Thiocyanate-derived functionally

Garson, M. J., Simpson, J. S., Flowers, A. E., and Dumdei, E. J., Cyanide and thiocyanate derived functionality in marine organisms-Structures, biosynthesis and ecology, in Bioactive Natural Products (Part B), Vol. 21, Rahman, A., Ed., Elsevier, Amsterdam, 2000, 329. 

CYANIDE AND THIOCYANATE-DERIVED FUNCTIONALITY IN MARINE ORGANISMS -STRUCTURES, BIOSYNTHESIS AND ECOLOGY... 

The conversion of functionalized arenes as represented by the general formula 97, into isothiazolium compounds (99) has been achieved by the sequence shown in Scheme 117.180 From a synthetic viewpoint, transformation of cyclopalladated products into thiocyanate derivatives is more efficiently achieved using monomeric dithiocarbamato complexes (98) rather than dimeric compounds. The generation of analogous dithiolylium perchlorates by a related procedure is described later (see Section IV,H). 

The combination of (diacetoxyiodo)benzene and thiocyanate anion in a polar, protic, non-nucleophilic solvent has been used for the oxidative functionalization of alkenes 538 to acetoxy thiocyanate derivatives 539 with anfi-stereoselectivity and with good regioselectivity (Scheme 3.211) [597]. 

Five compounds (TABLE 5 FIGURE 4) exhibited lethality or sickness in at least one test at a test concentration one-tenth or less below that predicted by equations 2 or 3. Two of these (45,47) are thiocyanate derivatives, which as a class are known to possess special biological activity (Reid 1966 Wilcoxon and McCallen 1935). The thiocyanate functional group is also known to be a chemically reactive moiety (Reid 1966 Bacon 1961). Thiocyanates can react as electrophiles by nucleophilic attack at either the carbon or sulphur atom (SCHEME 1). In the latter case, cyanide would be released as a chemical leaving group. Hermans et al. (1985) has demonstrated that the acute fish lethality of various nonelectrolyte electrophilic compounds correlates poorly with log P (equation 8). 

Attempted selective displacement (96) of the primary tosylate function in 34 with sodium iodide in refluxing 2-butanone led to the 6-deoxy-6-iodo derivative 35 in 32% yield only, while the di-iodo derivative 36 was formed in 45% yield. These results are to be compared with those reported by Owen and Ragg (85) who observed no reaction with either potassium thiolacetate or potassium thiocyanate in the corresponding / -series. 

Aminodebromination of 4-bromo-l//-3-benzazepin-2-amine (25) with triethylamine occurs readily and results in formation of the quaternary salt 26 (see also Section 3.2.1.5.6.), whereas attempts to effect nucleophilic substitution of bromide with primary or secondary amines gives only tarry mixtures.41 The bromo group is also resistant to displacement by azide and benz-cncthiolate but undergoes substitution with thiocyanate ion in hot dimethylformamide to give the 4-thiocyanato derivative 27 rather than the thiourea by addition at the amine function. 

Pyridine derivatives with additional donor functions and sterically demanding substituents have been used with the intention of producing complexes of Cd (and of other metals) with low coordination number one of these ligands is the tridentate, planar-bonding 2,6-bis[(2,6-dimethyl-phenylimino)methyl] pyridine (pydim a Schiff base derived from 2,6-pyridine dialdehyde), which with Cd(BF4)2 and thiocyanate gives a dinuclear complex [(pydim)Cd(/x-NCS-S,N)]2(BF4)2 with N-dominated coordination sphere.191 As centrosymmetric Plijc, Z= 2), the complex has an antiparallel /x-1,3 NCS double bridge with Cd—N and Cd—S bonds (224.6 pm and 255.5 pm, respectively) the Cd—N(py) bond is clearly shorter than the Cd—N(imino) bonds (225.6 pm and 245.0 pm,... 

Although marine organisms produce a large number of isocyanates, isothiocyanates, and formamides, the corresponding thiocyanates have rarely been encountered. Indeed, the thiocyanate functionality has only been found in six sesquiterpenes (263-268), in four tricyclic quinoline alkaloids (271-274), and in psamaplin B (172) (included in the bromotyrosine derivatives discussed in the disulfide/polysulfide section). They have been found in marine sponges, as well as in nudibranches and tunicates. 

In neutral and slightly alkaline media, MPO-compound I can react directly with iodides, bromides, chlorides (K16), thiocyanates, Al-acetylmethionine, cysteine, pyridine nucleotides (S20), and phenols (K16), including tyrosine (H14) and thyroid hormones. Some of these reactions have certain biological importance. In extensive studies, Klebanoff el al. investigated the potential function of MPO as an iodide-oxidizing enzyme (K16). It was found that iodide is rapidly oxidized, forming a bactericidal derivative which produces a fall in the number of viable Escherichia coli 10 times more effectively than bromide and 100 times more effectively than chloride, if used as MPO substrates. Extremely low concentrations of iodides and bromides in leukocytes and blood plasma, however, seem to limit the importance of iodide oxidation in bacteria killing mechanisms. 

Ammonium thiocyanate annulates chioromethyl and ring-nitrogen functions to a thiazole ring on warming in methanol. Under mild conditions, the intermediate thiocyanatomethyl derivative may be isolated. 

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