Stemona alkaloids structure

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-... 

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. 

There are six species of stemona plants growing in China Stemona tuberosa Lour. St. sessilifolia (Miq) French, et Savat, St. japonica (Blume) Miq., St. parviflora C.H. Wright, St. mairei Levi and Croomia japonica Miq. The first three plants are used in TCM and the latter three are used in folk medicine as insecticide, too. In the past, eleven stemona alkaloids have been separated from the roots of the first three Stemona plants and their structures were determined mostly by X-ray crystallography analyses due to the complexity of these structures. (Table 7 and Scheme 15) [58,59]. There are also several other stemona alkaloids, which have been reported, but their structures are unknown. 

In early 1949 Chinese chemist prof. Zhu Ren-hong started to study on stemona alkaloids from the roots of Stemona sessilifolia and separated an alkaloid, identified as stemonidine [60], which was separated by Suzuki from St. japonica in 1929, its structure, however, was not clear at that time [61]. In 1981, this study was continued and the structure of stemonidine 8-34 was determined by using spectral analyses with the modern 2D-NMR technique. Later it was found, that the structure of stemonidine is similar to stemospironine, isolated from St. sessifolia by Sakata in 1978 and determined its structure by X-ray crystallography [62,63]. At the same time, the structures of two new sterioisomer alkaloids, stemotinine 8-35 and isostemotinine 8-36, were studied. Both alkaloids were isolated... 

From the above structures we noticed all of stemona alkaloids contain a 4-azaazulene or perhydroazaazulene ring and most of them have a-methyl-y-lactone ring linked at C-3 position, which can be detected by IR absorption at around 1760 cm-1, characteristic mass peak at M+ - 99 (M+ -C5H7O2) and doublet methyl signal at around 81.20. Some of these alkaloid structures contain another a-methyl-y-lactone ring in its left side. 

Stemona alkaloids. Root extracts of the medicinal plants Stemona japonica and S. tuberosa (Stemona-ceae) have been used in Chinese and Japanese folk medicine as insecticides, anthelmintics, and as drugs for the treatment of tuberculosis, bronchitis and pertussis. Responsible for the activities is a group of more than 20 polycyclic alkaloids with diverse structures, e.g. protostemonine CjsHsiNOj, Mr 417.50, mp. 172-173 °C, [alD +148° (CH3OH) and stemofoline. 

Intramolecular variants are the most common type of Diels-Alder reactions employed in total syntheses with carbocycles the most popular targets. Among the broad variety of structures in this class, bicyclic decalin structures, both cis and trans, are readily available on intramolecular Diels-Alder reactions. Aube demonstrated the use of a tandem intramolecular Diels-Alder/Schmidt reaction sequence in his synthesis of three stemona alkaloids. The first steps generates cw-decalin intermediate 124, which undergoes a ring expansion in the Schmidt reaction to furnish tricycle 125. ° ... 

The Stemona alkaloids are structurally characterized by the presence of either an exposed or hidden pyrrolo[l,2-a]azepine (k=1) moiety (5), also named perhydro-azaazulene (12) or 4-aza-azulene (13), or a pyrido[l,2-a]azepine (n = 2) nucleus (A, Fig. 1) and currently comprises 68 alkaloids. 

Xu and coworkers have previously suggested that the Stemona alkaloids can be separated into eight structural groups according to the sites of connection between the... 

The stemofoline group comprises some of the structurally more complex representatives of the Stemona alkaloids, and currently ten alkaloids have been described stemofoline (48) 17,22,53,54), oxystemofoline (49) (77), methoxystemofline (50) (77), 2 -hydroxystemofoline (51) 22,36), 16,17-didehydro-16( )-stemofoline (52) 22,54), also named as didehydrostemofoline, l, 2 -didehydrostemofoline or asparagamine A (5,55),... 

The first total synthesis of stemospironine (30), a structurally complex Stemona alkaloid, was accomplished by Williams and coworkers (75) (Scheme 18), using the same strategy successfully applied by the same group for the total synthesis of croomine and... 

The elucidation of the complex structures of the Stemona alkaloids involved mainly H and C-NMR, and X-ray analysis (Section II). 

Stemofoline is an insecticidal alkaloid produced in the leaves and stems of the plant Stemona japonica. It has a good spectrum of activity, with rapid action, and is a potent agonist of the nicotinic acetylcholine receptor in insects. These features make it a promising lead, except that its highly complex polycyclic structure is a real challenge for synthesis (Figure 3). 

More than 130 alkaloids from various species of the genus Stemona are known in the literature, and different classification are also reported [6], Structurally, the alkaloids are characterized by a pyrrolo[l,2-a]azepine nucleus usually linked with two carbon chains mostly forming terminal lactone rings. 

Sakata, K., K. Aoki, C. Chang, A. Sakurai, S. Tamura, and S. Murakoshi, Stemospironine, a new insecticidal alkaloid of Stemona japonica Miq. Isolation, structural determination and activity, Agric. Biol. Chem., 42, 457-463 (1978). 

Isostenine (3) has been isolated from S. collinsae, an indigenous Stemona species from Vietnam, the structure of which was established mainly by NMR spectroscopy 20). An alkaloid later isolated from S. tuberosa in a bioactivity-directed phytochemical analysis was named neostenine and the same structure as isostenine (3) was proposed (2). Although the same structure has been assigned to these two alkaloids, inspection of their physical [isostenine mp 213-215°C (ref. 20, experimental section), [q ]d = +92° (CHCI3, c = 0.6) neostenine mp 90-92°C, [a]D =-1-73.6° (MeOH, c = 0.1)] and spectroscopic data ( H- and C-NMR) does not support their identity and a structural reinvestigation seems to be in order. 

The first alkaloid to be reported was stemocurtisine (58), isolated from the roots of 5. curtisii, the structure of which was established by X-ray crystallography. The piperidine ring adopts a chair-hke conformation, and it displays an ether bridge involving Cl and C9. The acetal-like nature of C9 is confirmed by the presence of a signal at 120.5 ppm in its C-NMR spectrum. The absolute configuration is not known, but it is assumed to be the same as the one in those alkaloids with the same C/D ring substructure [stemofoline (48)] (57). The same alkaloid was also isolated from the roots of Stemona sp. (56). 

The second chapter is on a group of alkaloids, the Stemona, which, considering its overall size, possesses a remarkable number of complex alkaloid skeleta. This area was last reviewed in 1967, and the tremendous changes in this field are presented by Pilli, Rosso, and de Oliveira, from the perspectives of their isolation, structure determination, and biological activity. 

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