Mesylation mechanism

The reducing agent could attack either side of the ring in the first step but it reacts with the free OH group to produce a new reducing agent and hydride delivery is intramolecular from the bottom face. The mesylation (mechanism on p. 484) does not affect the stereochemistry as no bonds are formed or broken to any of the chiral centres. 

Trifluoromethyl thiirane is formed by the action of tris(diethylamino)-phosphineon l-chloromethyl-2,2,2-trifluoroethyldisulfide [S2] (equation 73) Difluoromethyl phenyl selenide is prepared by treatment of lithium phenyl-selemde with chlorodifluoroniethane via a carbene mechanism [Si] (equation 44) Bis(2,2,2-trifluoroethyl)diselenide is formed in the reaction of 2,2,2-trifluoroethyl mesylate with lithium diselenide [84] (equation 74). 

Reaction of 3-ketoester 2-97 and acrolein 2-98 in presence of stoichiometric amounts of 2-103 led to the desired product 2-100 in 45 % yield. A transition-state model 2-99 may be postulated assuming an ion-pairing mechanism as reported for similar asymmetric transformations [37]. The diastereomeric mixture of 2-100 was transformed into 2-101 by mesylation and subsequent elimination. Despite the moderate 64% ee determined for 2-101, it was possible to obtain optically pure 2-101 by recrystallization from hexane. 

In some circumstances, the FDA processes drug reviews under the accelerated scheme. This mechanism is to review and approve drugs speedily for cases where effective therapies are lacking or in situations of rare diseases. One of the fastest approval times to date is the case of imatinib mesylate (Gleevec, Novartis—Exhibit 7.3) for the treatment of chronic myeloid leukemia (CML) it was approved in less than 3 months after the filing of an NDA with the FDA. Another example is the new AIDS drug indinavir (Crixivan, Merck), which was approved in a mere 42 days. 

The mechanism by which ergoloid mesylates produce mental effects is unknown. Pharmacokinetics Ergoloid mesylates are rapidly absorbed from the Gl tract peak plasma concentrations are achieved within 0.6 to 3 hours. The liquid capsule has a 12% greater bioavailability than the oral tablet. The mean half-life of unchanged ergoloid in plasma is about 2.6 to 5.1 hours. 

More recently, a simple synthetic route for a large scale production of 12 (2,3-0-isopropylidene-L-lyxonolactone) was described [27]. The chosen starting material was D-ribose (13), which was oxidized to the corresponding lactone 14 (Scheme 5). The latter was submitted in situ to acetonation to provide the 2,3-0-isopropylidene derivative 9, which was then mesylated at OH-5. Treatment of the crude 5-0-mesylate 15 with potassium hydroxide led to 12 according to the mechanism proposed in Scheme 5. 

Synthesis of the thymidine derivative relies on the older two-step insertion of fluorine. Thus, the hydroxyl group in 3 -deoxythymidine benzoate (51-1) is first converted to the mesylate (51-2). Reaction with potassium fluoride in hydrogen fluoride replaces the mesylate by fluorine (51-3). The fact that this reaction, as that above, proceeds with retention of the configuration mles out simple displacement as the mechanism for this transform. The presence of the methyl group at position 5 negates the need for the chlorination step. Saponification then affords the antiviral agent alovudine (51-4) [52]. 

Shimizu T, Miyakawa Y, Iwata S et al. A novel mechanism for imatinib mesylate (STI571) resistance in CML cell line KT-1 role of TC-PTP in modulating signals downstream from the BCR-ABL fusion protein. Exp Hematol 2004 32 1057-1063. 

Ulmer T, Schaich M, Platzbecker U et al. P-glycoprotein-mediated drug efflux is a resistance mechanism of chronic myelogenous leukemia cells to treatment with imatinib mesylate. Leukemia 2004 18 401 08. 

Treatment of some mesylated N,N-diallylamino sugars with triethylamine tnhydrofluoride results m the fluorination and regioselective transfer of the mtro gen atom to give, after platinum-catalyzed reductive deallylation, 2,3-ammo-fluorodeoxysugars A mechanism involving aziridimum ions has been proposed [44] (equation 32)... 

Norbornyl systems were used to study the /i-effect in the synperiplanar geometry42. The solvolyses of the mesylates (X = MeSOaO) of ewrfo-3-(trimethylsilyl)-ewrfo-2-norbomeol 12 and ewrfo-2-norborneol 13 were shown to take place via carbocationic mechanisms, and the trimethylsilyl-substituted system showed a rate acceleration of 105. 

This mechanism also accounts for the very large 5-deuterium isotope effect observed for the solvolysis of (4-D)bicyclo[2.2.2]oct-l-yl mesylate. This mechanism is also supported by theoretical calculations of 4-substituted bicyclo[2.2.2]oct-l-yl cations74. 

The reactions of the [6]- and [7]-metacyclophanols (27) with MeSC Cl in the presence of Et3N in CH2CI2 proceed rapidly to give the corresponding strained tricyclic ethers (28).23 A mesylate is formed first by attack of RSO2CI on OH, and the mesylate group is then expelled by attack of the neighbouring OMe, an intramolecular version of the 2 mechanism. 

Tosylates and mesylates are commonly used sulfonates that you need to know for the MCAT. The sulfonate ions are very weak bases and excellent leaving groups. When tosylates and mesylates are leaving groups, the reaction may proceed via an SN1 or SN2 mechanism. 

An overview of the reactions over zeolites and related materials employed in the fields of refining, petrochemistry, and commodity chemicals reviewed the role of carbocations in these reactions.15 An overview appeared of the discovery of reactive intermediates, including carbocations, and associated concepts in physical organic chemistry.16 The mechanisms of action of two families of carcinogens of botanical origin were reviewed.17 The flavanoids are converted to DNA-reactive species via an o-quinone, with subsequent isomerization to a quinone methide. Alkenylbenzenes such as safrole are activated to a-sulfatoxy esters, whose SnI ionization produces benzylic cations that alkylate DNA. A number of substrates (trifluoroacetates, mesylates, and triflates) known to undergo the SnI reaction in typical solvolysis solvents were studied in ionic liquids several lines of evidence indicate that they also react here via ionization to give carbocationic intermediates.18... 

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