Welwitindolinones

Figure 4.67 Synthesis map showing starting materials used for the synthesis of welwitindolinone A.

Table 4.34 Sum mary of reaction metrics and synthesis tree parameters for welwitindolinone A ranked...

Figure 4.68 Hypsicity profiles for the Baran (a) and Wood (b) synthesis plans for welwitindolinone A.

Ready, J.M., Reisman, S.E., Hirata, M. et al. (2004) A Mild and Efficient Synthesis of Oxin-doles Progress Towards the Synthesis of Welwitindolinone A IsonitrUe. Angewandte Chemie International Edition, 43, 1270-1272. 

Baran, P.S. Richter, J.M. (2005) Enantioselective Total Syntheses of Welwitindolinone A and Fischerindoles I and G. Journal of the American Chemical Society, 127, 15394-15396. 

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

Three new chlorinated welwitindolinone alkaloids, e.g. 218, have been isolated from the terrestrial cyanophytes Fischerella muscicola and Fischerella major [169]. 

Jimenez JI, Huber U, Moore RE, Patterson GML (1999) Oxidized Welwitindolinones from Terrestrial Fischerella ssp. J Nat Prod 62 569... 

Smith CD, Zilfou JT, Stratmann K, Patterson GML, Moore RE (1995) Welwitindolinone Analogues that Reverse P-Glycoprotein Mediated Multiple Drug Resistance. Mol Pharmacol 47 241... 

Brown LE, Konopelski JP (2008) Turning the Comer Recent Advances in the Synthesis of the Welwitindolinones. Org Prep Proc Int 40 411... 

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). 

Epoxidation of the cyclohexene bond of the latter to give 16, followed by intramolecular Friedel-Crafts-type chemistry would finally afford compound 4, containing the welwitindolinone skeleton [ 1 ]. The origin of the isothiocyanate unit in compounds such as 1 is less clear and this group has been proposed... 

Some crucial details of this biosynthetic proposal have recently been challenged. In particular, it has been proposed that the role of 12 as an intermediate is unlikely because of the absence of architectures similar to that of 12 among the known natural members of the hapalindole-fischerindole-welwitindolinone family. Instead, fischerindole I has been proposed as the actual precursor to welwitindolinone A 6, a hypothesis that is supported by synthetic studies (Sect. 5.2) [11]. 

Synthetic Efforts Towards Welwitindolinone C Isothiocyanate (Welwistatin)... 

---