Isoquinuclidine, preparation

On the other hand, novel diastereomeric p-amino thiol ligands possessing an isoquinuclidine skeleton have been readily prepared by Hongo et al. via imino-Diels-Alder reactions.As shown in Scheme 3.15, when applied to the enantioselective addition of ZnEt2 to various aldehydes, one of these ligands afforded the products with high enantioselectivities of up to 94% ee. 

The Diels-Alder reaction of chiral 1,2-dihydropyridine 98, which can be prepared as a single enantiomer from L-lysine, with iV-acryloyloxazolidinone 99 gave 2-azabicyclo[2.2.2]octene product 100, which was converted into isoquinuclidine 101 with 97% ee (Scheme 26) <2000TL7685>. 

Isoquinuclidines 28 (aza-bicyclo [2.2.2]octanes) consist of IV-bicyclic structures which are the structural element of numerous natural occurring alkaloids with interesting biological properties (Sundberg and Smith 2002). Furthermore, these products can be readily converted to the biologically active pipecolic acids (Krow et al. 1982, 1999 Holmes et al. 1985). A retrosynthetic analysis shows that these isoquinuclidines 28 can be prepared from imines 29 and cyclohexenone 30 (Babu and Perumal 1998 Shi and Xu 2001 Sunden et al. 2005). 

Furthermore, the ring opening of the aziridinium salt 181, prepared from the aziridine 172 with methyl iodide at low temperature, by reaction with a number of nucleophiles also yielded the isoquinuclidine derivatives 182 predominantly, together with the isomer 183 (Scheme 35). 

HERG ("Human-ether-a-go-go related gene) at low concentrations. Conformationally constrained isoquinuclidine analogs of BRL-32872 were also prepared to study the effects of molecular flexibility towards class III and class IV anti-arrhythmic properties [48]. Both standard microelectrode and patch clamp assays indicated that while both epimers displayed a pharmacological profile similar to BRL-32872, epimer 52b was more effective than 52a. 

Extension560 of the potential566 of l,4,5,6-tetrahydro-3-acyl- or -3-alkoxy-carbonylpyridines to the preparation of the isoquinuclidine system of the lboga bases has not yet proved possible. 

Reduction of A-benzyl-3-cyanopyridinium bromide with sodium borohydride in aqueous solution containing -sodium carbonate gave a mixture of the yellow 1,2-dihydropyridine and colorless 1,6-dihydro-pyridine which was condensed with methyl vinyl ketone without purification to furnish the desired isoquinuclidine (XII) in 16% yield. Hydrolysis of the nitrile with cold concentrated hydrochloric acid afforded the amide identical with the adduct prepared by the reduction of l-benzyl-3-carboxamidopyridinium chloride followed by condensation of the crude mixture of reduced pyridines with methyl vinyl ketone. Reduction of the ketoamide with sodium borohydride gave a mixture of epimeric alcohols (XIII) which with sodium hypochlorite in methanol yielded one of the tricyclic urethanes (XIV) in a readily crystallizable... 

Bicyclic polyhydroxylated isoquinuclidines with conformations that mimic the boat-form of pyranosides have been prepared in multiple steps from an achiral pyridinone. These compounds proved to be strong and selective inhibitors of snail P-mannosidase (130 R = H, K 20 pm R = Bn, Ki 0.17 pm). ... 

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