Isonitriles, natural

Isocorypalmine see protoberberine alkaloids. Isocyanides (isonitriles, natural). 

Isonitriles are stable, often naturally occurring, compounds that contain a divalent carbon. An example is axisonitrile-3, which can be isolated from a species of sponge and possesses anti-malarial activity. Write a resonance form for axisonitrile-3 that satisfies the octet rule. Don t forget to include formal charges. 

The matter was settled in 1994 in back-to-back communications by Gould [12] and Dmitrienko [13]. Gould showed that treatment of natural prekinamycin with dirhodium tetraacetate in methanol yielded the fluorene 16 (Scheme 3.1). The vinyl proton formed in this reaction (H-l) provided a critical spectroscopic handle and allowed unambiguous determination of the carbocyclic structure, excluding the presence of an indole heterocycle. In parallel, his research group obtained a high-quality crystal structure of a kinamycin derivative. The refined data set was shown to best accommodate a diazo rather than cyanamide (or isonitrile) function. 

Naturally occurring marine isonitriles are either sesquiterpenes or diterpenes with one, two, or three isocyano (or isocyano-related) functions. As mentioned previously, it usually is the same carbon that bears the -NC, -NCS, or -NHCHO function. Commonly encountered in sesqui- and diterpenes are... 

Further examination of the extracts of A. cannabina revealed axisonitrile-4 (7), axisothiocyanate-4 (8) and axamide-4 (9) [33], A vinylic isonitrile function was supported by H NMR signals at <51.67 and 1.89, which were assigned to the two isopropylidene methyls of 7. Difficulty in isolating the natural product 9 was circumvented, when isonitrile 7 was transformed to 9, mp 81-84 °C, by acetic acid in anhydrous ether. The absolute configurations of both axanes 1 and 7 and their analogs were later established [31] by studies including X-ray diffraction of the p-bromoaniline derivative of 2 and by CD data of ( + )-10-methyldecalone-l obtained from ozonolysis of the reduction (Na/NH3) product of 1 [1]. 

Reviews of the syntheses of marine natural products, including marine isonitriles, have appeared recently [72]. After the early synthetic challenges of the tricyclic 9-isocyanopupukeanane (76) [73, 74] and 2-isocyanopupukeanane (78) [75] were met in 1979, additional syntheses of marine isonitriles were reported during 1986-1991. These were ( )-7,20-diisocyanoadociane (95) [63], ( )-axisonitrile-1 (1) and ( )-axamide-l (3) [76], the axisonitrile-4 triad (7-9) [78], and ( )-8,15-diisocyano-ll(20)-amphilectene (96) [79], and theonellin isocyanide (85) [80],... 

The structural diversity of natural products with antimalarial activity from marine and freshwater sources are stunning, ranging from isonitrile-containing derivatives to depsipeptides through peroxides and alkaloids. 

The trimeric compounds have been cleaved with a variety of neutral ligands [Eq. (41)] (154). With PPh3 the reaction proceeds smoothly, the rate and extent of reaction being dependent on the nature of R (the process occurs more readily when R is aromatic), but with isonitriles species of indeterminate constitution are obtained in addition to lAu C(OR )=NR (CNR")]. The cyclic complexes also underwent stepwise oxidative addition of bromine or iodine to yield (155) mixed gold(I)-gold(III) species, and finally the analogous gold(III) trimers. 

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. 

In conclusion, it should be noted that the Barton-Zard condensation formally might be considered as a tandem SnH-Sn ipso process (see Section III.B.3). However, the corresponding crH-complcx is stabilized here not via elimination of any auxiliary leaving group or oxidation but by means of an intramolecular nucleophilic attack on an isonitrile fragment. This is due to the amphoteric nature of isocyanoacetate ion acting at first as a nucleophile and then as an electrophile. 

However, the result is dependent on the nature of the electrophile. Thus, TMSC1 and ethyl chloroformate leads to products of alkylation after migration of the double bond.227 These products, imines of bis(trimethylsilyl)carbonyl, have been previously obtained by the insertion of isonitriles into the Si-Si bond of disilanes.201... 

Since 1948-50, by using as reactants isonitriles, phosphorus trihalides, and tertiary phosphines, we have gained important insight into the dependence of reactions of metal carbonyls with bases upon the nature of the ligand. Organophosphines were introduced into carbonyl chemistry even prior to 1948 by Reppe and Schweckendiek (7). In general, these ligands react only by substitution of CO, and do not cause disproportionation. Thus nickel carbonyl frequently reacts with complete displacement of carbon monoxide, as we were first able to demonstrate in the reaction with phenyl isonitrile (8). 

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