Nummularine

Nummularine-A He Leu Monomethyl Phe CseH sNsOe 047 235-240° — 397° (CHCI3) Zizypkus nummularia Rhamnaceae 4... 

The first total synthesis of the 14-membered para ansa cyclopeptide alkaloid (-)-nummularine F was accomplished in the laboratory of M.M. Joullie. The A/3 nitrogen atom was introduced by using the Henry reaction between the 4-formylphenoxy group and the anion of nitromethane, followed by reduction of the nitro group to the corresponding amine. The epimeric benzyl alcohols did not pose a problem since they were dehydrated at the end of the synthetic sequence to give the C1-C2 double bond. 

A number of new 14-membered-ring alkaloids incorporating the p-hydroxy-styrylamine and j8-hydroxyphenylalanine structural features have been isolated and structurally elucidated, mainly by application of high-resolution mass spectrometry. Cre natine A (55) has been obtained from Discaria crenata while alkaloid A, (feretine) (56) and alkaloid A2 (57) have been isolated from Feretia apondanthera. In addition to four known alkaloids, the root bark of Zizyphus nummularia has yielded nummularine-D (58) and nummularine-E (59). ... 

Nummularine-F (60) and zizyphine-G (61), elaborated by Z. nummularia and Z. oenoplia respectively, represent the only new additions to the 14-membered-ring alkaloid class which exhibit the p-hydroxystyrylamine and 3-hydroxyproline units as characteristic features. The known cyclopeptide mauritine-A, together with minor amounts of amphibines-A, -E, and -F, and mauritine-C have been isolated from Z. spinachristi of Nigerian origin. ... 

From Zizyphus nummularia, in addition to the known alkaloid nummu-larine B (7), two new peptide alkaloids nummularine M (36) and nummular-... 

N-Acetyl-L-tryptophan has been found d in Claviceps purpurea PRL 1980 cultures. Nb. b-Dimethyltryptophan is one of the constituent amino-acids in the peptide alkaloid nummularine-K (c/. Chapter 15). 

Ziziphus nummularia also produces fourteen-membered-ring cyclopeptides nummularines G and K, obtained from its bark, have been assigned structures (22) and (23) respectively," and they are accompanied by the thirteen-membered-ring compound nummularine H (24), i.e. N-desmethyljubanine A."... 

We would like to stress that several cyclopeptide alkaloids have been recorded as new compounds without mention of or reference to previously isolated compounds possessing identical chemical structures. Some of the newly isolated cyclopeptide alkaloids must be identical with or stereoisomers of older ones. Therefore, daechuine-SlO (15) is superficially identical with nummularine-R (14), daechuine-S5 (47) with melonovine-A (46) or pubescine-A (45), lotusanine-A (63) with adouetine-Y (= myrianthine-B) (62), discarine-X (73) with nummular-ine-K (74), discarine-D (97) with crenatine-A (96) and AM-2 (95) with... 

There are four cyclopeptide alkaloids containing an iV-formyl basic terminal amino acid. Three of them, nummularine-T, rugosanine-A and sativanine-F, are 5(13)-zizyphine-A-types and sativanine-K is a 4(13)-nummularine-C-type. From these alkaloids fragment a has the usual structure, having the formyl residue as an N-substituent, and is not the base peak. The last corresponds to fragment a, which gives birth to a and a" (Fig. 24) (52, 54, 56, 68). 

Derivatives A/-Methyl-dihydro-nummularine-B = Dihydro-amphIblne-H (76) N-Formyl-nummularine-B (52)... 

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