Axinella cannabina

The first marine isocyano metabolite was appropriately named axisonitrile-1 (1) based on the trivial name isonitrile and the genus of the sponge, Axinella cannabina, which also furnished axisothiocyanate-1 (2) [1] and, subsequently, a minor constituent, axamide-1 (3) [5]. This observation that isonitriles are often accompanied by isothiocyanates (-N=C=S) and formamides (-NHCHO) was later duplicated by the Hawaiian researchers working with a Halichondria sp. In... 

Axisonitrile-1 (1) and axisothiocyanate-1 (2) were the first pair of NC/NCS compounds isolated from Axinella cannabina, see Introduction [1]. That both compounds possessed a new skeleton was evident, when 1 was reduced (Li/EtNH2) to axane (6). Other transformations involving the exocyclic methylene which survived selective reduction (Na/NH3) of 1, coupled with evaluation of the lHNMR data, supported its gross structure. Confirmation of 2 was secured when 1 was heated with sulfur and the resultant purified product found to be identical to the natural product. 

About two dozen isocyano- and isocyano-related compounds with a eudesmane (12) skeleton are known. Although most of these were isolated from Axinella cannabina, the first isocyanoeudesmane, acanthellin-1 (14) [3], was obtained from a related sponge, Acanthella acuta, (cf. Table 2). Eudalene (13) resulting after two steps (i. Li/EtNH2, . Pd/C) from 14, proved the eudesmane skeleton. 

A minor isonitrile named acanthellin-2 with a specific rotation of — 24.1° was reported with no further details except some IR and MS data [3]. Isothiocyanate 15 and formamide 16 were also isolated from Axinella cannabina in a later study, in which isonitrile 14 and isomers 17-19 were also secured [35]. That 17-19 are C4(14)-ene isomers of 14 was concluded after extensive double resonance H NMR experiments. Coupling constants and nOe effects between the affected protons and various substituents of 17 established the relative stereochemistry of this series. 

Compounds 20-22 are further examples of minor metabolites of Axinella cannabina [40]. When Acanthella acuta was reinvestigated by the same researchers, isocyano compound 20, but not acanthellin-1 (14), was found to be the... 

The structures and relative stereochemistry of epi-eudesmanes 25-27 from Axinella cannabina were formulated from 2D NMR and chemical correlation experiments [36]. The 500 MHz HNMR spectrum of 1 l-formamido-7/ H-eudesm-5-ene (27) measured in CDC13 showed a 2 3 cis.trans ratio of the -NHCHO group (cis 3 8.06 d, J = 2 Hz trans 5 8.20 d, J — 12 Hz). Isothiocyanate 26 was one of several sesquiterpenes reported from Acanthella pulcherrima [20]. 

Fattorusso s group, which earlier had discovered 48-50 in Axinella cannabina, reported the occurrence of another spiroaxane series, 51 and 52, from Acanthella acuta. The habitat of the latter sponge is the Bay of Naples. As was the case with other metabolites reported in their recent studies, the investigators deduced the structures of isonitrile 51 and iso thiocyanate 52 chiefly by 2D NMR methods. 

Continued studies by the Naples group of Axinella cannabina resulted in another epimaaliane series of isocyano-related compounds, 73-75. Dehydrogenation of 73 with Pd/C at 350 °C afforded eudalene (13). The cyclopropyl moiety was evidenced by both proton and carbon resonances in the NMR spectra and relative stereochemistry was assigned by coupling constants and nOe data [52],... 

Sesquiterpenoids based on the axane skeleton (354) have been reported previously as metabolites of marine sponges or algae (cf. Vol. 5, p. 77 Vol. 6, p. 89). Further investigations in this area have revealed the presence of axisonitrile-4 (355), axisothiocyanate (356), and axamide-4 (357) in the sponge Axinella cannabina. These compounds are A -derivatives of known metabolites (axisonitrile-1 etc.) of this sponge and are included in this section because their biosynthesis may involve rearrangement of a eudesmane precursor. 

Isocyanide-containing natural products are rare they have been reported only from cyanobacteria, Penicillium fungi, marine sponges, and nudibranchs. Sesquiterpenoid and diterpenoid isocyanides are found in a limited species of sponges and nudibranchs that prey on these sponges. Axisonitrile-1 (106) isolated from Axinella cannabina is the first isocyanide-containing marine natural product. ... 

Conventional marine sterols have A -, A - or A Miene nuclei, but the occurrence of A -sterols was reported in Axinella cannabina [36]. Recently a complete analysis of sterols in the same species by Itoh et al. [37] showed the presence of 74 sterols with a variety of nuclei A , A, A , A, Sa-saturated and 5a-methoxy-... 

Compounds containing the isocyano group have fascinated natural products chemists ever since the first isocyanide xanthocillin was isolated from the fungus Penicillium notatum Westling in 1950 [1]. The existence of sesquiterpene isocyanides was first reported from the Mediterranean sponge Axinella cannabina in 1973 [2], closely followed by sesquiterpene isocyanides from the Mediterranean sponge Acanthella acuta by Minale et al. [3] and the Hawaiian sponge Halichondria sp. by Scheuer et al. [4]. These early reports also documented the presence of isothiocyanate [2] and formamide [4] functionality attached to the same carbon nucleus as the... 

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