Isonitrile derivatives

Cyclopeptide alkaloids 91-96 were synthesized in analogy to 90 (Table 1). Isonitrile derivatives of 85 could be used in the same way. 

One of the pioneer works in the synthesis of DKPs through MCRs was reported by Hulme and coworkers in a three-step solution phase protocol based on UDC [33, 34]. They have obtained a series of different DKPs by reacting Armstrong s convertible isocyanide with aldehydes, M-Boc-protected amino acids as bifunctional acid component containing a protected internal amino nucleophile, and amines in methanol at room temperature. After Ugi-reaction, the isonitrile-derived amide is activated with acid (UAC) and allows cyclization to the DKP with the... 

Schrauzer has shown that compounds derived from molyb-denum(V)-cysteine derivatives also catalyze the reduction of dinitrogen. Subsidiary experiments confirm that the active species contain molybdenumdV) rather than molybdenum Ill), the latter tending to lead to the production of dihydrogen (279). Molybdenum isonitrile derivatives can also lead to dinitrogen-reduction catalysis (252). These systems are very difficult to analyze, and they often work best at low molybdenum concentrations (<10 3 M). The intermediates cannot be isolated or detected directly. Their nature must be inferred on the basis of circumstantial evidence, and this is sometimes difficult to interpret. 

There have been no successful syntheses using carbonylate anions with halide or pseudohalide substituents. Indeed, it is known that cyanide-containing anions react with organosilicon halides to give isonitrile derivatives (50), e.g.,... 

In 1988 Lalor reported the synthesis and spectroscopic characterization of some new poly(benzo-triazolyl)borate salts (Scheme 8).180 The regiospecifity of the synthesis of I I B( Btz)4 differs from that of pyrazole/BH4 reaction in that B—N bond formation takes place in a manner that maximizes steric crowding at boron (i.e., at the triazole N(l) atoms). In 1989 Shiu describes some new metal carbonyls of HB(Btz)3.181 The synthesis and spectroscopic characterization of some first-row transition metal complexes was reported by Cecchi,182 whereas Hill described some new Rh183 and Ru184 carbonyl and isonitrile complexes. The formation of isonitrile derivatives was proposed to proceed through an associative mechanism involving an intermediate complex... 

ABSTRACT A series of about 70 secondary metabolites produced by marine organisms have been grouped into three structural types and discussed in terms of their reported antimalarial activities. The major groups of metabolites include isonitrile derivatives, alkaloids and cycloperoxide derivatives. Structure-activity relationships and, when applicable, mechanisms of action of the isolated molecules, have been discussed. The following discussion evidences that antimalarial marine molecules can efficiently integrate the panel of lead compounds isolated from terrestrial sources with new chemical backbones and, sometimes, with typically marine functional groups (as isonitriles). 

On the other hand, the activity of the neoamphilectane derivative 21 (IC50 = D6, 90 ng/mL W2, 29.7 ng/mL) is considerably higher than that of compound 18, indicating that the carbon skeleton can modulate the antiplasmodial activity of isonitrile derivatives. For example, in some cases, unfavourable steric interactions may be important. 

Interaction of marine isonitriles derivatives with heme was shown to inhibit the transformation of heme into / -hematin and then hemozoin, a polymer produced by Plasmodium in order to neutralize the toxic (detergent-like) free heme produced in the food vacuole. In addition, isonitriles were shown to prevent both the peroxidative and glutathione-mediated destruction of heme under conditions that mimic the environment within the malaria parasite. In summary, isonitriles, similarly to quinoline antimalarials [38], exert their antiplasmodial activity by preventing heme detoxification. 

The Pictet-Spengler reaction has been combined with Ugi multi-component chemistry to construct a number of polycyclic indoles. Isonitrile derivatives prepared from tryptamine (or methyl tryptophanate), a carboxylic acid and formaldehyde condense with aminoacetaldehyde diethyl acetal. A few examples employed substituted aldehydes [352]. 

Addition of X2 (X = Br, I) to Tp W(CO)2(=CNREt) (R = Me, Et) results in the dihalo complexes Tp WX2(=CNREt). Treatment of these with Na/Hg in the presence of CNEt affords the isonitrile derivatives Tp W(CNEt)2(sCNREt) and these alkylate (Et30 ) on an isonitrile ligand to form the... 

The complexes of Y, Nd, Tb, Ho and Yb tricyclopentadienides with cyclohexylisonitrile, like THE solvates, are very oxygen- and moisture-sensitive [159]. Their hydrolysis leads to the metal hydroxide, cyclopentadiene and cyclohexylisonitrile. However, they are rather thermostable. The decomposition of the complexes in N2 atmosphere is observed on heating up to 240 C, that exceeds by 100-120 C their melting temperature. Unlike THF-solvates, isonitrile derivatives easily dissolve in ether and benzene [159, 161]. 

These derivatives are interesting insofar as this category of nitrogen terpenes, which possess functional isothiocyanate and N-formylamino groups, is common in sponges of the family Axinellidae (Hahchondrida). The only notable difference is that Axinellidae almost always contain the corresponding isonitrile derivative, whereas this does not seem to have been identified so far in any member of the Lithistida. 

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