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. 2024 May 6;63(19):e202401107.
doi: 10.1002/anie.202401107. Epub 2024 Mar 28.

Total Synthesis of Dragocins A-C through Electrochemical Cyclization

Brendyn P Smith  1 , Nathanyal J Truax  1 , Alexandros S Pollatos  1 , Michael Meanwell  1   2 , Pranali Bedekar  1 , Alberto F Garrido-Castro  1   3 , Phil S Baran  1
Affiliations

Total Synthesis of Dragocins A-C through Electrochemical Cyclization

Brendyn P Smith et al. Angew Chem Int Ed Engl. .

Abstract

The first total synthesis of dragocins A-C, remarkable natural products containing an unusual C4' oxidized ribose architecture bridged by a polyhydroxylated pyrrolidine, is presented through a route featuring a number of uncommon maneuvers. Several generations towards the target molecules are presented, including the spectacular failure of a key C-H oxidation on a late-stage intermediate. The final route features rapid, stereocontrolled access to a densely functionalized pyrrolidine and an unprecedented diastereoselective oxidative electrochemical cyclization to forge the hallmark 9-membered ring. Preliminary studies suggest this electrochemical oxidation protocol is generally useful.

Keywords: alkaloids; electrochemistry; total synthesis.

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Figures

Figure 1.
Figure 1.
The dragocin natural products (1A-1C) and related natural product AB3217-A (2). Failed cyclization strategies towards the hallmark skeleton of the dragocin family and the final successful approach.
Figure 2.
Figure 2.
Application of the benzylic electrochemical oxidative C–H functionalization reaction towards β-hydroxy amino acid building blocks.
Scheme 1.
Scheme 1.. Total synthesis of dragocins A–C (1A-1C) and the failed late-stage C–H oxidation strategya
aFor detailed reagents and conditions, see the Supporting Information. b18 equivalents of LAH. c50 equivalents of LAH.
See this image and copyright information in PMC

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