Asymmetric Synthesis of the Azabicyclic Core of the <i>Stemona</i> Alkaloids

Alibés, Ramón; Blanco, Pilar; Casas, Eva; Closa, Montserrat; March, Pedro de; Figueredo, Marta; Font, Josep; Sanfeliu, Elena; Álvarez‐Larena, Ángel

doi:10.1021/jo047867q

Cited by 31 publications

(14 citation statements)

References 75 publications

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“…All these provenances were dominated by derivatives showing a close structural relationship to tuberostemonine (1). Beyond that, a series of spiro derivatives was also described [2], which were closely related to stemoninine (21) (Fig. 3).…”

Section: Stemona Tuberosa Complexmentioning

confidence: 93%

“…The well-known tuberostemonine (1) and its closely related derivatives tuberostemoenone (18), tuberostemoninol (19), oxotuberostemonine (24), and stenine (26) can be derived by linking C-12 of the lactone ring with C-1 of the pyrroloazepine core, whereas in parvineostemonine (38) an unusual linkage between C-11 and C-3 can be observed. The formation of an ether bridge between C-11 and C-8 leads to the spiro system of stemoninine (21), and another between C-12 and C-16 to the structure of parvistemonine (35). The unusual six-membered piperidone ring of tuberostemoninol (19) can be explained by opening the bond between C-1 and C-9a of tuberostemonine (1) and linking C-1 with C-9.…”

Section: Stichoneurine (Tuberostemonine-)-type Alkaloidsmentioning

confidence: 99%

“…They were named bisdehydrostemoninine ( = didehydrostemoninine) (22), stemoenonine (23) [2] and stemoninoamide (28) [64]. The original description of stemoninine (21) for S. sessilifolia [49], [67] can most likely be explained by a confusion with S. tuberosa [2].…”

Section: Stemona Tuberosa Complexmentioning

confidence: 99%

“…The intricate structures of these alkaloids, sometimes leading to very complex cage-type molecules, have already attracted considerable synthetic interest. They served as a stimulus for the development of new strategies for the construction of the skeleton as well as for successful total syntheses of a number of derivatives e. g., [19], [20], [21]. In a previous review 42 naturally occurring derivatives were listed mostly isolated from the tuberous roots of the genus Stemona [1].…”

Section: Introductionmentioning

confidence: 99%

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Structural Relationships, Distribution and Biological Activities ofStemonaAlkaloids

2006

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Stemona alkaloids represent a unique class of natural products exclusively isolated from the monocotyledonous family Stemonaceae comprising three genera mainly distributed in southeast Asia. Structurally the alkaloids are characterised by a pyrrolo[1,2-a]azepine nucleus usually linked with two carbon chains mostly forming terminal lactone rings. Based on biosynthetic considerations and their various distribution the present review describes 82 Stemona alkaloids grouped into three skeletal types. Due to different carbon chains attached to C-9 of the pyrroloazepine nucleus they were classified into stichoneurine-, protostemonine-and croomine-type alkaloids. The genera Croomia and Stichoneuron only accumulate croomine or stichoneurine derivatives, respectively, whereas the genus Stemona produces all three types of alkaloids. However, species-specific accumulation trends towards certain structural types represent valuable chemosystematic criteria. Bioassays with larvae of Spodoptera littoralis exhibited very high insect toxicity for the roots of Stemona species containing certain protostemonine derivatives, especially didehydrostemofoline, whereas those with dominating stichoneurine or croomine derivatives showed low toxicity but sometimes remarkable repellence due to an accumulation of tuberostemonine. Tuberostemonine also showed effects on the motility of helminth worms and reduced the excitatory transmission at the crayfish neuromuscular junction. Significant antitussive activity was shown for the stereoisomeric neotuberostemonine in guinea-pig after cough induction by citric acid aerosol stimulation. Studies on structure-activity relationship with seven related compounds revealed that the saturated tricyclic pyrrolobenzazepine nucleus of tuberostemonines is the prerequisite for antitussive activity.

