Synthetic studies of the 18-membered antitumor macrolide, tedanolide. 3. Stereocontrolled synthesis of the C1-C12 part via a synthesis of the C1-C7 fragment by a mismatched but efficient sharpless dihydroxylation and its coupling with the C8-C11 fragment.
The C1-C12 part (4) of tedanolide (1) was synthesized starting from methyl (R)-3-hydroxy-2-methylpropionate (11a) via a coupling between the C1-C7 aldehyde (6) and the C8-C11 iodoalkene (7a). For a synthesis of 6, a mismatched but highly efficient Sharpless dihydroxylation of the alpha, beta-unsaturated ester (15) with AD-mix-alpha was successfully applied. Compound 7a was synthesized using hydrozirconation to the alkyne (32).
Matsushima
T
T
Faculty of Pharmaceutical Sciences, Hokkaido University, Sapporo, Japan.
Mori
M
M
Zheng
B Z
BZ
Maeda
H
H
Nakajima
N
N
Uenishi
J
J
Yonemitsu
O
O
D000900:Anti-Bacterial Agents / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000737:chemistry*; D003500:Cyclization; D006900:Hydroxylation; D007783:Lactones / Q000737:chemistry; D018942:Macrolides; D008958:Models, Molecular; D008968:Molecular Conformation; D013237:Stereoisomerism
D000900:Anti-Bacterial Agents; D000903:Antibiotics, Antineoplastic; D007783:Lactones; D018942:Macrolides; C119775:tedanolide