The First Total Synthesis of Elaiophylin Azalomycin B

The elaiophylin synthesis is based on an aldol reaction of the ethyl ketone 278 and the dialdehydic 16-membered-ring macrodiolide 282, which were prepared from D-glucose and 2-deoxy-t-fucose. In this synthesis, diethylisopropylsilyl (DEIPS) and isopropyldimethylsilyl (DMIPS) groups were developed and used as effective 0-protecting groups. 

The Seebach aglycone synthesis is also independently based on the aldol coupling of the dialdehydic diolide 282 and the ethyl ketone 288, which are prepared by the use of chiral building blocks, Roche ester 285 or diethyl (S)-malate (286) and ethyl (R)-3-hydroxybutyrate (287). 

The aldol reaction of 282 with 288 was accomplished by use of dibutylboron triflate to give three diastereomeric adducts. One of them was de-O-protected to give an aglycone of elaiophylin, ll,ir-di-0-methylelaiophylidene (289), which was identical with a sample prepared by methanolysis of elaiophylin (284). 

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In the first total synthesis of elaiophylin (azalomycin B 181), glycosidation of P-hydroxy ketone 178 and glycal 177 was examined (Scheme 26) [111]. NBS-promoted glycosidation [112] followed by debromination with -Bu3SnH-AIBN was first applied to give 179 in only a 30% yield. Then, the Wakamatsu procedure using CSA-MS 4A [113] was found to afford the desired 179 in 80% yield as the sole anomer, which led to 181 via aldol reaction of the (Z)-boron enolate of the ketone 179 with dialdehyde 180. 

The First Total Synthesis of Elaiophylin (Azalomycin B) [Kinoshita-Toshima-Tatsuta, 1986, 1988] (Scheme 26) [47, 48]... 

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