A-carboxy anhydride

WD Fuller, MP Cohen, M Shabankareh, RK Blair, M Goodman, FR Naider. Urethane-protected amino acid A-carboxy anhydrides and their use in peptide synthesis. J Am Chem Soc 112, 7414, 1990. 

UNCA Urethane-protected a-amino acid A-carboxy anhydride... 

Note 3 Propagation in chain polymerization usually occurs without the formation of small molecules. However, cases exist where a low molar-mass by-product is formed, as in the polymerization of oxazolidine-2,5-diones derived from amino acids (commonly termed amino acid A-carboxy anhydrides). When a low-molar-mass by-product is formed, the adjective condensative is recommended to give the term condensative chain polymerization. 

Bifunctional initiators such as bis-(2-glycylaminophenyl) disulfide (GAPDS) and 2 -azo-2,2 -dimethyldipropiono hydrazide (AMPH) have been used [152] to obtain hydrocaibon chain polymeric initiators with amino end groups able to promote the polymerization of amincmcid A-carboxy anhydrides (NCA) (Scheme 47). 

A-Carboxy-anhydride Base R4 k (mole" 1 sec ) Rates" of addition on two sides of ring ... 

Intramolecular asymmetric induction has also been used in electrochemistry as in the reduction of optically active alcohol esters or amides of a-keto [469,470] and unsaturated [471] acids and oximes [472] and in the oxidation of olefins [473]. A maximum asymmetric yield of 81% was obtained in the reduction of (5 )-4-isopropyl-2-oxazolidinone phenyl-glyoxylate [470]. Nonaka and coworkers [474,475] found that amino acid A-carboxy anhydrides were polymerized with various electrogenerated bases as catalyst to give the poly(amino acids) with high chirality in high yields. Conductive chiral poly(thiophenes) prepared by electropolymerization can be used for chiral anion recognition [476]. 

Phosgene reacts with 2-amino acids (usually suspended in an ether solvent) to give oxazolidine-2,5-diones (A/-carboxy anhydrides) [562,626,702,957,1064,2003] ... 

The synthesis of the angiotensin-converting enzyme (ACE) inhibitor enalapril (1) incorporates the natural amino acids L-alanine and L-proline [1,2]. Although the compound can be thought of as a derivative of homophenylalanine, this part of the compound is prepared by a reductive amination with the keto ester (2), while the amino acids are coupled through an A-carboxy anhydride 3 (Scheme 1) [3-7]. 

Whatever the "real" reasons for this peculiar behavior, interesting papers centering on the synthesis of piz/A-piz containing natural products had appeared in the chemical literature by this time (1995), notably from the laboratories of U. Schmidt,but also of C. Shin and K. Hale. All these chemists had encountered serious difficulties during the acylation of unsaturated piperazic acids and their precursors. In particular, Schmidt had discovered that only N-Cbz-valinyl chloride is sufficiently reactive to acylate a terminally protected hydrazine very similar to 88. Furthermore, Olson and Rebert had determined earlier that serinylation of piperazic acids and of its precursors by any of the common methods fails. All we could do is to confirm this conclusion even cyclic A-carboxy anhydrides (NCA s) are impotent vis-a-vis 87-88. 

Duran H, OguraK, Nakao K, ViannaSDB, Usui H (2009) High-vacuum vapor deposition and in situ monitoring of A-carboxy anhydride benzyl glutamate polymerization. Langmuir 25 10711-10718... 

Organotin compounds are also active as catalysts in the polymerizations of A -carboxy anhydrides. " The mechanism of the reaction was postulated by Freireich, Gertner, and Zilkha " to consist of addition of the organotin compound to the anhydride and formation of organotin carbamate. It subsequently decarboxylates and leaves an active -N-Sn- group that adds to another molecule of A -carboxyanhydride. This process is repeated in every step of the propagation " ... 

Olefin derivatives with electron-attracting substituents, such as, for example, acrylic compounds and dienes, as well as lactams, lactones, oxiranes, thiiranes, isocyanates, and A -carboxy anhydrides of a-amino acids, a-hydroxy carboxylic acids, and a-thiol carboxylic acids can be polymerized anionically ... 

Quantitative N-acylation of the terminal Hmb residue, even with the aid of the acyl transfer mechanism, requires special attention. As illustrated in Figure 4, an initial base-catalysed esterification occurs which is favoured through tautomer 4c. Optimal acylation occurs via symmetric anhydride (7) Protocol 4), urethane-A -carboxy anhydride (58), or pre-formed acid fluoride (59) in the apolar aprotic solvent dichioromethane, conditions which preserve the crucial hydrogen-bonded structure 4c. Typical acylation times are detailed in Table 1. 

Alanine-lactic acid, /-alanine-a-hydroxyisobutyric acid and a-amino-isobutyric acid-lactic block copolymers were prepared by copolymerization of the respective a-amino acid A-carboxy anhydride and a-hydroxy-acid-anhydrosulfite in benzene in the presence of triethylamine. Specific cleavage of the ester bonds by hydroxylamine in the cold confirmed the AB block structure of short chain lengths. 

It is well known that one of the most convenient methods for preparing high molecular weight polypeptides is the polymerization of a-aminoacid A -carboxy anhydrides in presence of initiators containing active hydrogen compounds such as primary amines or alcohols or strong bases (Scheme LXII). 

The 2-amino-2-deoxy-D-gluconic acid derivative 71 has been synthesized from 2-acetamido-2-deoxy-D-glucose, converted to the A carboxy-anhydride 72 by reaction with trichlarDmethyl chl< Dfortnate, and polymerized to polyamides of molecular weight about 10,000 daltons. ... 

Carboxy Anhydrides. The mechanism of the acid-catalyzed acylations using a carboxy anhydride as the acylating agent could be written as follows ... 

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