Aminoalcohol esters

Aminoalcohol esters, having the following general formula, have emerged from the outstanding pharmacological actions displayed by atropine  

A follow-up from this generalised structure resulted into the formation of an altogether new breed of tropeines that possessed remarkable antimuscarinic activity. A few typical examples of this category of compounds are discussed below, namely  

The synthesis essentially consists of the following three parts  

The interaction of succinyldialdehyde, methylamine and calcium acetone dicarboxylate yields the corresponding calcium salt which on treatment with HCl and subsequent reduction gives rise to tropine. 

A molecule each of tropic acid and tropine in the persence of HCl loses a molecule of water to yield the official product. 

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The BF2 chelates are hydrolytically stable (the majority of them may be recrystallized from water) whereas the BC12 chelates are easily hydrolyzed. The boric acid ester complex triptych boroxazolidines are also stable towards hydrolysis as are other aminoalcohol esters.83 A great number of the boron chelates are colored several spectrophotometric methods are based on chelate formation81 84 for the analytical determination of boric acid, organoboric acids and chelating organic compounds. The boron chelates are remarkable for their pharmacological properties as well.84 Various aspects of the boron chelates have been reviewed.81,83-86... 

Discussion concerning aminoalcohol esters of nitric acid which are also salts of nitric acid, is developed further in the chapter devoted to nitric salts (see p. 472). 

Aminoalcohols are an important class of compounds in medicinal chemistry because many drugs contain this structure. For their resolution, there are two possibilities acylation of amino function or an enzymatic transesterification with vinyl esters through the hydroxyl group. However, the amino or hydroxyl group must be protected, because if the starting material is the free aminoalcohol, the O- and N-acylation can take place, and in addition, there are migrations obtaining... 

Zinc borohydride, which is also a useful reagent,66 is prepared by reaction of ZnCl2 with NaBH4 in THF. Owing to the stronger Lewis acid character of Zn2+, Zn(BH4)2 is more reactive than NaBH4 toward esters and amides and reduces them to alcohols and amines, respectively.67 Zn(BH4)2 reduces carboxylic acids to primary alcohols.68 The reagent also smoothly reduces a-aminoacids to (3-aminoalcohols.69... 

In a similar sequence, reaction of ketoester 52 with 2-thienylmagnesium bromide gives a modest yield of the benzilic ester 53. Transesterification of this with aminoalcohol 51, prepared analogously to 45 by starting with methylamine, gives, after quaternization with methyl bromide, heteronium bromide... 

Benzilate esters of piperidinols, as well as those of acyclic aminoalcohols, show similar anticholinergic activity. For example, ester interchange between methyl benzilate and N-methyl-4-piperidinol, followed by quaternization of the resulting ester... 

Early synthetic spasmolytics resembled atropine closely, e.g. homatropine (the ester of mandelic acid and tropine (IV)). It may be noted that acetylcholine itself is an ester of a quaternary aminoalcohol and a short-chain organic acid. If the length of the chain is increased, acetylcholine activity decreases and com-... 

Fig. 9 Three haptens, [15]—[17], containing a 1,2-aminoalcohol functionality were investigated as alternatives for esterase and amidase induction. Of antibodies raised against hapten [15], 50% were shown to catalyse the hydrolysis of ester [18], thereby establishing the necessity for a compact haptenic structure. Hapten [19] along with [16] was employed in a heterologous immunization programme to elicit both a general and acid/base function in the antibody binding site.

Y. Yamamoto and co-workers used L-aspartic acid 4-methyl ester (108) as their starting material for the synthesis of preussin [64]. The ester was transformed in nine steps to the TBDPS-protected aminoalcohol 109 (Scheme 28). Allylation of the iST-Boc-protected amine using allyl bromide... 

Similarly, lipase-catalyzed kinetic resolution has also been applied to intermediate nitrile alcohol 46 (Scheme 14.14). Best results were obtained by using immobilized Pseudomonas cepacia (PS-D) in diisopropyl ether, leading to excellent yield and enantiomeric excess of the desired (5)-alcohol 46a, along with (/J)-nitrile ester 47. Reduction of 46a with borane-dimethylsulhde complex, followed by conversion to the corresponding carbamate and subsequent lithium aluminum hydride reduction gave rise to the desired (S)-aminoalcohol intermediate 36, a known precursor of duloxetine (3). 

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