Sceptrin

A recent publication by the group of Baran reports the total synthesis of ageli-ferin, an antiviral agent with interesting molecular architecture (Scheme 4.16) [42], Just 1 min of microwave irradiation of sceptrin, another natural product, at 195 °C in water under sealed-vessel conditions provides ageliferin in 40% yield, along with 52% of recovered starting material. Remarkably, if the reaction is performed without... 

The Baran group has reported an unusual deprotection of allyl esters in micro-wave-superheated water. A diallyl ester structurally related to the sceptrin natural products (see Scheme 6.87) was cleanly deprotected at 200 °C within 5 min (Scheme 6.168) [181]. Other standard deprotection transformations carried out under microwave conditions, specifically N-detosylations [317], trimethylsilyl (TMS) removal [318, 319], and N-tert-butoxycarbonyl (Boc) deprotection [231], are summarized in Scheme 6.169. 

Baran PS, Li K, O Malley DP, Mitsos C (2006) Short, Enantioselective Total Synthesis of Sceptrin and Ageliferin by Programmed Oxaquadricyclane Fragmentation. Angew Chem Int Ed 45 249... 

Scheme 31 Microwave-assisted formation of Ageliferin from Sceptrin...

The authors irradiated a sample of Sceptrin in water at 195 °C for 1 min, using a dedicated monomode microwave apparatus. They investigated the process in detail and found that after a series of tandem tautomerizations and [1,2] shifts, Scerptin did indeed convert into the structural analogue Ageliferin. They further confirmed the reaction and mechanistic details by deuterium-labeling. 

Maleic anhydride (117) belongs to the first compounds, the [2 + 2]-photocycloaddi-tion reactions of which were extensively explored [112]. It is preferably converted to the corresponding cyclobutanes by irradiation in the presence of a sensitizer, for example, benzophenone, allowing the addition of a plethora of alkenes (Scheme 6.42). In a recent application the photocydoaddition product 118 of maleic anhydride and l,4-dichloro-2-butene was converted into the marine alkaloid ( )-sceptrin (119) [113]. 

The fungicidal activity of sceptrin at 10 ppm was found to be >65 % inhibition of Phytophthora infestans (potato late blight) [103]. In addition to its antimicrobial, antiviral [104], antimuscarinic [22], and antihistaminic [30] properties, sceptrin was shown to be the first and most potent nonpeptide somatostatin inhibitor in the submicromolar range [105]. 

Despite its potent biological activity, sceptrin remained a prominent unanswered synthetic challenge until 2004. Although upon cursory inspection it appears to be a photodimer of hymenidin, synthetic strategies involving the dimerization of 2 have been futile. The first short total synthesis of sceptrin in its racemic form was... 

Sceptrin has also been found in several different sponges, co-occurring vith related compounds. Oxysceptrin (67), previously found by Rinehart et al. in a sample of Agelas conifera [109], vas re-isolated by Kobayashi et al. together vith sceptrin from the Okinawan sponge Agelas cf nemoechinata [110]. Its activity as an actimyosin-ATPase activator has been reported [110]. 

Numerous antiviral and antibacterial sceptrin/oxysceptrin derivatives (68-72), along with the diacetate salts of sceptrin and oxysceptrin, were isolated from Agelas conifera [104,111,112]. 

Two sceptrin-related compounds, nakamuranic acid (73) and its corresponding methyl ester (74), have been isolated from the Indo-Pacific sponge Agelas nakamurai [114,115],... 

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