Pyrrolidine derivatives absolute configuration

The kainoids are a well-known group of naturally occurring, nonpro-teinogenic amino acids of general structure 1 (Figure 1). They vary only in the nature of the C-4 substituent (which is always attached to the pyrrolidine ring via an sp2 center) and the absolute configuration at this position. All of the isolated derivatives exhibit S absolute stereochemistry at C-2 and a trans relative disposition of the C-2 and C-3 substituents. 

Scheme 1.15. Diastereoisomeric fulleroproline derivatives used (among other compounds) to establish the empirical relationship between the absolute configuration of the stereogenic center of the pyrrolidine ring and the sign of the ca. 428 nm CD band displayed by fulleroprolines.

Naturally occurring levorotatory nicotine (4) has the S- absolute configuration. Its enantiomer, R-(+)-nicotine, was decidedly less potent than the naturally occurring material in assays for peripheral effects (99). The pyrrolidine methyl quaternary derivative of S-(-)-nicotine (50) shows peripheral activity com-... 

Interestingly, 716, in which a p-methoxybenzyl ether replaces the benzyl ether as a protecting group, undergoes the [3 + 2] cycloaddition with dimethyl acetylene dicarboxylate to provide exclusively and in 48% yield the cycloadduct 717, whose absolute configuration was established by an NOE difference spectral analysis of a synthesized pyrrolidine derivative. The reaction of 716 with methyl crotonate provides a 10 1 separable mixture of cycloadducts 718 which are converted to the pyrrolidine 719 [215] (Scheme 157). 

A chiral example of phosphazene bases was synthesized by treatment of (5)-2-(dialky-laminomethyl)pyrrolidine derived from 5-oxo-(5)-proline, with phosphorus pentachloride and subsequent addition of gaseous ammonia. The phosphazenes were isolated as HBF4 salts in high yields and fully characterized by H, and P NMR spectroscopy, various ID and 2D NMR experiments and mass spectrometry (El). The molecular structure and the absolute configuration of the HBF4 salts were determined by X-ray analysis [16]. 

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