4746-96-7Relevant academic research and scientific papers
A novel strategy for the asymmetric synthesis of (S)-ketamine using (S)-tert-butanesulfinamide and 1,2-cyclohexanedione
Taghizadeh, Mohammad Javad,Gohari, Seyed Jamal Addin,Javidan, Abdollah,Moghimi, Abolghasem,Iman, Maryam
, p. 2175 - 2181 (2018/08/29)
Abstract: We present a novel asymmetric synthesis route for synthesis of (S)-ketamine?using a chiral reagent according to the strategy (Scheme 1), with good enantioselectivity (85% ee) and yield. In this procedure, the (S)-tert-butanesulfinamide (TBSA) acts as a chiral auxiliary reagent to generate (S)-ketamine. A series of new intermediates were synthesized and identified for the first time in this work (2–4). The monoketal intermediate (1) easily obtained after partial conversion of one ketone functional group of 1,2-cyclohexanedione into a ketal using ethylene glycol. The sulfinylimine (2) was obtained by condensation of (S)-tert-butanesulfinamide (TBSA) with (1), 4-dioxaspiro[4.5]decan-6-one in 90% yield. The (S)-N-tert-butanesulfinyl ketamine (3) was prepared on further reaction of sulfinylimine (2) with appropriate Grignard reagent (ArMgBr) in which generated chiral center in 85% yield and with 85% diastereoselectivity. Methylation of amine afforded the product (4). Finally, the sulfinyl- and ketal-protecting groups were removed from the compound (4) by brief treatment with stoichiometric quantities of HCl in a protic solvent gave the (S)-ketamine in near quantitative yield. Graphical abstract: [Figure not available: see fulltext.].
Improved methods for thermal rearrangement of alicyclic α-hydroxyimines to α-aminoketones: Synthesis of ketamine analogues as antisepsis candidates
Elhawi, Hagit,Eini, Hadar,Douvdevani, Amos,Byk, Gerardo
experimental part, p. 6784 - 6807 (2012/09/07)
Ketamine is an analgesic/anesthetic drug, which, in combination with other drugs, has been used as anesthetic for over 40 years. Ketamine induces its analgesic activities by blocking the N-methyl-D-aspartate (NMDA) receptor in the central nervous system (CNS). We have reported that low doses of ketamine administrated to patients before incision significantly reduced post-operative inflammation as reflected by reduced interleukin-6 (IL-6) sera-levels. Our data demonstrated in a rat model of Gram-negative bacterial-sepsis that if we inject a low dose of ketamine following bacterial inoculation we reduce mortality from approximately 75% to 25%. Similar to what we have observed in operated patients, the levels of TNF-α and IL-6 in ketamine-treated rats were significantly lower than in septic animals not treated with ketamine. On the base of these results, we have designed and synthesized series of new analogues of ketamine applying a thermal rearrangement of alicyclic α-hydroxyimines to α-aminoketones in parallel arrays. One of the analogues (compound 6e) displayed high activity in down-regulating the levels of IL-6 and TNF-α in vivo as compared to ketamine.
Chiral acetals in organic synthesis: Regioselective synthesis of 2-and 3-hydroxy acetals from 2,3-olefinic acetals. Reinvestigation and further applications
Vankar, Yashwant D.,Reddy, M. Venkatram,Chaudhuri, Narayan C.
, p. 11057 - 11078 (2007/10/02)
Achiral as well as chiral 2,3-olefinic acetals are converted into 2- and 3- hydroxy acetals via LAH reduction of the corresponding epoxides and via bromohydrins followed by TBTH reductions respectively. Synthesis of 1,3-diones is described. Compounds from chiral systems are further utilized for asymmetric synthesis.
Ultrasound-Promoted Cycloadditions in the Synthesis of Salvia miltiorrhiza Abietanoid o-Quinones
Lee, Junning,Snyder, John K.
, p. 4995 - 5008 (2007/10/02)
The ultrasound-promoted Diels-Alder reaction of 3-methyl-4,5-benzofurandione with appropriately substituted vinylcyclohexenes has led to the synthesis of tanshinone IIA, nortanshinone, tanshindiol B, methyl tanshinonate, and tanshinone IIB, biologically active metabolites of the Chinese traditional medicine, Dan Shen, prepared from the roots of Salvia miltiorrhiza Bunge.Methyltanshinquinone, the dihydro derivative of the natural product, methylenetanshinquinone, was similarly prepared.The effect of ultrasound in promoting the cycloadditions parallels that of high pressure and improved the regioselectivity in favour of the natural isomers.
REGIOSELECTIVE REDUCTIONS OF 2,3-EPOXY ACETALS WITH ZINC-CHLOROTRIMETHYLSILANE AND LITHIUM ALUMINIUM HYDRIDE: CONVENIENT SYNTHESIS OF 1,2 AND 1,3-DIONES
Vankar, Yashwant D.,Chaudhuri, Narayan C.,Rao, C. Trinadha
, p. 551 - 554 (2007/10/02)
A variety of 2,3-epoxy acetals have been found to undergo regioselective reductions with zinc-chlorotrimethylsilane and lithium aluminium hydride to give 2-hydroxy and 3-hydroxy acetals respectively.Their oxidation followed by hydrolysis furnished the corresponding 1,2- and 1,3-diones in good yields.
Arynic Condensatiopn of Ketone Enolates. 17. New General Access to Benzocyclobutene Derivatives
Gregoire, Brigitte,Carre, Marie-Christiane,Caubere, Paul
, p. 1419 - 1427 (2007/10/02)
Arynic condensation of 1,2-diketone monoketal enolates appeared to be a very simple way to synthesize benzocyclobutene derivatives.X-ray diffraction and 1H NMR spectra allowed us to determine the structure of the new compounds and to propose a mechanism concerning these condensations.Finally, during this work we devised a new and easily performed two-step synthesis of 1,2-diketones.
4-Sustituted-3,4-dihydro-3-methyl-2H-1,3-benzoxazin-2-ones. III. Solvolytic-Reductive Transformation of 4-(2-Keto-)-benzoxazin-2-ones into Oxazin-2-ones
Bobowski, George,Shavel, John
, p. 277 - 287 (2007/10/02)
A series of 4-(2-keto-substituted)-3,4-dihydro-3-methyl-2H-1,3-benzoxazin-2-ones 1 (Table I, was synthesized by condensation of 3-alkyl-3,4-dihydro-4-hydroxy-2H-1,3-benzoxazin-2-ones 4 with ketones 5 having active alpha hydrogens.In the presence of alcoholic potassium borohydride, compounds 1 underwent reductive transacylation to give 1,3-oxazin-2-one derivatives 3 (Table III, a,b,c).When the other side of the ketone possessed substituents other than hydrogen, there were always also normal reduction products, i.e., secondary alcohols 2 (Table II) in addition to 3.
