Pyrrolidines units

After 19 hours, no reaction between the zinc chelate 2 and benzaldehyde can be detected at 20 °C. However, 10 mol % of the zinc chelate effectively catalyzes theenantioselective addition of diethylzinc to aromatic aldehydes. The predominant formation of the S-configurated products, effected by this conformationally unambiguous catalyst, can be explained by a six-mem-bered cyclic transition state assembly17. The fact that the zinc chelate formed from ligand M is an equally effective catalyst clearly demonstrates that activation of the aldehyde moiety does not occur as a consequence of hydrogen bond formation between the ammonium proton of the pyrrolidine unit and the aldehydic oxygen. 

Chemical degradations have allowed the identification of both extremities of peripentadenine, hexanoic acid (present as an amide) and 2-hydroxy-6-meth-ylacetophenone. 13C NMR showed that the rest of the molecule included two nitrogen atoms, six methylenes, and one methine arranged in a (3-propylami-no)-l-pyrrolidine unit substituted at C-2. This formula was definitively proved by chemical degradations as well as by two total syntheses. As noted before in the cases of hygrine and of the ruspolinone alkaloids, peripentadenine is optically inactive. 

The presence of a pyrrolidine unit in complex systems such as the azabicy-clo[2.1.1]hexane unit of 2,4-methanoproline (56) lends itself to synthesis pertaining to the 1,3-disubstituted cyclobutane part of the molecule. Thus two syntheses of 56 have been published, relying on the [2 + 2] photochemical synthesis of cyclobutanes. A nontrivial problem of the synthesis of these compounds is liberation of the target molecule from its protective groups (Scheme... 

We have synthesised a number of natural products containing piperidine or pyrrolidine units using the RRM strategy (Figure 4). 

The last catalyst of Table 1.3, 30 is easily identified as a hybrid species containing motifs of both 22/23 and 27. It contains, indeed, the methyltriazolyl ring connected to the chiral pyrrolidine unit, as well as the imidazolium tag, in analogy to 27. The reaction shown in Scheme 1.12 was efficiently catalysed by 15mol.% of 30 and 5mol.% of TFA under neat conditions. Again, catalyst... 

C6— C2 unit in each case, to provide ring a + C(10) + C(6) and ring b + C(9) + C(7), respectively. The scheme employs a A -pyrrolidine unit derived from ornithine specifically labelled ornithine gave rise to radioactive tylophorine but the pattern of incorporation has not yet been established. 

The most important properties in respect to protein structures (Richardson and Richardson, 1989) are, however, not so much related to chemical reactivity. Even more important is the variation in water solubility (Hutchens, 1976) and hydrophobicity (Sueki et al., 1984) of proteins. Table 9.2.3 gives the usual assignments of acidic, basic, and hydrophobic amino acids. Solubility in water turns out to be unpredictable from first principles. Amino acids with charged side groups R are, for example, not always more soluble than those with electroneutral hydrocarbon substituents. On the contrary, by far the most soluble amino acid (1.5 kg/L ) is proline, with three CH2 groups in a pyrrolidine unit as the only substituent. Aspartic acid with an acetic acid side chain is less soluble by a factor of 250 (6g/L). Cationic amino acids are, in general, much more soluble than their anionic counterparts the effect of hydrophobic substituents (e.g., isobutyl, sec-butyl, phenyl, or indole) is not very pronounced (Table 9.2.3). 

Asymmetric induction can sometimes be improved by using an auxiliary that is attached to either the dienophile or the diene. In Rawal s synthesis of (-)-a-elemene a chiral pyrrolidine unit attached to the diene... 

The approximately 80 known pyrrolidine alkaloids possess a 5-membered nitrogen-containing ring (Massiot and Delaude, 1986 Binder, 1993). Several subgroups of pyrrolidine alkaloids arise by condensation of these units with other molecules, Pyrrolidine bases usually are modified by additional Schiff-base formation, Mannich condensation, and aldol-type processes to yield other alkaloids of tiiis general class. For example, condensation of pyrrolidine derivatives with nicotinic acid is involved in the formation of pyridine alkaloids such as nicotine see Chapter 28). Pyrrolidine units react with acetyl- or malonyl-CoA and condense via a Mannich condensation to form compounds such as hygrine and cuscohygrine and tropane alkaloids see below). 

