines der dort aufgefuhrten, selektiv wirkenden Reduktionsmittel ist 1,3-Pro-pandithiol, das bei der Reduktion der Azido-Verbindung zu 1,2-Dithiolan cyclodehydriert... 

A limited number of examples have been published of the insertion of sulfur into thietane rings giving 1,2-dithiolanes such as (45) (76BCJ2491) and (46) (70TL441, 71CPB1022). 

Fluorodcsulfurizations of thiols,311 phenyl thioglycosides,290 1,2-dithiolans.312 aromatic dithiocarboxylic acids,399 or orthothioesters313 in hydrogen fluoride systems with N-chloro-or N-bromosuccinimide as a coagcnt are facile methods for the generation of monofluorides, gem-difluorides, and trifluoromethyl derivatives, e.g. formation of 11,311 12,312 13,313 and... 

Nereistoxin (44) is a 1,2-dithiolane neurotoxic derivative isolated from a marine annelid, Lumbriconercis heteropoda Marenz.61 Nereistoxin served as a model for the commercial insecticide Padan. 

The sulfur in 1,2-dithiolanes is nucleophilic and is alkylated easily to form 1,2-dithiolanium ions (465—>466) (85JA2807, 85PS(23)169>. 

A general route to 1,2-dithiolanes (53) involves oxidation of the 1,3-dithiol (52) with hydrogen peroxide at 75°C in acetic acid containing potassium iodide. (3-Dithio compounds such as (54) undergo oxidation in acid to the 1,2-dithiolylium salts (55) (76JCS(D)455). 

The tobacco alkaloid nicotine (96) (B-67MI10702) is insecticidal by virtue of its action on the acetylcholine receptor. It was used widely as an aphicide, especially as a fumigant. Another natural product thought to act on the same receptor is the 1,2-dithiolane nereistoxin (97) (B-72MI10703), isolated from the marine annelid Lumbriconereis heteropoda. The active form has been shown to be the ring opened dithiol (98), and the protected form of it, cartap (99), is sold as a rice insecticide. The 1,2,3-trithiane thiocyclam (100) (72SAP7007824) is also active, presumably because of metabolic conversion to (98). 

A number of naturally occurring compounds with a disulfide unit have shown interesting biological activity [28, 29]. Nereistoxin, charatoxin, asparagusic acid, a plant growth inhibitor, and lipoic acid, a key co-factor in the oxidative decarboxylation of pyruvate, are examples taken in the 1,2-dithiolan series. 

AC86 C4M6O2S2 1,2-dithiolane-4-carboxylic acid T5S5TJ DVG EtOH 25 PO buffer - 1.2 7.0 - SME/ - -2 C=1... 

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