Interleukin total synthesis

Madindoline A (7) and B (ent-8) are potent inhibitors of interleukin 6. In a total synthesis [21] that also intended to determine the relative and absolute configurations of these novel antibiotics, the densely functionalized cyclopen-tene-l,3-dione ring of 7 and 8 was elaborated via RCM of diene-diol 2 (Scheme 1). 

Madindoline A and (-)-madindoline B are potent and selective inhibitors of interleukin 6. The relative and absolute configuration of these natural products was determined by means of their total synthesis by A.B. Smith and S. Omura." The key step was the SAE of the indole double bond, which led to the formation of the hydroxyfuroindole ring of both compounds. 

Shishido K, Goto K, Miyoshi S, Takaishi Y, Shibuya M (1994) Synthetic Studies on Diterpenoid Quinones with Interleukin-1 Inhibitory Activity - Total Synthesis of ( )- and (-l-)-Triptoquinone A. J Org Chem 59 406... 

The same authors have reported another extension of this methodology applied to the development of the first total synthesis of the naturally occurring and biologically active product, (-l-)-frondosin A [41]. This product is known to inhibit the binding of interleukin-8, a chemokine that has been implicated in a wide range of acute and chronic inflammatory disorders, including psoriasis and rheumatoid arthritis. Moreover, it has been shown to exhibit anti-HIV activity. As shown in Scheme 20.22, the key step of this... 

Total Synthesis of Madindolines Madindo-lines are the selective inhibitors of interleukin 6 (IL-6), which is responsible for various lethal diseases like cancer cachexia, Castleman s disease,rheumatoid arthritis,hypercalcemia, and multiple myeloma. In 2005, Omura and Sunazuka published a total synthesis of madindolines via reductive amination. " The first-generation synthesis afforded the target compound in 7.8% overall yield in 19 linear steps (Scheme 39.53). 

Toshiaki S, Tomoyasu H, Satoshi O. Total synthesis of mad-indolines, potent selective inhibitors of interleukine 6, novel bioactive microbial metabolites. J. Synth. Org. Chem. Jpn. 2005 63(11) 1090-1101. 

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