Activation of isonitrile

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. 

An elegant method for the preparation of some cyclopropenone imines reported by Krebs118 is the (1 + 2) cycloaddition of isonitriles (as divalent carbon species) to activated triple bond of ynamines and certain cycloalkynes, e.g. ... 

Convertible isocyanide reagent 66 allows a mild and chemoselective in situ post-Ugi activation of the isonitrile bom amide with simultaneous deprotection of the nucleophilic amine, that is, liberation and activation of two Ugi-reactive groups, if desired also under subsequent lactam formation [33]. Another recently introduced convertible isocyanide, l-isocyano-2-(2,2-dimethoxyethyl)-benzene 73, was shown effective by Rhoden et al. In the course of this short sequence, a hydrolytically labile W-acylindole 78 is formed, which is displaced intramolecularly by the amine portion of the former Boc-protected amino acid 75 (Scheme 13). 

Recently, a combination of the UAC and UDC protocols was reported by Wessjohann s group [40]. In this work, the acid-activated, well-behaved 1-iso-cyano-2-(2,2-dimethoxyethyl)-benzene was employed as convertible isocyanide in an Ugi-4CR [41]. The advantage of this one-pot procedure is the in situ deprotection of the W-protected amino acid along with the simultaneous activation of the isonitrile-bom carboxylate, enabling the nucleophilic attack of the free amine... 

An interesting route to 98 was suggested by Cramer et al. " cyclization of isonitrile 110 could lead to 98 in a rearrangement analogous to the Bergman cyclization. The activation enthalpy for the only slightly exothermic reaction was estimated at 18 kcal/mol. However, this novel access to m-arynes could not be realized experimentally so far. 

Reactions of arylazosulfones (52) with conjugate bases (53) and (54) of active-methylene isonitriles in DMSO give 1-arylimidazoles (55) and (56), respectively.50... 

Becher PG, Keller S, Jung G, Siissmuth RD, Jiittner F (2007) Insecticidal Activity of 12-epi-Hapalindole J Isonitrile. Phytochemistry 68 2493... 

Wright AD, Wang H, Gurrath M, Kdnig GM, Kocak G, Neumann G, Loria P, Foley M, Tilley L (2001) Inhibition of Heme Detoxification Processes Underlies the Antimalarial Activity of Terpene Isonitrile Compounds from Marine Sponges. J Med Chem 44 873... 

A related reaction is the addition of isonitriles 75 to aldehydes 1 (the Passerini reaction). Denmark has demonstrated that SiCU, upon activation by a chiral Lewis base, which increased the Lewis acidity of the silicon (vide supra Scheme 7.14), can mediate this reaction to produce a-hydroxy amides 77 after aqueous work-up (Scheme 7.16). Phosphoramide 60 was employed as the chiral Lewis-basic catalyst [74]. Modification of the procedure for hydrolysis of 76 gives rise to the corresponding methyl ester (rather than the amide 77) [74]. (For experimental details see Chapter 14.5.5). 

Although the [2 H- l]cycloaddition of isonitriles to the activated triple bond of ynamines and certain cycloalkynes provides a useful route to some cyclopropenimines, the equivalent cycloreversion process is of minor significance in the thermolysis of these compounds dimerization and ring-cleavage processes predominate The photo-... 

Isonitrile ligands on palladium induce the activation of Si-Si bonds very efficiently. Thus, not only a four-membered disilane 10b, five- (14) and six-mem-bered disilanes (15,16) furnish the corresponding cyclic bis(organosilyl)Pd(II) complexes 17-20 quantitatively in the reactions with bis(tert-alkyl isonitrile) palladium(O) (Scheme 1) [20]. 

In the insertion reactions, isonitriles may serve as effective ligands on palladium ) for the activation of Si-Si bonds and, at the same time, they are involved as reactant. In contrast, ferf-alkyl isonitriles, which do not insert into Si-Si bonds at all, can exclusively serve as spectator ligands for highly effective activation of Si-Si bonds [46]. 

In principle, the sharing of the same mechanism of action of chloroquine could be a weak point for isonitrile antimalarials indeed, in this case, cross-resistance phenomena could be stimulated. However, the remarkable selective activity of axisonitrile-3 on chloroquine-resistant strains (see before) encourages further studies. 

Murahashi described a new pyrrole synthesis involving a rhodium complex-catalyzed reaction of isonitriles (e.g., 3) with 13-dicarbonyl compounds 4 to afford the pyrroles 5 <01OL421>. This process is believed to proceed by chemoselective activation of the a-C-H bond of the isonitrile even in the presence of the more acidic dicarbonyl derivative. 

---