Welwitindolinone A isonitrile

Welwitindolinone A isonitrile (117) from the blue-green alga Hapalosiphon welwiischii is active against Aspergillus oryzae, Penicillium notation, Saccharomyces cerevisiae, and Trichophyton mentagrophytes [93]. 

On the other hand, oxidation of the indole system in 12 would give 15, a direct precursor of the spiro compound 6 (welwitindolinone A isonitrile). 

Welwitindolinone A isonitrile also has a number of structural features that make it a very challenging target, most notably the sterically crowded spiro-fused cyclobutane ring, which at first sight might seem thermodynamically unstable (Fig. 3). 

Two total syntheses of welwitindolinone A isonitrile have been completed so far. The first of them, due to Baran, uses a ring-contraction strategy to generate the cyclobutane ring, and is remarkable for the absence of protect-... 

Scheme 27 Retrosynthetic analysis of welwitindolinone A isonitrile by Baran...

The retrosynthetic approach to welwitindolinone A isonitrile (6) used by the Wood group is shown in Scheme 33. After recognition of the possibility of deriving the vinyl isonitrile fragment from a ketone, the disconnection of 6 to 140 was proposed. A literature report of a samarium (II) iodide-mediated reductive coupling of acrylates with isocyanates to give amides, which could be expected to lead to a new spirooxindole synthesis, prompted the disconnection of 140 to 141. This compound was to be obtained from the readily available cyclohexadiene derivative 143, by way of bicyclic ketone 142. 

Scheme 38 Failed route to welwitindolinone A isonitrile by Wood...

Terminal alkenes, both mono- and disubstituted, have been prepared using the title reagent. In Wood s recently disclosed synthesis of welwitindolinone A isonitrile, he achieved a selective dehydration of the less hindered secondary alcohol in 32 to yield monosubstituted alkene 33. 13 Mori obtained terminal disubstituted alkene 35 in 93% yield from phosphorylated tertiary alcohol 34 in the penultimate step in his total synthesis of acoradiene (36), the aggregation pheromone of the broad-homed flour beetle.14... 

The spiraled architecture of welwitindolinone A isonitrile 196 has inspired the development of a variety of strategies for its construction. A beautifully simple protecting group-free synthesis of (-F)-welwitindolinone A has been achieved by Baran and coworkers [115-117]. As depicted in Scheme 48, the key step for installation of the aU-carbon quaternary center at oxindole C3 involved fluoro-hydroxylation of (—)-fischerindole 1 194 via treatment with aqueous Xep2. The desired natural product, 196, was obtained as a single diastereomer in 44% yield. The origin of the asymmetry at oxindole C3 can be traced back to enantiopure carvone oxide. 

The Wood group has detailed extensive studies directed toward the total synthesis of ( )-welwitindolinone A isonitrile (Scheme 49) [118]. In one approach that did not materialize into a viable route to ( )-l%, an intricate spirocyclization... 

Welwitindolinone A isonitrile (271) [108], one of several related oxindole-con-taining alkaloids, such as hapalindole (272) [109, 110], fischerindole (273) [108], and ambiguine H (274) [111, 112], was isolated from blue-green algae by Moore... 

Wood and coworkers reported their independent synthesis of welwitindolinone A isonitrile (271) [112], which featured a Sml2-mediated generation of... 

Total synthesis of welwitindolinone A isonitrile by Wood and coworkers... 

Reisman SE, Ready JM, Hasuoka A, Smith CJ, Wood JL (2006) Total synthesis of ( )-welwitindolinone A isonitrile. J Am Chem Soc 128 1448-1449... 

Scheme 1.16 Use nf a chloronium inn-mediated semipinacol rearrangement in the total synthesis nf l+l-welwitindolinone A isonitrile (104h a...

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