Application of stereocontrolled aldol coupling to synthesis of segments of immunosuppressants FK-506 and rapamycin

James D. White; Jörg Deerberg; Steven G. Toske; Takayuki Yakura

doi:10.1016/j.tet.2009.06.030

Application of stereocontrolled aldol coupling to synthesis of segments of immunosuppressants FK-506 and rapamycin

James D. White^*, Jörg Deerberg, Steven G. Toske, Takayuki Yakura

^*この論文の責任著者

分子合成化学研究室

研究成果: ジャーナルへの寄稿 › 学術論文 › 査読

3 被引用数 (Scopus)

抄録

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.

本文言語	英語
ページ（範囲）	6635-6641
ページ数	7
ジャーナル	Tetrahedron
巻	65
号	33
DOI	https://doi.org/10.1016/j.tet.2009.06.030
出版ステータス	出版済み - 2009/08/15

ASJC Scopus 主題領域

生化学
創薬
有機化学

文献へのアクセス

10.1016/j.tet.2009.06.030

引用スタイル

@article{766633482012497888185f59828715aa,

title = "Application of stereocontrolled aldol coupling to synthesis of segments of immunosuppressants FK-506 and rapamycin",

abstract = "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.",

author = "White, {James D.} and J{\"o}rg Deerberg and Toske, {Steven G.} and Takayuki Yakura",

note = "Funding Information: J.D. is grateful to the Swiss National Science Foundation for a Postdoctoral Fellowship (SIGE-41174). Financial support was provided by the National Institute of General Medical Sciences (GM50574). ",

year = "2009",

month = aug,

day = "15",

doi = "10.1016/j.tet.2009.06.030",

language = "英語",

volume = "65",

pages = "6635--6641",

journal = "Tetrahedron",

issn = "0040-4020",

publisher = "Elsevier Ltd.",

number = "33",

}

TY - JOUR

T1 - Application of stereocontrolled aldol coupling to synthesis of segments of immunosuppressants FK-506 and rapamycin

AU - White, James D.

AU - Deerberg, Jörg

AU - Toske, Steven G.

AU - Yakura, Takayuki

N1 - Funding Information: J.D. is grateful to the Swiss National Science Foundation for a Postdoctoral Fellowship (SIGE-41174). Financial support was provided by the National Institute of General Medical Sciences (GM50574).

PY - 2009/8/15

Y1 - 2009/8/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=67650227442&partnerID=8YFLogxK

U2 - 10.1016/j.tet.2009.06.030

DO - 10.1016/j.tet.2009.06.030

M3 - 学術論文

AN - SCOPUS:67650227442

SN - 0040-4020

VL - 65

SP - 6635

EP - 6641

JO - Tetrahedron

JF - Tetrahedron

IS - 33

ER -

Application of stereocontrolled aldol coupling to synthesis of segments of immunosuppressants FK-506 and rapamycin

抄録

ASJC Scopus 主題領域

文献へのアクセス

フィンガープリント

引用スタイル