- Synthesis of (3′R,5′S)-3′-hydroxycotinine using 1,3-dipolar cycloaddition of a nitrone
-
To synthesize (3′R,5′S)-3′-hydroxycotinine [(+)-1], the main metabolite of nicotine (2), cycloaddition of C-(3-pyridyl)nitrones 3a, 3c, and 15 with (2R)- and (2S)-N-(acryloyl)bornane-10,2-sultam [(2R)- and (2S)-8] was examined. Among them, l-gulose-derived nitrone 15 underwent stereoselective cycloaddition with (2S)-8 to afford cycloadduct 16, which was elaborated to (+)-1. Graphical Abstract
- Tamura, Osamu,Kanoh, Ayano,Yamashita, Masayuki,Ishibashi, Hiroyuki
-
p. 9997 - 10003
(2007/10/03)
-
- METABOLIC STUDIES WITH MODEL CYTOCHROME p-450 SYSTEMS
-
The biomimetic potential of metalloporphyrin catalysts has been studied using nicotine as the substrate.Results indicate the formation of products identical to those obtained from in vivo metabolism.
- Chauncey, M. A.,Ninomiya, Shin-ichi
-
p. 5901 - 5904
(2007/10/02)
-
- Synthesis of (3'R,5'S)-trans-3'-hydroxycotinine, a major metabolite of nicotine. Metabolic formation of 3'-hydroxycotinine in humans is highly stereoselective
-
A method for the synthesis of (3'R,5'S-trans-3'-hydroxycotinine, a major metabolite of nicotine in humans, is described. The method involves deprotonation of (S)-cotinine with lithium diisopropylamide (LDA) followed by oxidation with the transition metal peroxide oxodiperoxymolybdenum (pyridine)(hexamethylphosphoric triamide)(MoOPH) to give an 80:20 mixture of trans-/cis-3'-hydroxycotinine. The pure (>98%) trans isomer is obtained by conversion to the solid hexanoate ester, recrystallization, and cleavage of the ester by heating with n-butylamine. GC-MS analysis of urine extracts from several smokers indicated that in humans metabolic 3'-hydroxycotinine is 95-98% trans.
- Jacob III,Shulgin,Benowitz
-
p. 1888 - 1891
(2007/10/02)
-