Heterocyclic proline-based

Indollne-2-carboxylic acid [79815-20-6] M 163.2, m 177"(dec), [a] -114" (c 1, N HCl). It is purified as the racemate (see [78348-24-0] in Heterocyclic Compound, Chapter 4). The S-(-)-hydrochloride [82923-76-0] M 199.7, m 133"(dec), [a] -70" (c 1, EtOH) crystallises from Et20/propan-2-ol. It is a proline based organocatalyst which promotes the enantioseleetive formation of cyclopropanes by reaction between 2-(dimethyl- 4-sulfanylidene)-l-phenyl-ethanone (for stable sulfonium ylides see Ratts Yao J Org Chem 31 1185 1966) and but-2-enals in high yields and very high stereoselectivity involving Direct Electrostatic Activation (DEA) [Kunz Mac Millan Chem Soc 127 3240 2005.]... 

Figure 1.6 Representative examples of proline-based heterocyclic organocatalysts.

Sterically and electronically tuneable and bifunctional organocatalysts based on diamides derived from proline are particularly selective in reactions of heterocyclic ketones with aldehydes.109... 

More effective is the chiral borohydride analogue developed by Corey, Bakshi, and Shibita. It is based upon a stable boron heterocycle made from an amino alcohol derived from proline, and is known as the CBS reagent after its developers. 

Dipolar Cycloadditions. Highly substituted proline derivatives can be prepared by removal of the r-Boc protecting group from the oxazinone followed by condensation of the heterocycle with an aldehyde in the presence of p-Toluenesulfonic Acid in benzene. Under these conditions, Schiff base formation and ylide generation occur. Subsequent [3 + 2] cycloaddition with a dipolarophile affords the bicyclic heterocycle, which is then de-protected to yield the desired proline derivative (eqs 10 and 11). ... 

In general, sila-heterocycles are believed to be promising candidates for the development of silicon-based dmgs and agrochemicals. For example, the sila-proline ester 184 was prepared as part of a systematic study of silicon-containing amino acids and proteins <2000JOM19>. 

There are four amino acids, amongst the 20 that make up proteins, that have an aromatic side-chain, and of these, two have a heteroaromatic side-chain - histidine, with an imidazole, and tryptophan, with an indole. Both of these are amongst the essential amino acids , i.e. they need to be part of the diet since they cannot be biosynthesised by human beings. Decarboxylation of histidine produces the hormone histamine. Proline is the only heterocyclic DNA-coded a-amino acid - it is based on pyrrolidine hydroxyproline is an essential component of collagen, the hbrous structural protein that supports tissues and is the main component of cartilage. 

Aldol reaction. Aldol reaction catalyzed by proline and derivatives has been reviewed. A ball-mill operation on cycloalkanones, ArCHO with (5)-proline leads to predominantly anri-aldol products. The aldol reaction between 4-tetrahydrothiapyrone with the racemic 3-aldehyde based on the same heterocycle shows excellent enantiotopic group-selectivity and thence manifesting dynamic kinetic resolution. ... 

These compounds were first introduced in Chapter 5 (Section 5.6) and many are key units in important pharmaceuticals. Compounds 47-50 are secondary amines and they react as bases in the presence of a suitable acid. One important compound that contains reduced heterocyclic rings is mitomycin C (51), an important drug used to treat cancer. In contains both an aziridine ring and dihydropyrrole units. 2-Azetidinecarboxylic acid (52) shows growth inhibitory activity on cultures of Escherichia coli. Several important compounds contain a pyrrolidine ring, including proline (53), which is a common amino acid (see Chapter 27). Nicotine (54) is found in tobacco, and the carboxylate salt of kainic acid (55) is a neurotoxin. 

A series of tetradentate pyridyl-imine terminated Schiff-bases, bis(pyridyl-imine) terminated siloxane and other related polymers, can be used as ligands to host copper(II) ions. These CuBr2/polyL/TEMPO catalytic systems (polyL stands for polydimethylsiloxane derived pyridyl-imine terminated ligand) are effective for aerobic oxidations of primary and secondary alcohols under aqueous conditions. Chiral N,0-Hgands, e.g., inexpensive L-proline, can also be used to prepare copper catalysts that are particularly effective for the oxidation of sterically hindered, allylic or heterocyclic alcohols such as l-(3-pyridyl)ethanol, l-(2-furfuryl)ethanol. 

Mahrwald and coworkers [14] reported a new synthetic approach to carbohydrate heterocycles via three-component reactions starting from unprotected maltose, L-proline, and ethyl isocyanoacetate. The process is catalyzed by N,N-diisopropylethylamine (Huning s base) and produces glycopeptide mimetic as functionalized lactone, which was isolated in a 36% yield as syn/anti mixture 83/17. The methodology is depicted in Scheme 6.10. 

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