Pyrrolidine Analogue

Another interesting fact to be noted is that the bicyclic enamine (87) and its pyrrolidine analogue failed to undergo reduction with 98% formic acid, whereas the pyrrolidine enamine of 2-bicyclo[2.2.1]hepten-5-carboxalde-hyde (94), which exists largely in the transoid form (49), was readily reduced to (95). However, the saturated amine-substituted norbornane can be obtained directly from norbornanone under the more vigorous conditions of the Leuckart reaction (49a). 

Quinolones possessing a 7-(3-aminopyrrolidin-l-yl) substituent are particularly potent antibacterial agents. However, they often have very low solubility. Based on the observations that the hydroxymethylpyrrolidine (38) is significantly more potent against bacteria than its enantiomer (39) (the hydroxymethyl substituent in (39) apparently has a deleterious effect on activity while the same substituent in (38) has little effect on potency based on comparisons with the unsubstituted pyrrolidine analogue (40)) [84] and the enantiomer (41) is at least as potent as,... 

Fig. 7.16 Steps in the discovery of cromakalim initial structure (A), more potent pyrrolidine analogue (B) and active metabolite (cromakalim C).

C in 88% yield, the pyrrolidine analogue [300, R, R = ( 112)3] had to be heated for 1-2 days in polar solvents. The corresponding acyclic diazoamide (300, R = R = H) possessed a half-life of >10 days at ambient temperamre. The intramolecular aziridination reaction, however, could be readily achieved under catalysis using Rh2(OAc)4. 

The three closed ring group of substituents mentioned in the pyr-T recipe have also been described with this 5,6-methylenedioxy ring substitution. These could be named 5,6-MDO-pyr-T (the pyrrolidine analogue, mp 110-112 °C), 5,6-MDO-pip-T (the piperidine analogue, mp ISO-152 °C) and 5,6-MDO-mor-T (the morpholine analogue, mp 117-119 °C). To my knowledge, none of these has ever been put into man. 

Diazoamides of type 300 rapidly cyclize to form aziridines 302 (342) (Scheme 8.73). It is conceivable that this reaction proceeds through a 1,2,3-triazoline intermediate 301, which is the consequence of a LUMO(dipole)— HOMO(dipolarophile) controlled intramolecular [3 + 2] cycloaddition. Some remarkable steric effects were encountered for this cyclization. While the piperidine derivative [300, R R2 = (CH2)4] readily cyclized by diazo group transfer at 0 °C in 88% yield, the pyrrolidine analogue [300, R, R2 = (CH2)3] had to be heated for 1-2 days in polar solvents. The corresponding acyclic diazoamide (300, R1 = R2 = H) possessed a half-life of >10 days at ambient temperature. The intramolecular aziridination reaction, however, could be readily achieved under catalysis using Rh2(OAc)4. 

Curtins reaction conditions converted the A-seco-keto-acid (442) into A-nor-3-azacholest-3(5)-ene (443), which was reduced (HCl-NaBH4) to the pyrrolidine analogue (444). The keto-acid (442) reacts with hydrazine or substituted hydrazines to give 4-amino-4-aza-steroids (445)—(449). The phenylhydrazine derivatives (446) could be cyclized to the indole (450). " ... 

Enzyme Inhibition - 2-Acetamido-2-deoxy-D-glucopyranose, chitobiose and chitotriose were P-glycosidically linked to various exo-glycosidase inhibitors, and evaluated as chitinase inhibitors. Good inhibition was found for an JV-formyl-pyrrolidine analogue (transition state mimic) and epoxybutyl chitobioside (an irreversible inhibitor). ... 

These molecules were of interest to us due to our research program on the synthesis of libraries of pyrrolidine analogues possessing a-glucosidase inhibitir properties [96]. 

Several papers have dealt with pyrrolidine analogues. D-Xylose has been converted routinely to 4-amino-4-deoxy-L-arabinose, which on hydrogenation in weakly acid solution yielded 1,4-dideoxy-l,4-imino-L-arabinitol.Full details of a synthesis of 2,5-dideoxv-... 

A number of unusual and interesting furanose analogues have been reported. Iso-ddA (127) has been prepared as indicated in Scheme 20, and shown to have anti-HIV activity.231 The anti-tumour pyrrolidine analogues (128) and... 

Tethered intramolecular [3+2] nitrile oxide and nitrone cycloadditions have been investigated starting from 163. In general, NO bond cleavage proved problematical, but the reaction was successful in some cases, compound 164 converted to the tetrahydrofurans 165 and 167 (Scheme 33). Analogous cycloaddition chemistry was used to prepare the pyrrolidine analogue 278 [section S]. 

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