158981-06-7Relevant academic research and scientific papers
Application of stereocontrolled aldol coupling to synthesis of segments of immunosuppressants FK-506 and rapamycin
White, James D.,Deerberg, J?rg,Toske, Steven G.,Yakura, Takayuki
supporting information; experimental part, p. 6635 - 6641 (2011/02/26)
The sector comprising C24-C34 of FK-506 containing five of the stereogenic centers in this macrolide was synthesized from (-)-quinic acid. Aldol coupling of the C24-C34 unit with a methyl ketone representing C20-C23 of FK-506 proceeded with complete Felkin stereoselectivity to afford the C20-C34 portion of the immunosuppressant. A chelate transition state invoking coordination of a lithium enolate with a trityl ether is proposed to explain this stereoselectivity. The strategy adopted for construction of the C26-C34 moiety of FK-506 was extended to the C34-C42 subunit of rapamycin. A Mukaiyama asymmetric anti-aldol coupling was used to set in place the vicinal diol functionality at C27,28 in the C26-C33 segment of this macrolide.
