Kibayashi’s syntheses

C.iii. Nitroso-Type Compounds. Nitroso compounds (R—N=0) show reactivity as dienophiles in Diels-Alder reactions, giving heterocyclic rings. In Kibayashi s synthesis of fasicularin, " for example, hydroxamic acid 180 was treated with tetrapropylammonium periodate in the presence of 9,10-dimethyl-anthracene to give transient acylnitroso compound 181, and the resultant Diels Alder product 182 was formed in 84% yield. In this particular example, the Diels-Alder adduct essentially "protected" the acyl nitroso unit, which was used in a subsequent reaction. 

Kibayashi s group also completed the total synthesis of lepadins A, B, and C[20]. 

Alder reaction [524, 525]. Danishefsky et al. have used nitroso dienophiles for the synthesis of mitomycin K and antibiotics of the FR 900482 family, the latter ones are structurally unique aziridino-l,2-oxazine derivatives [526-529]. An approach directed to the cephalotaxus alkaloids has been worked out by Fuchs et al. [530], and several indolizidine alkaloids have been prepared by Keck s [531] and Kibayashi s groups [532,533]. Kibayashi et al. also synthesised Nuphar piperidine alkaloids in enantiomerically pure form by means of an asymmetric nitroso Diels-Alder reaction [534]. 

Recently, Kibayashi s group (85JA5534) elegantly carried out the stereo-controlled total synthesis of gephyrotoxin (skin extracts of neopropical poison dart frog) based upon an intramolecular nitroso Diels-Alder reaction. The hydroxamic acid 365 was treated with tetrapropylammonium periodate... 

Abe, H., Aral, Y., Aoyagi, S., Kibayashi, C. Synthesis of conformationally constrained spirodihydrofuropyridine analogues of epibatidine. Tetrahedron Lett. 2003, 44, 2971-2973. 

Four total syntheses of FR901483 have been reported so far the enantiocontrolled approaches of Snider [2], Sorensen [5], and Ciufolini [6], and Funk s synthesis in the racemic series [7]. Furthermore, Brummond has communicated a partial total synthesis [8] and Wardrop reported a formal synthesis of the desmethylamino analog, which had been described by Snider [9,10]. Additionally, Kibayashi and Bonjoch and co-workers have reported other synthetic entries to the azatricyclic core of FR901483, which has also been reported by Brummond in her initial studies [11-14], An overview of FR901483 synthetic studies is outlined in Table 1. 

Scheme 32. Kibayashi s alternate synthesis of the tricyclic skeleton...

Homopumiliotoxin and Pumiliotoxin were totally synthesized in the late twentieth century by Kibayashi s goup [73-75]. Intramolecular alkoxycarbonylation for the formation of lactone frames were taken as a fundamental step (Scheme 10.12). Negishi and Liao reported a palladium-catalyzed carbonylative lactonization of (Z)-cr-iodoalkenols and applied that in the total synthesis of (h-)-hamabiwalactone B [76]. 

Kibayashi s approach to the synthesis of several pumihotoxins entailed Lewis acid-catalyzed addition of the allenylsilane 2323 to (S)-2-acetylpyrrolidinium... 

Kibayashi s route to the stellettamides, like that of several other research groups, centered on the synthesis of (lS,8aR)-l-aminomethylindolizidine... 

Kibayashi C., Aoyagi S. Nitrogenous Natural Products Synthesis Via N-Acylni-troso Diels-Alder Methodology Synlett 1995 873 879... 

Aoyagi, S., Tanaka, R., Naruse, M., Kibayashi, C. (1998) Total Synthesis of (—)-Epibatidine Using an Asymmetric Diels-Alder Reaction with a Chiral N-Acylnitroso DienophUe. Journal of Organic Chemistry, 63, 8397-8406. 

During the enantioselective total synthesis of denrobatid alkaloid (-)-pumiliotoxin C by C. Kibayashi et al., an aqueous acyinitroso Diels-Alder cycloaddition was used as the key step. In the endgame of the total synthesis, the c/s-fused decahydroquinolone was subjected to the Clemmensen reduction conditions to give a 2 1 epimeric mixture of deoxygenated products in 57% yield. Subsequent debenzylation converted the major isomer into 5-ep/-pumiliotoxin C. 

Abe, H., Aoyagi, S., and Kibayashi, C., First total synthesis of the marine alkaloids ( )-fasicularine and ( )-lepadiformine based on stereocontrolled intramolecular acylnihoso-Diels-Alder reaction, J. Am. Chem. Soc., 122, 4583, 2000. 

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