4 -Frangulanine-type cyclopeptide

D (48), were elucidated mainly through homo- and heteronuclear NMR techniques (45). Two new 14-membered frangulanine-type cyclopeptide alkaloids, lotusanines A (38) and B (59), have been isolated from the aerial parts of Z. lotus, together with the known alkaloids sanjoinenine (60), sanjoinine F (40), and frangufoline (41) (46). Four new cyclopeptide alkaloids, lotusines B (46), C (47), E (19), and F (20), were isolated from the root bark of Z. lotus. Their structures were elucidated mainly by homo-and heteronuclear NMR techniques (47). 

It has already been mentioned that in 4(14)-frangulanine-type cyclopeptide alkaloids R is the P-OH-Leucine side chain, while in 4(14)-integerrine-type cyclopeptide alkaloids R is the P-OH-Phenyla-lanine side chain. This leads to the generalization shown in Table 5. 

Ceanothines B, C and D which belong to the category of 4(14)-frangulanine-type cyclopeptide alkaloids, bear NMePro as basic terminal amino acid. In this case a = a (m/z = 84), while fragments b, n, o and p are absent. 

This alkaloid contains a unique structure. It is comprised of five units, four of them being attached to one side of the aminophenol, the fifth unit. The ring-bound amino acid bears an additional basic terminal amino acid. According to Marchand et al. (62) the fragments that are encountered are i (m/z=135), a and o (mlz = S6 and 58 respectively). They originate from one basic terminal amino acid (N-Me-L-Val) in accord with the fragmentation behaviour of 4(14)-frangulanine-type cyclopeptide alkaloids. 

Fig. 2. Main fragments of 4(14)-frangulanine- and -integerrine-type cyclopeptide alkaloids...

Table 5. m/z Values of Fragments of 4(14)-Frangulanine- or -Integerrine-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. 

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 reported synthesis of frangulanine (166), the major representative of this type, constitutes the first total synthesis of a 4(14)-membered cyclopeptide alkaloid. This synthesis (>26 steps in an overall yield of ca 0.30%), starting from (25,35)-2-hydroxymethyl-3-isopropyloxirane, comprises the preparation of a oxazolidinone derivative, subsequently conversed to the corresponding aryloxy compound, the coupling of the (Z)-leucine, the ring closure, the installation of the insaturation of the styrylamine unit and, finally, the insertion of the (5)-MA -dimethyliso-leucine moiety. 

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