Coniine total synthesis

Other systems different from oxazolidinones have been successfully applied as ligand of Cu(I) salts for this transformation. The use of QUINAP (L in Scheme 11.15), combined with CuBr gave excellent results in the total synthesis of (S)-(-l-)-coniine, a highly toxic alkaloid inducing curare-type paralysis, in 45% overall yield and 90%... 

SCHEME 11.47 Asymmetric total synthesis of e f-sediidine and (+)-coniine. 

SCHEME 11.51 Asymmetric total synthesis of (-)-anabasine and (-)-coniine employing an asymmetric vinylogous Mannich reaction as key step. 

SCHEME 2439. Total synthesis of coniine using ARCM. 

Coniine is a neurotoxin of which less than 200 mg is fatal to humans. It can be isolated from poison hemlock and from the yellow pitcher plant. In the body, it causes paralysis by blocking the nicotinic receptors on the post-synaptic membrane of the neuromuscular junction. It does not affect the central nervous system therefore, the poisoned remains conscious until paralysis results in cessation of respiration. The first total synthesis was published by Ladenburg in 1886, in which he evenmaUy separated racemic coniine by classic resolution with tartaric acid. Historically, it became famous being the poison used to kill Socrates. 

Total Synthesis of Coniine through Enantioselective RCM with Substrates Bearing a Tertiary Amine... 

Scheme 12.1 Total synthesis of (R)-coniine through enantio ...

The total alkaloid concentration bases of both varieties of Conium maculatum since they are a reflection of both the rate of synthesis as well as that of turnover. The large pool of y -coniceine in var. California compared with var. Minnesota would appear to be due to a combination of a faster rate of synthesis (35 m)Ltmol/hr/g) and a slower turnover (4 days) compared with the slower rate of synthesis (4.5 m/umol/hr/g) and a faster turnover (1 day) for var. Minnesota. In either case the methylation of coniine does not appear to be limiting since it did not occur at a measurable rate in var. Minnesota which had total activity and pool ratios consistent with a rapid conversion of y-coniceine into coniine. 

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