Quinolizidine lactone

When pyridinium salt 187 was transformed to an indolo[2,3-a]quinolizidine compound in a similar way and the unsaturated lactone 188 was hydrogenated over platina catalyst, a mixture of vallesiachotamine-type compounds (189 di-astereomers) epimeric at C-20 was formed (134). These compounds have also been prepared in optically active form from vallesiachotamine (9), thus producing the first chemical correlation between synthetic and natural vallesiachotamine derivatives (134). 

An X-ray study of vertaline hydrobromide established the structure and absolute stereochemistry of vertaline as shown in 51 (32, 43). The relative stereochemistry at C-l and C-3 in all alkaloids in the group is the same as in the biphenyl alkaloids for example, the biphenyl ether and lactone group are linked to the quinolizidine ring in axial and equatorial configurations, respectively. 

Two lactonic arylquinolizidine alkaloids, vertaline (61) and decaline (62), which possess a diphenyl ether moiety have been synthesized (20-22). The former alkaloid has a m-quinolizidine ring, while the latter possesses a trans-quinolizidine structure. Unnatural 17-O-methyllythridine (63), a derivative of lythridine (64), was synthesized utilizing a new strategy for macrolide cycliza-tion (23). 

Although a number of alkaloids belonging to the simple arylquinolizidine class and the lactonic type had been synthesized, no successful synthesis of cyclophane alkaloids was accomplished until that of lythranidine (94), a unique alkaloid with a 2,6-trans disubstituted piperidine structure, was reported (28, 29). Quinolizidine metacyclophane alkaloids lythrancepines II (95) and III (96) have also been synthesized recently (30, 31). A review on the synthesis of lythranidine (94) is available in Japanese (32). 

When the unconjugated amino lactone 12a, previously obtained as a degradation product of securinine (Scheme 1), was heated under reduced pressure the isoquinuclidine 53 was obtained in low yield (Scheme 9) (29). This rearrangement appears not to have had any significance in the structural elucidation of securinine but it has intrinsic chemical interest and thus will be discussed separately here. The IR spectrum of 53 shows bands at 2821, 2721, and 2681 cm , representative of a m is-quinolizidine structure and at 1794, 1735, and 1644... 

New reactions of isoquinoline derivatives include the following 3,4-di-hydroisoquinoline N-oxide with 2-acetylcycloalkane-l,3-diones, Reissert compounds with stilbene and tolan derivatives, isoquinoline with pyrrole derivatives and with 2-methylfuran " (both in the presence of benzyl chloride), and the chromium trioxide oxidation of the benzo[a]quinolizidine (49) to give (50). Compound (49) was prepared by the condensation of 3,4-dihydroiso-quinoline with the 5-lactone (51). Further examples of a classical benzo[a]-... 

Nucleophilic species derived from treatment of lactones and anhydrides with base can also react with 3,4-dihydroisoquinolines or with 1-chloroquinolines to give quinolizidines. Two examples of the application of this methodology to the preparation of berberine derivatives (272) and (273) <84LA389> are shown in Equations (31) and (32). 

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