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Section: Stemona Tuberosa Complexmentioning

confidence: 93%

Section: Stichoneurine (Tuberostemonine-)-type Alkaloidsmentioning

confidence: 99%

Section: Stemona Tuberosa Complexmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Structural Relationships, Distribution and Biological Activities ofStemonaAlkaloids

2006

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“…Essential for the success of our approach was the efficient preparation of the initial nitrone in enantiopure form, and so we developed the syntheses of nitrones 84 / 85 ,95,110a 88 ,110b and 91 ,88b,110c starting from L ‐prolinol, ethyl L ‐pyroglutamate, and D ‐glyceraldehyde, respectively (Scheme ). Out of these syntheses, the oxidation of the TBDPS derivative of prolinol with oxone is at the moment the most practical one, but nitrone 91 contains an additional stereocenter and suitable functionalization for the installation of the alkaloid “east”‐side lactone when required.…”

Section: Synthetic Strategies In the Stemoamide And Tuberostemospimentioning

confidence: 99%

Strategies for the Synthesis of Stemona Alkaloids

Alibés

Figueredo

2009

Eur J Org Chem

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Keywords: Stemona alkaloids / Natural products / Synthesis design / Synthetic methods / AlkaloidsThe extracts of several plants of the Stemonaceae family have long been used in Asian countries against different diseases and for their antiparasitic properties. Significant constituents of these extracts are a series of structurally related secondary metabolites named Stemona alkaloids. All the Stemona alkaloids are polycyclic and contain multiple stereocenters. Most of them present a central pyrrolo[1,2-a]-azepine system and the majority also incorporate at least one α-methyl-γ-butyrolactone substructure. Their challenging molecular architectures have motivated the development of new strategies for the construction of their skeletons, but

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The Barton‐McCombie Reaction

2012

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Deoxygenations of alcohols, i.e., processes that replace a hydroxyl group with hydrogen at a saturated carbon, find applications in both total synthesis and the systematic modifications of natural products. They may also be employed to introduce deuterium or tritium in a site‐specific manner. Reductive methods that involve ionic or highly polarized reagents or intermediates can be limited in their applicability: for example, competing reaction pathways including cationic rearrangements and anionic eliminations may be encountered in sterically hindered systems with substrates bearing heteroatoms close to the center undergoing reduction. As evidenced by developments over the last few decades, methods that involve the generation and direct quenching via hydrogen atom abstraction of the derived, carbon‐centered radical typically show the greatest tolerance for the presence of other functional groups and for variations in both the steric acid and the electronic environment in the vicinity of the center undergoing deoxygenation. Derivatization of the hydroxyl is a prerequisite, the determinant factors for efficient formation of the deoxygenated product lies in the ability of the combination of the substrate and reagents to induce homolysis of the C‐O bond coupled with the induction of homolysis to rapidly reduce a free radical by hydrogen donation, thereby propagating an efficient chain process. A high‐yielding way to realize this sequence was first described by Barton McCombie using the free‐radical chain reaction of O ‐thioacyl derivatives of secondary alcohols with tri‐ n ‐butylstannane. This chapter provides a detailed description and comparison of the combinations of substrates and reagents that will bring about these processes and provides a summary and evaluation of alternative deoxygenation methods. Mechanistic and stereochemical issues set out the scope and limitations of these processes with respect to both the thioacylation and reduction steps and exemplify some applications to both total synthesis and the modification of natural products.

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Asymmetric Synthesis of the Azabicyclic Core of the Stemona Alkaloids

Cited by 31 publications

References 75 publications

Structural Relationships, Distribution and Biological Activities ofStemonaAlkaloids

Structural Relationships, Distribution and Biological Activities ofStemonaAlkaloids

Strategies for the Synthesis of Stemona Alkaloids

The Barton‐McCombie Reaction

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