1- pyrroline, ring chain

Antibiotics PS-5 1 [1] and PS-6 2 [2], and other related structures such as thienamycin 3 [3] (Fig. 1), comprise an interesting family of streptomycete metabolites characterized by the presence of the 7-oxo-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid system 4 carrying an exocyclic aminoethyltio substituent at C3 of the pyrroline ring and alkyl side chains at the a-position adjacent to the P-lactam carbonyl. 

The first biosynthetic studies conducted with radioactive and stable-isotope-containing substrates in S. cattleya indicated that acetate is utilized by the organism to form C-6 and C-7 carbons of the p-lactam ring glutamate constitutes the pyrroline ring the two carbons of the hydroxyethyl group attached to C-6 are both derived from the methyl of methionine and the cysteaminyl side chain attached to C-2 is derived from cysteine. It was also proposed that the bicyclic system of two BLAs, thienamycin and cephamycin C, is formed by different biosynthetic pathways. 

When the chain between the azirine ring and the alkene end is extended to three carbon atoms, the normal mode of 1,3-intramolecular dipolar cycloaddition occurs. For example, irradiation of azirine (73) gives A -pyrroline (74) in quantitative yield 77JA1871). In this case the methylene chain is sufficiently long to allow the dipole and alkenic portions to approach each other in parallel planes. 

Nucleophilic attack at the methoxyl carbon of this compound liberated an open-chain acetal anion, which acted as a powerful nucleophile and attacked a further cyclopropane molecule in a Thorpe reaction [Eq. (28)]. Rearrangement then produced a A2-pyrroline (99) in an overall yield of 60%. On addition of acid, this A2-pyrroline aromatized with a simultaneous 1,2-methyl shift and formed the dihydropyrrolizines (100). A mixture of products is obtained because hydrolysis of the acetal function competes with the final ring closure reaction. 

The nature of the substituents around the ring in intermediates (72) may determine their stabilities and the course of their subsequent transformations. It may be expected, for instance, that 3-0-substituted amino sugars will afford the pyrroline compounds (83), having the hydroxyl group (next to the ring) of the tetrahydroxybutyl chain protected and, consequently, fission of the sugar chain, as indicated in Scheme C, will not be possible. The reaction will then be the elimination of the elements... 

In most open-chain tetrapyrrols 4 pyrrole or pyrroline residues are interlinked by Cj-bridges. The heterocyclic rings carry the substituents typically for porphyrins (D lO.l). In the biliproteins which occur in plants, especially algae. 

A red colored pyrroline dye (IV, Formula 4.92) could be identified in a model reaction of furfural and alanine. This dye is formed from 4 molecules of furfural and 1 molecule of alanine. Labehng experiments with showed that one open-chain molecule of furfural is inserted into the pyrrohnone structure. The prohne/furfural reaction system indicated further that ring opening proceeds via a cyanine dye with the structure illustrated in V, Formula 4.93. Other colored compounds could be obtained by the condensation of 3,5-dihydroxy-2-methyl-5,6-dihydropyran-4-one with furfural (VI, Formula 4.94) and of 3-hy-droxy-4-methy 1-3-cy clopenten-1,2-dione (met-... 

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