BOC-L-alanine

Merucathinone was synthesized by Wolf and Pfander (79) from rerr-butoxycar-bonyl-L-alanine (Scheme 4). Treatment with n-butyllithium and styryllithium as before formed 20, which was deblocked with trifluoroacetic acid to give merucathinone (6), isolated as the oxalate. As assessed by treatment with (+)-l-phenylethyl isocyanate and HPLC, the optical purity of 6 was greater than 97%. Treatment of r-BOC-L-alanine with 3 equiv of phenyllithium gave ketone 21, which was deblocked as before to provide a short synthesis of cathinone (2), isolated as its hydrochloride (enantiomeric excess >95%) (19). 

Peptide formation with an A-protected, optically pure aminocarboxylic acid is an alternative means of obtaining diastereoisomeric derivatives of chiral aminoalkylphos-phonic acids, the diastereoisomeric products being distinguishable on a quantitative basis by P NMR spectroscopy for example, A-boc-L-alanine was used to distinguish the enantiomers of diethyl (a-aminobenzyl)phosphonate. The reaction between an enan-tiomerically enriched sample of 125 (R = H) and L-leucine methyl ester hydrochloride in the presence of DCC was followed by HPLC separation of the l,l- and D,L-peptides 126 (R = H ratio 95.3 4.7), and essentially the same procedure was applied to an analysis of 125 (R = OCH2Ph), as prepared using the bislactim ether procedure (see Section IV. C.2.b) when the final product consisted of a mixture of R,S and S,S diastereoisomers in the ratio 87.4 12.6 ... 

The electrophilic activation of terminal alkynes by arene-ruthenium(II) catalysts has provided selective access to enol esters. Enol esters are much more reactive than alkyl esters and have been used in a variety of reactions. In the past decade, Dixneuf and co-workers have developed selective approaches to the Markovnikov and antz-Markovnikov addition of carboxylic acids across alkynes by employing different arene-ruthenium(II) catalysts [48,53,54]. Of special interest is the synthesis of AT-Boc-protected 1-alanine isopropenyl ester 110 from N-Boc-l-alanine 108 and propyne 109 mediated by (Ty -cymene)RuCl2(PPh3) complex 107 (Scheme 30) [53]. Addition of the amino acid 108 to the propyne 109 proceeded exclusively in the Markovnikov sense and without accompanying racemization of the substrate. 

Ohba s group employed this methodology in two different synthetic strategies for preparing 372, a key intermediate in their synthesis of (-)-normalindine 374 (Scheme 1.102). Acylation of lithiomethyl isocyanide with A-Boc-L-alanine methyl ester gave 370 that was deprotected and alkylated with 2-(3-indolyl)ethyl bromide... 

The catalytic activity of imprinted materials would also be improved if the active sites were located primarily at the solid liquid interface, owing to better mass transfer of reactants and products into and out of these sites. Emulsion polymerization is, as already mentioned, a means by which imprinted polymers can be prepared with a high surface area and accessible sites. This methodology has been adapted to prepare an artificial biocatalyst [67], employing oleoyl imidazole as the functional host monomer, A -a-t-Boc-L-histidine as template and 7V-a-Boc-L-alanine / -nitrophenyl ester as the substrate for hydrolysis (Fig. 20). 

N-f-Boc-L-lysine is a more complex peptide owing to the additional amino function [5] Dmab-y0-alanine and N-f-Boc-i-lysine were reacted to give the dipeptide. 

Boc-D-alanine and (S)-a-methylbenzylamine react to give the corresponding dipep tide via an EDCI [3-ethyl-l-(3-dimethylaminopropyl)-carbodiimid] coupling [86], control experiment, Boc-t-alanine and (S)-a-methylbenzylamine also reacted. 

The process was also applicable to microwave-assisted reactions. Thus, 140a, 140b, and 140 (R1 = z-Pr, R4 = indol-3-ylmethyl) were prepared in a two-step, one-pot synthesis in yields of 55%, 39%, 20%, and with 70%, 73%, 50% ee, respectively. In the first step anthranilic acid was reacted with the appropriate A-BOC-protected amino acid (glycine, L-alanine, and L-valine, respectively) in the presence of P(OPh)3 and dry pyridine under irradiation at 150 °C for 140a or conventional heating at 55 °C for 140b and 140 (R1 = z-Pr, R4 = indol-3-ylmethyl). In the second step the resulting... 

On the other hand, pyrenyl-L-alanine 184 has also been used as a conformational probe in the characterization of an artificial 4-a-helix bundle protein.11,121 The 53-residue peptide 186 incorporating one residue of 184 in each of two different helical segments was synthesized by solid-phase synthesis using a segment condensation strategy and the oxime resin. Boc-pyrenyl-L-alanine 191 was coupled just like any other amino acid by the BOP/HOBt method in DMF. CD and fluorescence studies demonstrated that the two pyrene groups were in close proximity forming an excimer complex, which is possible only when the polypeptide chain folds into a 4-a-helix bundle structure. 

A 4 L Erlenmeyer flask equipped with a mechanical stirrer was charged with the 3-(4-thiazolyl)-L-alanine dihydrochloride (125.9 g) and tetrahydrofuran (1.5 L) and the mixture was adjusted to pH 6.6 with saturated aqueous sodium bicarbonate. The resultant solution was then adjusted to pH 8.9 with 3.0 M NaOH and a solution of di-tert-butyldicarbonate (117.8 g, 0.51 mol) in tetrahydrofuran (150 ml) was added. The reaction mixture was vigorously stirred at room temperature for 40 h. The tetrahydrofuran was removed under vacuum, the pH of the residue was adjusted to 2.0 with 3.0 M HCI and the mixture was extracted with ethyl acetate (3x300 ml). The combined extracts were dried over MgS04, filtered, and concentrated to give 150.0 g of a white solid. Recrystallization from hot 1 1 ethyl acetate/hexane (1.06 L) gave 107.6 g (82 %) of the desired N-boc-3-(4-thiazolyl)-L-alanine, melting point 115°C. 

Enantiospecific syntheses have utilized the chirality available in D-alanine and L-alanine. For instance, coupling and cyclization (after the necessary deprotection) of N-allyl-N-BOC-D-alanine with L-alanine methyl ester, followed by lithium aluminum hydride reduction of the diketopiperazine provided (—)-(2R,5S)-l-allyl-2,5-dimethylpiperazine (Scheme 6) [27,39], Ra-cemization was not observed during the synthesis. 

N-Protected a-amiito acids.1 A wide variety of nucleophiles attack this lactone at the 0-carbon to provide optically pure N-protected a-amino acids. The preparation of N-Boc-0-(pyrazol-l-yl)-L-alanine (2) is typical. This unusual a-amino acid occurs in watermelon seeds. 

McCague R, Taylor SJC. Integration of an acylase biotransforma-tion with process chemistry a one-pot synthesis of N-t-Boc-L-3-(4-thiazolyl)alanine and related amino acids. In Chirality in Industry n. Collins AN, Sheldrake GN, Crosby J, eds. 1997. John Wiley Sons, New York. pp. 184—206. 

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