285555-76-2Relevant academic research and scientific papers
Synthesis of enantiopure (2R)-configured muscarine alkaloids via selective alkoxyl radical ring-closure reactions
Hartung, Jens,Kneuer, Rainer
, p. 3019 - 3031 (2007/10/03)
A new synthesis of (-)-muscarine, (+)-allo-muscarine, (-)-epi-muscarine, and (-)-epiallo-muscarine has been devised which utilizes selective alkoxyl radical cyclizations for constructing tri-substituted tetrahydrofuran units. Photolysis of (2R,3S)-N-(3-benzoyloxy-5-hexen-2-oxy)-4-methylthiazole-2(3H) thione in the presence of BrCCl3 provided (2R,3S,5S)-3-benzoyloxy-5- bromomethyl-2-methyltetrahydrofuran as the major product and the corresponding (2R,3S,5R)-isomer as the minor. These building blocks were converted into enantiomerically pure (+)-allo-muscarine (from the major alkoxyl radical cyclization product) and (-)-muscarine (from the minor product). Temperature and substituent effects on the diastereoselectivity of the underlying alkoxyl radical cyclization have been investigated. (-)-epi-Muscarine and (-)-epiallo-muscarine have been prepared likewise, starting from (2R,3R)-N-(3-benzoyloxy-5-hexen-2-oxy)-4-methylthiazole-2(3H)thione.
Ring closure reactions of disubstituted 4-penten-1-oxyl radicals - Towards a stereoselective synthesis of allo-muscarine
Hartung, Jens,Kneuer, Rainer
, p. 1677 - 1683 (2007/10/03)
The trisubstituted functionalized tetrahydrofurans 10, 11, 16, 18, and 19 were photochemically prepared from 2,3-syn- and 2,3-anti-configured N-(3- benzoyloxy-5-hexen-2-oxy)thiazole-2(3H)-thione anti-6, pyridinethiones 7, anti-8, and BrCCl3. The formation of tetrahydrofurans was achieved by an efficient and highly regioselective alkoxyl radical cyclization (5-exo-trig). The 2,3-anti substituted intermediates 9 and 12 cyclize stereoselectively whereas a 2,3-syn-configured O-radical affords both possible diastereomeric addition products in equal amounts. The cyclized tetrahydrofuryl methyl radicals were trapped with the bromine atom donor BrCCl3 to afford the bromomethyl-substituted cyclic ethers 10, 11, 18, and 19 in excellent yields. The utility of this reaction was stressed by conversion of one of the newly prepared tetrahydrofurans in a two-step synthesis into (+)-allo-muscarine (+)-20.
