Cbz-L-alanine

Phosphonium salt 482, which can also be prepared from alcohol 437 by treatment with methyltriphenoxyphosphonium iodide followed by triphenylphosphine, has been used in a stereoselective synthesis of 6-ep/-D-purpurosamine B (494) (Scheme 69) [122]. A Wittig reaction of the ylide generated from 482 and Cbz-L-alaninal (488) affords the Z-olefin 489. lodocyclization gives the trans-cyclocaihamatQ 490 in quantitative yield. Removal of the iodo group, hydrolysis of the acetonide, and benzoylation fhmishes 491. 

The final processing of racemic G20 to obtain (—) 2 proceeded smoothly, and subsequently, chemical resolution was effected by iV-acylation with N-CBZ-L-alanine with separation of the resulting diastereomers. 

In one of the steps in the synthesis of thienopyridine metalloprotease inhibitors possessing anticancer and antiinflammatory activities, the pyridine ring is constructed by treating (3-(2-thienyl)-D-alanine (274) with formaline in an acidic medium (1998EUP803505, 1999PCT9906410). In particular, this method was used to prepare 6-(R)-amino acid 275 in 91% yield. AT-Cbz-(3-(2-Thienyl)-L-alanine amide 276 was transformed into 4,5,6,7-tetrahydrothienopyridine-(65f)-carboxamide by dimeth-oxymethane in the presence of an acid (1996USP5480887). Compound 277 serves as an intermediate in the synthesis of anti-AIDS drugs. 

Ti(0 Bu)4 (100 mM) and carbobenzyloxy-L-alanine (Cbz-L-Ala, 25 mM) were mixed in toluene/ethanol and stirred at room temperature for more than 12 h. After addition of water and aging for several hours, the stock solution was diluted with toluene, and subjected to the surface sol-gel process. Uniform adsorption was observed up to 15 cycles with frequency shifts of 140-160 Hz per cycle. The template molecule, Cbz-L-Ala, was removed from the gel film by dipping in 1 wt % aqueous ammonia, as confirmed from the disappearance of characteristic peaks of the titanium-carboxylate complex and carbamate in reflection FT-IR spectra. 

N-Carbobenzyloxy-L-a-alanine was condensed with linear polyethylenimine in the presence of DCC to give polymer 48, Cbz-Ala-PEI. The protective group of polymer 48 was removed by HBr in acetic acid to yield the grafted polymer 49, HBr-Ala-PEI. This polymer was found to be grafted almost quantitatively as determined by elemental analysis and the NMR spectrum. The IR spectrum suggested the presence of an amide bond. 

Water-in-oil gel emulsions were tested in enzymatic aldolization of selected N-Cbz-amino aldehydes (Figure 19.3), N-Cbz-3-amino propanal (4), N-Cbz-glycinal, (5), (S)-N-Cbz-alaninal (6), and (R)-N-Cbz-alaninal (7) catalyzed by RAMA and L-rham-nulose-1-phosphate aldolase (RhuA) and L-fuculose-1-phosphate aldolase (FucA) from Escherichia coU [27,28]. The largest differences between conventional dimethyl formamide (DMF)/water co-solvent systems and gel emulsions were observed with RAMA and FucA catalysts (Figure 19.3). The emulsion media enhanced the catalytic efficiency of RAMA towards the N-Cbz amino aldehydes tested three, five. 

The reaction of ethyl L-lactate with A -benzyloxycarbonylbenzamide under Mitsunobu conditions produces 109 stereospecifically. Removal of the Cbz protecting group under acidic conditions gives (R)-( — )-A -benzoylalanine ethyl ester (110) [39], A host of differentially A,A-diprotected (R)-alanines (111) can be prepared analogously by reaction of 2 with an imidodicarbonate or tosylcarbamate [40]. The enantiomeric excess in Mitsunobu products 111 exceed 95%. 

N-Protected a-aminocarboxylic acid amides. A soln. of N-(4-methoxybenzyloxycar-bonyl)alanine in 4 1 dichloromethane/dimethylformamide treated with 1-hydroxy-benzotriazole and dicyclohexylcarbodiimide, stirred for 30 min, 25% aq. NH3 added, and stirred for 3-5 h until reaction complete (t.l.c.) - N-(4-methoxybenzyloxycar-bonyl)alanine amide. Y 83%. The method is high-yielding and racemization-free. F.e. inch Boc- and Cbz-aminoacid and dipeptide derivs. s. S.-T. Chen et al.. Synthesis 1989, 37-8 with 2-ethoxy-N-ethoxycarbonyl-l,2-dihydroquinoline and NH4HCO3 cf. S. Nozaki, I. Muramatsu, Bull. Chem. Soc. Japan 61, 2647-8 (1988). 

---