Pandamine

In 1963 a group of Swiss authors (12) isolated zizyphine from Zizyphus oenoplia and recognized isoleucine and proline as components. Two years later Zbiral etal. (13) proposed a complete structure which was later revised (14). Pais et al. (15) in an earlier preliminary report suggested the structure of pandamine which had been isolated from Panda oleosa. This was confirmed in 1966, and the structure of the similarly constituted pandamine was reported (17). Shortly thereafter Tschesche and co-workers (18) reported the structure of an alkaloid of this type scutianine-A from Scutia buxifolia. Since then the number of cyclopeptide alkaloids of known structure has risen to more than sixty, a figure which Klein and Rapoport had envisioned in 1968 (20). The workers at Gif-sur-Yvette and at Bonn have been in the forefront of these researches but others have made important contributions (19-26). 

There are several peptide alkaloids which do not fit the above described classification, namely, pandamine (56), pandaminine (57), hymenocardine (58), and lasiodine-A (59). The determination of their structures has already been referred to (3, 4) and is briefly outlined here. It was largely consequent upon chemical degradation in part because the mass spectral fragmentation patterns had not been worked out and in part because such analyses of the alkaloids or their derivatives do not, or only partly, lend themselves to the study of such fragmentation schemes as are described in Section VII. 

Exhaustive NMR spectral studies have been reported for ceanothine-B(i9, 24-26), for pandamine (17), for americine (20), for aralionine-A (31), and their derivatives. The number and type of NMe and OMe groups can be learned as can the number and position of the amide NH protons even though exchange with deuterium is not always straightforward. In examples in which mass spectra do not differentiate between leucine and isoleucine the NMR spectra sometimes can do so. 

Two brominated linear peptides that are found in the sponge Cliona celata, celenamide A (21 R = CH2CHMe2) and celenamide B (21 R = CHMe2), bear close structural relationships to the cyclic peptides integerrin and lasiodine A that occur in plants.16 A I3C n.m.r. analysis of cyclic peptide alkaloids has been reported and the chemical shifts of most of the carbon atoms in discarines A and B, lasiodines A and B, pandamine, pandaminine, and hymenocardine have been assigned.17... 

Early studies on one of the plants, Ceanothus americanus, showed the alkaloid fraction to be a complex mixture of closely related compounds, as has since been found to be true for most of the other plants examined. Little real progress in the chemistry of these compounds was possible until the recent development of the more refined separation and analytical techniques of thin-layer chromatography, n.m.r., and organic mass spectroscopy. The structures of the first few bases (pandamine, zizyphine, ceanothine-B, scutianine, and the adouetines ) were determined by a combination of chemical degradation and applied spectroscopy. More recently, automatic amino-acid and mass spectroscopic analysis of these... 

Within the 4(14)-compounds is the group of pandamine type compounds (8 compounds total) which contain a 2-alkoxy-2-(p-hydroxyphenyl)-ethylamine D unit, instead of styrylamine. Among the 5(14) compounds hymenocardine contains valine as the B unit and a 2-alkoxy-2-(p-hydro-xyphenyl)ethylamine D unit, instead of styrylamine. 

Common fragments are fragments that give no information about R, R R R and R but confirm the nature of the aminophenol moiety. Furthermore their occurrence is indicative of 4(14) cyclopeptide alkaloids. Fragment u and common fragments with mh 120, 107 and 103 are more frequent for the 4(14)-pandamine types. 

Mass spectra of 4(14)-Pandamine-type cyclopeptide alkaloids contain all the fragments previously described and in addition fragments b", f and i (Fig. 5, Table 6). These last fragments are related to... 

Fig. 5. Special fragments of 4(14)-pandamine-type alkaloids Table 6. m/z Fragments of 4(14)-Pandamine-Type Cyclopeptide Alkaloids...

The main fragmentation pattern of this category follows that of the 4(14)-frangulanine-, -integerrine- and -pandamine-type cyclopeptide alkaloids and exhibits the same a-m and q-v fragments. 

Scutianene-C and sanjoinenine afford the following 4(14)-frangula-nine-, -integerrine- and -pandamine-type fragments e, f, h, i, 1, m, q, x, y and z. 

Lotusanine-B displays the following 5(14)-scutianine-A-type fragments e, f, i, m, q, q". In addition, fragments x, x-CO, y, y-CO of 4(14)-frangulanine-, -integerrine- and -pandamine-type cyclopeptide alkaloids appear. Finally fragments n and o, analogues of n and o of 5(14)-amphibine-B-type cyclopeptide alkaloids occur (Fig. 22). 

The total synthesis of sanjoinine-Gl, a 4(14)-pandamine-type cyclopeptide alkaloid, was achieved in 17 overall steps (1.36% overall yield) starting from D-serine (767). A novel synthetic protocol was developed, including highly diastereoselective synthesis of the (5,5)- -phenoxyleucine unit. 

Pais, M., F.-X. Jarreau, X. Lusinchi, and R. Goutarel Alcaloides Peptidiques, III (I). Pandamine et Pandaminine, Alcaloides du Panda oleosa Pierre (Pandacees). Ann. 

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