Total Synthesis of Scholarisine K and Alstolactine A

Abstract

The first asymmetric total syntheses of scholarisine K and alstolactine A have been accomplished. Our syntheses feature (1) ring closure metathesis and an intramolecular Heck reaction to construct the 1,3-bridged [3,3,1] bicycle (C-D ring), (2) intramolecular alkylation followed by Fischer indolization to form the basic skeleton of akuammilines, and (3) bioinspired, acid-promoted epoxide opening/lactonization to generate the second lactone ring of alstolactine A. These results provide evidence of a biogenetic relationship between scholarisine K and alstolactine A, which should facilitate the preparation of other akuammiline-type natural products and their derivatives for functional studies.

Intramolecular Heck Reaction in Total Synthesis of Natural Products: An Update

“…in 1997 adopting intramolecular Heck reaction using Ni(COD) 2 as a catalyst [9d] . Another instance of intramolecular Heck reaction was also observed in the total synthesis of indole monoterpenoids alkaloids natural products scholarisine K ( 23 ) and alstolactine A ( 24 ) reported by Gao et al [10a] . in 2017 (Scheme 2).…”

Copper‐Catalyzed Trifluoromethylazidation of Alkynes: Efficient Access to CF3‐Substituted Azirines and Aziridines

“…Gratifyingly, the CF 3 moiety survived under these reaction conditions, and all these reactions presented excellent diastereoselecitvity because of the steric bulky of the CF 3 group. Finally, further transformation of 3 a was also conducted 13c–d. Besides triazole from the click reaction (see the Supporting Information), the pyrazoles 6 and 7 were efficiently obtained, each having a CF 3 group in a different position (Scheme ).…”

Synthesis of indole derivatives as prevalent moieties present in selected alkaloids

“…152 Scholarisine K (123) and alstolactine A (125) were extracted by Luo and co-workers in 2015 from Alstonia scholaris. 177,178 The rst enantioselective total synthesis of scholarisine K (123) and alstolactine A (125) were performed in 2017 by Gao et al 179 The key aspects of these syntheses are the ring closure metathesis and also an intramolecular Heck reaction to make the 1,3-bridged [3,3,1] bicycle (C-D ring), the intramolecular alkylation reaction was followed by the Fischer indolization reaction to make the basic framework of the akuammilines, and also the bioinspired, acid-improved epoxide opening/lactonization to form the second lactone ring of alstolactine A. The total synthesis of scholarisine K ( 123 Scheme 19 Total synthesis of (À)-quebrachamine ( 132), (À)-pyrifolidine ( 133), (À)-aspidospermine ( 134), (+)-aspidospermidine ( 135) and (+)-vincadifformine (136).…”