Total synthesis of kuehneromycin

We next investigated the total synthesis of kuehneromycin A (7). Partial hydrolysis of 111 in trifluoroacetic acid (TFA) gave alcohol, which was oxidized to keto-lactone 112 (Scheme 18). Treatment of 112 with TFA followed by triethylamine caused unexpected decarboxylation, providing a mixture of kuehneromycin B (113) and panudial (114), which are known as natural products related to 7 [3]. The synthesis of... 

Research by J. Jauch showed that in the case of highiy base-sensitive substrates the Baylis-Hillmann reaction can be carried out by using lithium phenylselenide, which is a strong nucieophile but oniy weakiy basic. This variant of the reaction is highly diastereoselective and was successfully applied to the total synthesis of kuehneromycin... 

Jauch, J. A short total synthesis of kuehneromycin A. Angew, Chem, Int, Ed, Engl, 2000, 39, 2764-2765. 

As the total synthesis of mniopetal E (5) was compleated, we next focused our attention on mniopetal F (6) and kuehneromycin A (7) as synthetic targets. The retrosynthesis of 6 and 7 is shown in Scheme 13. We anticipated that the IMDA reaction of the substrate G would proceed favorably via a chair-like enrfo-transition state F, which would lead to the desired adduct E. In general, a substituent neighboring the dienophile part would dispose of the sterically less-demanding equatorial orientation in the transition state. However, the trialkyl-... 

Jauch achieved the short and elegant total synthesis of mniopetals during almost the same period in which our total syntheses were reported [36-41]. We briefly introduce Jauch s achievements on this subject. The key step of his synthesis was the IMDA reaction of 2-substituted butenolide 124 (Scheme 20), which was prepared by the diastereoselective PhSeLi-induced Baylis-Hillman reaction of 122 and Feringa s butenolide 123 [99]. The cycloadduct of this IMDA reaction 125 was transformed into kuehneromycin A and mniopetals E and F, respectively. 

In summary, we completed the total syntheses of (-)-mniopetal F (6) and (-)-kuehneromycin A (7) in their natural forms. Our total synthesis feature a the highly ewdoselective IMDA reaction using some substrates carrying a trialkylsilyloxy group at C-l. The n-facial selectivity in the IMDA reaction was controlled by the stereoelectronic effect of the silyloxy group adjacent to the dienophile part. 

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