Strecker method

A particularly useful application of MW-assisted synthesis at elevated pressure has been in the preparation of radiopharmaceuticals containing isotopes with short half-lives, such as C-ll (half-life 20 min) and F-18 (half-life 110 min) [25-27]. Clearly, these compounds have to be synthesized very rapidly in order to give products with high radiochemical yield. For example, [1-11C] tyrosine 12 was synthesized using the two step Bucher-Strecker method by the reaction of p-hydroxyphenylacetaldehyde bisulfite adduct 11 with K11CN and (NH4)2C03 followed by hydrolysis with aqueous NaOH (Scheme 4.7)... 

Serine has been prepared by the Strecker method from glycol-aldehyde 1 and from ethoxyacetaldehyde,2 3 by the condensation of ethyl formate with ethyl hippurate followed by reduction and hydrolysis,4 5 from the reaction product of chloromethyl ether with ethyl sodium phthalimidomalonate,6 and by amination of a-bromo-/3-methoxypropionic acid with subsequent demethyla-tion.7... 

The second method, referred to as the decarbonylation reaction, concerns a base-catalyzed elimination of HC1 and CO from an acid chloride.31 The amide moiety was converted into the amino acid 15 by reaction with Na202 in water.32 Alternatively, amides can be converted into the corresponding carboxylic acid by treatment with concentrated HC1.33 However, this method produced lower yields as a result of some decomposition. The carboxylic acid 15 was treated with the Vilsmeier reagent and triethylamine furnishing the imine 16 via decarbonylation. The imine 16 was then converted, in a similar manner to the retro-Strecker method, to the unprotected homoall-ylamine 17 in 75% overall yield and an ee of 98%. 

Catalytic hydrogenation of (R,S)-22 was unsatisfactory for removal of the chiral auxiliary. The regioselectivity of the TV-benzylation step (5% Pd-C, 5 bar H2, 40°C, EtOH, AcOH) gave a (S)-l-a m i ik > - in da n e/( W) - PG A ratio of 4 6. This means that 60% of the key intermediate was converted to the undesired product. Therefore, the retro-Strecker method, analogous to the homoallylamines case, was applied as an alternative. The initially 3-step method could be improved to an efficient one-pot procedure (Scheme 25.9). 

Show syntheses of amino acids by the Strecker method, the a-substitution by NH3 method, or the Gabriel/malonate method. (Problem 26.29)... 

By employing thiolactone 8 as an intermediate for (+)-biotin (1), as well as availability of functionalities and a stereogenic center of L-cysteine as a starting material, synthetic schemes have successfully been devised. Our second approach investigates. The use of Strecker method I to obtain 8 from L-cysteine (Fig. (20)) [73]. 

The synthesis of 1 using thiolactone 8 as a key intermediate has been accomplished by Goldberg and Stembach 50 years ago [51-53], which, we believe, has thoroughly been revised by the Strecker method II. We hope the method would contribute in providing 1 of currently strong and growing demand. 

The aromatic amino acid L-methyl DOPA (Di Hydroxy PhenylAlanine) 80 is used to make an antihypertensive compound. Synthesis by the Strecker method clearly requires the aromatic ketone 77, and the synthesis follows the pattern below.18 The intermediates and final product have been resolved in various ways. 

In a modification of the Read reaction, instead of the free amino acids, their esters or amides, and especially their nitriles, are used.9 This procedure has also been termed the Strecker method on the basis of the synthesis of the starting amino nitriles. 

The hydrolysis of nitriles (58) formed in this way is usually difficult (Scheme 19). In the presence of cone, sulfuric acid mainly amides of a-keto acid oximes (59) were obtained (1), Concentrated hydrochloric acid yields amides of N-hydroxyamino acids (60) (130) while in dilute acid the desired products (1) are formed (1, 79). Taking into account the instability of N-hydroxyamino nitrile (58) and the possibility of its polymerization, the first stage of hydrolysis is carried out at lower temperature (79). The Strecker method has also been applied to the synthesis of several cyclic N-hydroxyamino acids (70, 71) (134). 

First, there are many variants of the Strecker method, two of which have been noted above, viz., in the syntheses of alanine (Ala, A) and methionine (Met, M). However, the Strecker variants all involve the addition of cyanide (CN") to an imine (or equivalent) the latter formed in situ from a carbonyl compound and a suitable equivalent of ammonia (e.g., ammonia [NH3], ammonium chloride [NH4CI], and ammonium acetate [NH4O2CCH3]). The generalized pathway is shown in Scheme 12.57. 

By tiie Strecker method of Cocker and Lapworth (162) about 200 g. 

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