Li L.-X,
Min L,
Yao T.-B,
Ji S.-X,
Qiao C,
Tian P.-L,
Sun J,
*,
Li C.-C.
*
The Hong Kong University of Science and Technology, Southern University of Science
and Technology, Shenzhen, and Shenzhen Bay Laboratory, P. R. of China
Total Synthesis of Yuzurine-type Alkaloid Daphgraciline.
J. Am. Chem. Soc. 2022;
144: 18823-18828
DOI:
10.1021/jacs.2c09548
Key words
(±)-daphgraciline - daphniphyllum alkaloid - Achmatowicz reaction - (5+2) cycloaddition
- Diels–Alder cycloaddition - Benkeser reduction - reductive epoxide opening
Significance
Sun, Li, and co-workers present a synthesis of the Daphniphyllum alkaloid (±)-daphgraciline. Notably, this work constitutes the first total synthesis
of a member of the yuzurine-type subfamily. The unique bridged azabicyclo[4.3.1]decane
system combined with a spiro tetrahydropyran moiety presents a formidable challenge
to total synthesis.
Comment
Achmatowicz reaction of furfuryl alcohol B furnished dihydropyran C which was used in a subsequent (5+2) cycloaddition to elaborate the characteristic
azabicyclo[4.3.1]decane system of (±)-daphgraciline. After establishing the [6-7-5-5]
ring system of intermediate J, Benkeser reduction cleaved the ether bridge and deprotected the tosyl amide. The
free amine was methylated and the diol closed to epoxide L. A reductive epoxide opening–cyclization cascade forged the lactone in M and paved the way to (±)-daphgraciline.
