Lingshuine, an Unexpected Passerini Product from the Hainan Sponge Axinyssa variabilis by Duo-Qing Xue a ), Ernesto Mollo b ), Guido Cimino b ), and Yue-Wei Guo* a ) a ) State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, P. R. China (phone: þ 86-21-50805813; e-mail: ywguo@mail.shcnc.ac.cn) b ) Istituto di Chimica Biomolecolare-CNR, I-80078, Pozzuoli (Naples) Lingshuine (1), a novel sesquiterpene amide, along with three known N-containing compounds, 2 – 4, have been isolated from the Hainan sponge Axinyssa variabilis . The structure of 1 was elucidated by detailed analysis of the spectroscopic data and by chemical methods. Lingshuine represents the first example of a Passerini product formed during the isolation process. Introduction. – Marine sponges of the order Halichondrida have proved to be a rich source of sesquiterpene isonitriles, isothiocyanates, and formamides [1 – 4]. These intriguing metabolites are thought to inhibit feeding by omnivorous browsers, but they do not deter nudibranchs that are specific predators on the sponges. The sponges of the genus Axinyssa (Order Halichondrida, Family Halichodriidae) have provided a diverse array of N-containing sesquiterpenes [5] since the first chemical investigation reported in 1989 by the Faulkner group [6]. In our previous publications [7] [8], isolation and structural determination of a series of mono- or dimeric bisabolene-type sesquiterpenes from the Hainan sponge A. variabilis were reported. Recently, a novel N-containing bisabolene-type sesquiterpene, named lingshuine (1), was isolated. Surprisingly, the isolate 1 is an artifact unexpectedly synthesized during the isolation process. To the best of our knowledge, this is the first case of a natural product-like compound from a natural resource. In this article, we wish to report isolation and structural elucidation of this uncommon new compound. Results and Discussion. – The usual workup [7][8] of the Et 2 O-soluble fraction from the acetone extract of the sponge yielded the new mixture 1 and related compounds 2 – 4, of which the structures were readily identified as theonellin formamide (¼ N-{trans-1-methyl-4-[ (2E,4E)-6-methylhepta-2,4-dien-2-yl]cyclohexyl}- formamide; 2) [9], 7-isocyano-7,8-dihydro-a-bisabolene (¼ (4R)-4-(2-isocyano-6-meth- ylhept-5-en-2-yl)-1-methylcyclohexene; 3) and 3-isocyanotheonellin (¼ trans-1-isocya- no-1-methyl-4-[(2E,4E)-6-methylhepta-2,4-dien-2-yl]cyclohexane; 4) [10], respective- ly, by analysis of the NMR data and by comparison with the data reported in the literature. The structural determination of 1 was not straightforward but somewhat challengeable because it was isolated as an inseparable complex mixture consisting of a sesquiterpene unit, and a hydroxy amide esterified with different long-chain (C 14 to C 20 ) fatty acids. Helvetica Chimica Acta – Vol. 92 (2009) 1428  2009 Verlag Helvetica Chimica Acta AG, Zürich