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Synfacts 2023; 19(01): 0001
DOI: 10.1055/s-0042-1753156
Synthesis of Natural Products

Total Synthesis of (±)-Daphgraciline

Contributor(s):
Erick M. Carreira
,
Sven M. Papidocha
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
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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.


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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.


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Publication History

Article published online:
16 December 2022

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