Elaiophylin synthesis

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. 

Wakamatsu, T, Nakamura, H, Naka, E, Ban, Y, Synthetic studies on antibiotic macrodiolide synthesis of the A-segment of elaiophylin. Tetrahedron Lett., 21, 3895-3898, 1986. 

SCHEME 12.13 Synthesis of elaiophylin by Kinoshita-Toshima-Tatsuta [17]. 

Segments of Toshima-Tatsuta-Kinoshita synthesis of elaiophylin... 

Besides these two syntheses of elaiophylin (63), Seebach [39,40], Ziegler [41], Evans [42], and Paterson [43,44] have studied the synthesis of elaiophylin (63). 

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. 

Total syntheses of the following antibiotics and/or their aglycones are dealt with methymycin, erythromycin, pikromycin, oleandomycin, ingramycin (albo-cycline), carbomycin B, leucomycin A3 (josamycin), tylosin, mycinamicins, rosaramicin, A26771B and elaiophylin (azalomycin B). Since the total synthesis of the macrolide-like immunosuppressant FK-506 has been recently reported, it is also reviewed here. Today, erythromycin A, oleandomycin, leucomycin A3 (josamycin), tylosin and mycinamicin II are clinically important antibiotics. 

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

Scheme 26. Kinoshita-Toshima-Tatsuta s elaiophylin (azalomycin B) synthesis...

Scheme 6. The challenges in accomplishing di tereoselective aldol couplings during the late stages of a total synthesis as shown by Kinoshita s route to elaiophylin (66). (1986) °...

Examples of the use of these chiral building blocks in the synthesis of drugs and natural products abound in the literature. They include the synthesis of grahamimycin the macrocyclic component of the antibiotic elaiophylin, fungicides norpyrenophorin, pyrenophorin and vermiculin, phorcantholide I and J, which are defensive secretions of the eucarypt longicorn beetle,citronellol and a pheromone of the western corn rootworm. Clearly the monomeric chiral derivatives of PHB have a role to play in enantiomer-specific synthesis. 

A full account has been given of the synthesis of the macrodiolide elaiophylin (see Vol.20, p.264).30... 

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