A Short and Efficient Enantioselective Synthesis of (+)‐(2S,3S,5S)‐epi‐Muscarine

Abstract

A short, efficient and novel enantioselective general approach for the synthesis of muscarine alkaloid and its application to the asymmetric synthesis of epi‐muscarine from readily available (R)‐PMB glycidyl ether as starting material is described. Key transformations include Sharpless asymmetric dihydroxylation (AD), regioselective epoxide ring opening and intramolecular SN2 cyclization.

Sharpless Asymmetric Dihydroxylation: An Impressive Gadget for the Synthesis of Natural Products: A Review

“…Muscarine and its derivatives are highly potent pharmacological agents that also act as acetylcholine inhibitors [ 30 ]. Owing to their wide biological importance, Gehlawat et al [ 31 ] in 2020 reported the total synthesis of epi-mucarine alkaloid by using various reactions including Sharpless asymmetric dihydroxylation, cyclization by bimolecular nucleophilic substitution reaction, and cleavage of epoxide ring. In the first step, (p-methoxybenzyl) glycidyl ether 15 was treated with propyl lithium in the presence of boron triflouride diethyl etherate followed by reduction with lithium aluminum hydride, resulting in the synthesis of compound 16 in 86% yield.…”

Exploring the synthetic potential of epoxide ring opening reactions toward the synthesis of alkaloids and terpenoids: a review

“… 17 Vinyl epoxides are important synthetic precursors in organic synthesis 18 as they lead towards the synthesis of (−)-(4 R ,5 R )-Muricatacin (a natural acetogenin) via regio or stereoselective ring opening reaction of epoxide. 19 Syntheses of numerous biological active compounds such as Sphingofungin, 20 Zoanthenol, 21 marine ladder polyethers, 22 Zampanolide, 23 epi -Muscarine, 24 Molestin E, 25 (−)-Epicoccin G and (−)-Rostratin A, 26 homoisoflavonoids, 27 Chlorotonils, 28 Lingzhiol, 29 Phomarol, 30 Isoandrographolide, 31 Citrinadins, 32 Isosilybin, 33 polyester, 34 Mupirocin 35 and Bisfuranoxide 36 etc. have been accomplished by involving epoxide chemistry.…”

Enantioselective synthesis of C1-C4 and C5-C14 fragments of cytospolide D

“…Various methods for the synthesis of cytospolide D 4 based on the chiral pool approaches have been documented in the literature. [4][5][6][7][8] As part of our ongoing program towards the syntheses of bioactive natural products, [9][10][11][12][13][14] we became interested in developing a simple and flexible route to the key fragments of cytospolide D 4. Herein, we are reporting a new and efficient enantioselective synthesis of key fragments C1-C4 and C5-C14 for the cytospolide D 4 employing the MacMillan's crossed aldol, Sharpless AD and Mitsunobu inversion reaction as key steps.…”