Stemona alkaloid

Scheme 21 Threefold use of ruthenium catalysts in the first total synthesis of Stemona alkaloid tuberostemonine (113) [71]...

Several other twofold cyclization strategies have been developed by Smith and coworkers, ultimately to obtain access to the cyclic framework of penitrem D with the correct stereochemistry [176]. Williams group has been interested in Stemona alkaloids, which are represented by approximately 50 structurally novel, polycyclic natu-... 

Quite recently, a domino Diels-Alder/Prins/pinacol reaction was reported by Barriaulfs group [38]. This novel method is very reliable and efficient for the synthesis of highly functionalized bicyclo[m.n.l]alkanones. In addition, Aube and coworker [39] used a combination of a Diels-Alder and a Schmidt reaction within the total synthesis of the Stemona alkaloid stenine [40]. 

In the synthesis of the azabicyclic core of the Stemona alkaloids, methyl (2/W,3.9/ ,3a/W)-2-(2-cthoxycarbonylethyl)-hexahydropyrrolo[l,2- ]isoxazole-3-carboxylate was hydrogenolyzed over 10% Pd-C in EtOAc and acetic acid at room temperature to give after cyclization the bicyclic lactam 153 <2005JOC3157> (Equation 22). This route was also used to produce pyrrozilidinone-based dipeptide isosteres <2005T8836>. 

Several isoxazolidines or their quaternary salts derived from the 1,3-dipolar cycloaddition of rr/i-hcxcnolidcs (6,7-dihydrooxepin-2(5//)-ones) to cyclic nitrones, were converted into the corresponding piperidyl- and pyrrolidyloxepi-nones by reduction of the nitrogen-oxygen bond (Equation 4). These amino alcohols provide a new access to the l-azabicyclo[5.3.0]decane core of the Stemona alkaloids <2004EJ04215>. 

An interesting approach toward the total synthesis of the Stemona alkaloid, (-)-stenine (25), which have been used in Chinese and Japanese folk medicine as insecticides, as drugs for the treatment of respiratory diseases, via spirolactone... 

The stemona alkaloid stemonamide (49) was synthesized starting from a-stannyl acetate 47 and 2-stannyl pyrrolidine 48. The oxidative coupling of stannyl acetate 47 with acetylenic silyl enol ether affords the functionalized C-7 unit which corresponds to the side arm of the pyrrolidine ring. Then, introduction of the C-7 unit to the pyrrolidine ring is performed by the oxidative generation of acyliminium ion. The carbon skeleton of stemonamide was thus constructed efficiently as shown in Scheme 19 by employing organotin compounds. ... 

A new Stemona alkaloid sessilifoliamide C, 41 (from Stemona sessilifolia) has been described with a fused azepine skeleton a butanolide analogue (sessilifoliamide B) was also isolated <03T7779>. 

The synthesis of (—)-stemospironine provides another example of the use of aziridinium ions in natural product synthesis <20010L2721>. The Stemona alkaloids are characterized by the l-azabicyclo[5.3.0]decane nucleus. Azide 363 was the key intermediate for the aziridinium-mediated synthesis. Debenzylation at low temperature... 

The Stemona alkaloids were reviewed over a decade ago (Volume V, p. 323) at which time there was both confusion as to the number of alkaloids and contradictory evidence bearing on their structure. Two apparently new alkaloids have since been described and the structure of tuberostemonine has been elucidated. 

A synthetic strategy was developed for the typical core structure of the Stemona alkaloids in the laboratory of C.H. Heathcock. " The precursor for the 1-azabicyclo[5.3.0]decane ring system was prepared via the successive double alkylation of the dianion of ethyl acetoacetate. 

During the endgame of the total synthesis of the stemona alkaloid (-)-stenine, Y. Morimoto and co-workers utilized the Finkelstein reaction to prepare a primary alkyl iodide from a primary alkyl mesylate. The mesylate was prepared from the corresponding primary alcohol with MsCI/EtsN. The resulting primary alkyl iodide was used in the subsequent intramolecular N-alkylation to construct the final perhydroazepine C-ring of the natural product. 

The total synthesis of Stemona alkaloid (-)-tuberostemonine was accomplished by P. Wipf. Late in the synthesis, the introduction of an ethyl sidechain was required. This could be achieved in a novel four-step sequence. First, the allyl sidechain was introduced by the Keck radical allylation. To this end, the secondary alkyl phenylselenide substrate was treated with allyltriphenyltin in the presence of catalytic amounts of AIBN. This was followed by the introduction of a methyl group onto the lactone moiety. The allyl group then was transformed into the desired ethyl group as follows the terminal double bond was isomerized to the internal double bond by the method of R. Roy. This was followed by ethylene cross metathesis and catalytic hydrogenation to provide the desired ethyl sidechain. 

The first total synthesis of the Stemona alkaloid (-)-tuberostemonine was accomplished by P. Wipf and co-workers. " The installation of the butyrolactone moiety commenced with the preparation of a Weinreb s amide from a methyl ester. The tricyclic methyl ester substrate was exposed to A/,0-dimethylhydroxylamine hydrochloride and Me2AICI and the tertiary amide was isolated in excellent yield. Next, the bromo ortho ester was treated with LDBB in THF to generate the corresponding primary alkyllithium species, which cleanly and efficiently added to the Weinreb s amide to afford the desired ketone. 

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