Diacetone D-glucose has been used to construct the pyrrolidine unit 91 (Scheme 18) which was then converted to (-)-detoxin Di, the most active component of the detoxin complex. ... 

Figure 22.6 Organocatalysts bearing a pyrrolidine unit tagged to pyridinium, isoquinolinium, l,2,3 triazolium, benzimidazolium, ortetraalkylammonium cations.

The O-TMS-diphenylprolinol 103/BzOH catalytic system is also applicable as an organocatalyst of Michael reactions of nitroalkanes with a, i-enals in aqueous medium [117]. However, functionalized task-specific ionic liquids incorporated in the chiral-pyrrolidine unit, apart from being very efficient and versatile organo-catalysts of Michael and some other asymmetric reactions, show much worse behavior in asymmetric aldol reactions, where their performance is inferior to IL-supported catalysts bearing the a-amino acid fragment [118]. 

In spite of the diverse nature of alkaloid structures, two structural units, i.e. fused pyrrolidine and piperidine rings in different oxidation states, appear as rather common denominators. We therefore chose to give several examples for four types of synthetic reactions which have frequently been used in alkaloid total synthesis and which provide generally useful routes to polycyclic compounds with five- or six-membered rings containing one nitrogen atom. These are ... 

Mass spectra of pyrrolidine derivatives of methyl or ethyl esters The molecular ions are intense with characteristic fragment ions at m/zs 70, 98, and 113. The position of the double bond can be determined by locating two peaks that differ by 12 mass units. A relatively intense peak should be observed 26 m/z units higher than the lower mass peak. The double bond lies between the two peaks that are separated by 26 Daltons. 

The electric dipole moments in units 1 X 10 18 e. s. u. of these molecules and their derivatives by hydrogenation measured19 in benzene solution are the following furan, 0.670 2,5-di-hydrofuran, 1.53 tetrahydrofuran, 1.68 pyrrole, 1.80 pyrroline, 1.42 pyrrolidine, 1.57 thiophene, 0.54 and tetrahydrothiophene, 1.87. We now give a very rough interpretation of these quantities based on the bond moments given... 

Secondary amines can be added to certain nonactivated alkenes if palladium(II) complexes are used as catalysts The complexation lowers the electron density of the double bond, facilitating nucleophilic attack. Markovnikov orientation is observed and the addition is anti An intramolecular addition to an alkyne unit in the presence of a palladium compound, generated a tetrahydropyridine, and a related addition to an allene is known.Amines add to allenes in the presence of a catalytic amount of CuBr " or palladium compounds.Molybdenum complexes have also been used in the addition of aniline to alkenes. Reduction of nitro compounds in the presence of rhodium catalysts, in the presence of alkenes, CO and H2, leads to an amine unit adding to the alkene moiety. An intramolecular addition of an amine unit to an alkene to form a pyrrolidine was reported using a lanthanide reagent. 

The iV-acylamidinc unit of 71 undergoes addition of pyrrolidine in high yield to give 72 (Equation 11) <1996CHE861>. 

All four bases consist of two units a pyrrolidine and a flavonoid (or flavan), and their spectra present characteristics of both parts. Thus the UV and IR spectra resemble the spectra of the parent flavonoid (chrysine for 61 and 62, hispidulin for 64, and 4, 5-dihydroxy-7-methoxyflavan for 63). The mass spectra of 61, 62, and 63 do not easily give a molecular ion but rather show fragments pertaining to the flavonoid and to the pyrrolidine parts [m/e 84 and 83 (61 and... 

Structures of AA-methylpyrrolidines (11) are suggested by the mass spectra which exhibit the a-cleavage and parent ions increased by 14 mass units relative to those of corresponding A -H pyrrolidines. These structures are confirmed by reductive N-methylation of A -H pyrrolidines with formaldehyde in formic acid (16,25). 

The question at once arose whether this a-pyrrolidine carboxylic acid, or a-proline as Fischer termed it in 1904, was a primary product or a secondary product formed by the action of mineral acids upon other products, but its formation by hydrolysis by alkali and by the action of pepsin followed by trypsin decided that it was a primary product and therefore one of the units of the protein molecule. Sorensen, in 1905, suggested that it might arise from an a-amino-S-oxyvalerianic acid which he synthesised, but the fact that this amino acid has not yet been obtained by hydrolysis of protein and the above facts seem to exclude this possibility. 

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