Formal total synthesis of fostriecin by 1,4-asymmetric induction with an alkyne-cobalt complex.
The synthesis of a protected dephosphofostriecin, and thereby a formal synthesis of fostriecin, has been accomplished. The synthetic challenges were the construction of four stereogenic centers and the conformationally labile cis-cis-trans-triene moiety. Previous total syntheses have employed at least two asymmetric reactions that required the use of an external chiral auxiliary. Although remote stereoinduction in a 1,4-relationship is considered difficult, we have developed a notable 1,4-asymmetric induction that utilizes an alkyne-cobalt complex for the control of C5 stereochemistry by the C8 stereogenic center. The stereochemistry at C11 was established by 1,3-asymmetric induction with a higher-order alkynyl-zinc reagent. Thus, only one asymmetric reaction requiring an external chiral auxiliary was employed in this route. The labile cis-cis-trans-triene unit was constructed at a late stage of the synthesis by diastereoselective coupling of a dienyne and an aldehyde unit, followed by reduction.
Hayashi
Yujiro
Y
Department of Industrial Chemistry, Faculty of Engineering, Tokyo University of Science, Kagurazaka, Shinjuku-ku, Tokyo 162-8601, Japan. hayashi@ci.kagu.tus.ac.jp
Yamaguchi
Hirofumi
H
Toyoshima
Maya
M
Okado
Kotaro
K
Toyo
Takumi
T
Shoji
Mitsuru
M
D000480:Alkynes / Q000737:chemistry*; D002384:Catalysis; D003035:Cobalt / Q000737:chemistry*; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000737:chemistry; D011090:Polyenes / Q000138:chemical synthesis* / Q000737:chemistry; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry
D000480:Alkynes; D009942:Organometallic Compounds; D011090:Polyenes; D011753:Pyrones; D003035:Cobalt; C040313:fostriecin