A- benzyl analogs

Enzymatic oxidation in vivo by the NAD NADH system of the carrier part to the ionic pyridinium salt prevents its elimination from the brain, while elimination from the general circulation is accelerated. Subsequent cleavage of the quaternary carrier-drug species results in sustained delivery of the drug in the brain and a facile elimination of the non-toxic carrier part (trigonelline or its A-benzyl analog). 

The high stereoselectivity seems to be general indeed, the reaction of its A -benzyl analog with (ethoxy)ethene gives the advanced precursor of daunosamine as a single cycloadduct62. 

Bailey and coworkers have explored the stereoselectivity of the Pictet-Spengler reaction with L-tryptophan esters [330]. They found that use of TFA could effect kinetically-controlled cyclization. For 1,3-disubstituted p-carbolines, the preference was for the cA-1,3 product (diequatorial). For 1,2,3-trisubstituted (A-benzyl) analogs, the kinetic preference is for cw-l,3-diaxial product. A particularly useful derivative was obtained by converting the ester group to cyanomethyl. Originally the cyanomethyl derivative was cyclized via the enamide prepared from methyl propiolate, and gave a 3 1 cis trans ratio [331]. 

The alkylation of 37a with aUylbromide and benzylbromide in the presence of n-BuLi gave A-allyl and A-benzyl analogs, 37g and 371, in 92 and 84% yields, respectively. Moreover, 9,10-DCA-photosensitized reaction of methyl analog (37b) and isopropyl analog (37c) in MeCN gave A-formyl analog (37m) and 37a in 100 and 46% yields, respectively. 

The benzylic position in alkylbenzenes is analogous to the allylic position in alkenes. Thus a benzylic C—H bond, like an allylic one, is weaker than a C—H bond of an alkane, as the bond dissociation energies of toluene, propene, and 2-rnethylpropane attest ... 

The thenyl chlorides appear to be more reactive in nucleophilic aliphatic substitution than the benzyl analogs. Thus, 2-thenyh chloride gives, in the reaction with sodium cyanide in ethanol, a mixture of ethyl 2-thenyl ether (25% yield) and 2-thenyl cyanide (32% yield), whereas benzyl chloride gives a high 3deld of benzyl cyanide uncontaminated with benzyl ether. When 2-thenyl chloride and benzyl chloride were allowed to compete for a deficiency of sodium amyloxide, 2-thenyl chloride reacted three times faster. In acetone solution 2-thenyl cyanide is obtained smoothl. ... 

The benzindolopyrrocoline system (413) was obtained by oxidative cyclization of the l-benzyl-l,2,3,4-tetrahydro-j8-carboline derivative (337 R = H or CHg) using either ferricyanide or silver oxide, a reaction analogous to that described by Robinson and by Schopf... 

Analogous side-chain oxidations occur in various biosynthetic pathways. The neurotransmitter norepinephrine, for instance, is biosynthesized from dopamine by a benzylic hydroxylation reaction. The process is catalyzed by the copper-containing enzyme dopamine /3-monooxygenase and occurs by a radical mechanism. A copper-oxygen species in the enzyme first abstracts the pro-R benzylic hydrogen to give a radical, and a hydroxyl is then transferred from copper to carbon. 

Sulfur ylids containing a benzylic group (analogous to 18) undergo an analogous rearrangement. 

Complexes of the type RMn(CO)5, where R is a primary alkyl group, undergo facile CO insertion at room temperature. Carbonylated to the corresponding acyls have been the pentacarbonyls with R = Me 50, 69), Et 51, 70), n-Pr 51), and CHjSiMe, 243). The phenyl compound, PhMn(CO)j, also inserts CO, but the benzyl analog does not 51). The claim 194) that CX3Mn(CO)5 (X = H, D, or F) converts to CX3COMn-(CO) ( < 5) upon irradiation in an Ar matrix at 17°K has been disputed 209). Carbon monoxide dissociation and recombination have been proposed instead for MeMn(CO)5. 

Using a procedure analogous to 8.4.1.A, the benzyl halide is replaced by a simple bromo-or chloroalkane (1.5 mmol) and the two-phase system is stirred at room temperature for 12 h. The reactive iodoalkane (4.5 mmol) is then added and the reaction mixture is stirred for a further 5 h. The unsymmetrical ketone is isolated as described in 8.4.I.A. 

The addition of thiobenzoyl isocyanate to norbornene and norbornadiene resulted in the thiazinones 230 (R = Ph) and 231, respectively (67CB685). The ter/-butyl- and mesityl-substituted analogs of 230 were prepared by the same method. In the case of a benzyl substituent, the derivative 232 containing an exo double bond was formed (81CB549). 

Phentolamine is also a derivative of imidazoline that exhibits a direct a-adrenoblocking, muscle-relaxant effect on smooth muscle as well as cholinomimetic, histamine, and sympathomimetic effects. The chemical variation of its stmcture permits a few of its properties to be more expressed. For example, the aforementioned tolazoline, 2-benzyl-2-imidazoline, a structural analog of phentolamine, has more of an expressed muscle-relaxant effect on smooth muscle than an a-adrenoblocking effect. 

Nicardipine Nicardipine, l,4-dihydro-2,6-dimethyl-4-(3-nitrophenyl)-methyl-2-[(methyl-phenylmethyl)-amino]ethyl ester 3,5-pirididincarboxylic acid (19.3.7), is synthesized in a manner analogous to the synthesis of nifedipine, the only difference being that in the Hantsch synthesis, two different )3-dicarbonyl compounds are used simultaneously with o-nitrobenzaldehyde. During this, one of these in the enamine form of acetoacetic ester is simultaneously used as an amine component. A heterocycUzation reaction is accomplished by reacting, the methyl ester of 8-aminocrotonic acid with the 2-methyl-2-benzyl-aminoethyl ester of acetoacetic acid [24-27]. 

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