Indolizidine and quinolizidine alkaloids

This review covers the isolation, structure determination, synthesis, chemical transformations and biological activity of indolizidine and quinolizidine alkaloids. Included in the review are the hydroxylated indolizidines lentiginosine, swainsonine, castanospermine and their analogues; alkaloids from animal sources, including arthropods and amphibians; alkaloids from the genera Polygonatum, Prosopis and Poranthera; phenanthroindolizidine and phenanthroquinolizidine alkaloids; Nuphar alkaloids; lupine alkaloids; and alkaloids from marine sources. 130 references are cited.     

Indolizidine and quinolizidine alkaloids

This review covers the isolation, structure determination, synthesis, chemical transformations and biological activity of indolizidine and quinolizidine alkaloids from microbial, plant and animal sources. Included in the review are the hydroxylated indolizidines lentiginosine, swainsonine, castanospermine and their analogues; alkaloids from animal sources, including ants, amphibians and beetles; ipalbidine, phenanthroindolizidines and related alkaloids; Lycopodium alkaloids; lupine alkaloids; and alkaloids from bacterial and marine sources. The literature from July 2002 to June 2003 is reviewed, and 174 references are cited.     

Indolizidine and quinolizidine alkaloids

This review covers the isolation, structure determination, synthesis, chemical transformations and biological activity of indolizidine and quinolizidine alkaloids from microbial, plant and animal sources. Included in the review are slaframine; the hydroxylated indolizidines lentiginosine, swainsonine, castanospermine and their analogues; alkaloids from amphibians and marine sources; plumerinine; ipalbidine, phenanthroindolizidines and related alkaloids; lasubine-II: and lupin alkaloids. The literature from July 2001 to June 2002 is reviewed, and 142 references are cited.     

Indolizidine and quinolizidine alkaloids

This review covers the isolation, structure determination, synthesis and biological activity of indolizidine and quinolizidine alkaloids from microbial, plant and animal sources. Included in the review are slaframine; hydroxylated indolizidines and their analogues; alkaloids from ants and amphibians; metabolites of the genera Prosopis, Streptomyces and Nuphar and the Lythraceae; phenanthroindolizidines and related alkaloids; lupin alkaloids; and alkaloids from sponges. tunicates and coccinellid beetles. The literature from July 2000 to June 2001 is reviewed, and 172 references are cited.     

Stereoselective synthesis of (+)-(8R,8aR)-perhydro-8-indolizidinol

A highly stereoselective total synthesis of (+)-(8R,8aR)-perhydro-8-indolizidinol is described. Key steps involved in this synthesis are diastereoselective zinc allylation, azido-olefin cyclization and reductive amination followed by cyclization which effectively constructed the indolizidine ring. This contributes a unique approach to the synthesis of indolizidine alkaloids that offers the advantages of brevity and relatively high overall yields.     

A short route toward chiral, polyhydroxylated indolizidines and quinolizidines

In this paper, a rapid route toward functionalized bicyclic alkaloids is presented. In only three steps, an easily accessible carbohydrate derivative was converted into iodomethyl indolizidine 13, which can equilibrate to the corresponding iodoquinolizidine 15. We provide strong evidence that this equilibration proceeds via an aziridinium ion intermediate. Furthermore, nucleophilic substitution of the iodomethyl indolizidine as well as the aziridinium intermediate gives access to highly functionalized indolizidine and quinolizidine alkaloids.     

Efficient Synthesis of Indolizidine Alkaloids from γ-Hydroxy-α,β-unsaturated Sulfones

An efficient and stereoselective synthesis of polyhydroxylated indolizidine alkaloids from readily available N-substituted γ-hydroxyvinyl sulfones is described.     

A common approach to pyrrolizidine and indolizidine alkaloids; formal synthesis of (−)-isoretronecanol, (−)-trachelanthamidine and an approach to the synthesis of (−)-5-epitashiromine and (−)-tashiromine

A common and short stereoselective route is described for the formal synthesis of pyrrolizidine alkaloids, (−)-isoretronecanol and (−)-trachelanthamidine. An approach to the synthesis of indolizidine alkaloids (−)-5-epitashiromine and (−)-tashiromine utilizing ring closing metathesis is also described starting from commercially available and inexpensive l-proline.     

A stereoselective hydroamination transform to access polysubstituted indolizidines

Stereoselective, intramolecular, formal hydroamination of dienamines via directed hydroboration is reported. Four stereocenters are set in the process. Natural and unnatural indolizidine alkaloids can be synthesized from simple unsaturated amines using the title process.     

An unusual solvent effect in the cuprate displacement reaction of indolizidin-5-yl-methyl p-toluenesulfonate: stereoselective synthesis of indolizidine alkaloids

An unusual solvent effect in the cuprate displacement reaction of indolizidin-5-yl-methyl p-toluenesulfonate with dialkyl cuprates, derived from an alkyllithium and Grignard reagents, during the synthesis of indolizidine alkaloids 167B and 209D is described.     

A new synthetic method for an indolizidine skeleton by C-N bond formation via a pi-allylpalladium complex

Pd(0)-catalyzed intramolecular cyclic reaction via a pi-allylpalladium complex provided an indolizidine skeleton in satisfactory high and reproducible yields by using allylic compound having an acetoxyl group as a leaving group. These results must be available for syntheses of various functional indolizidine alkaloids.     

A New Asymmetric α-Amido-hydroxyalkylation Mediated by SmI_2

Polyhydroxylated indolizidine alkaloids, such as castanospermine (I) and swainsonine (II) are of longstanding interest due to their powerful glycosidase inhibitory activity. Asymmetric hydroxyalkylation via α-amido carbanions to form C-C bands would provide a convenient approach to these compounds. HO HO H OH H OH HO OH N N HO I II In continuation of our efforts in developing asymmetric α-amido-hydroxyalkylation method,1 we report a new SmI2 mediated flexible…     

Polyhydroxy alkaloids: chromatographic analysis

Polyhydroxy alkaloids are a burgeoning category of natural products that encompass several structural types and generally exhibit potent activity as inhibitors of glycosidases. As presently defined the group consists of monocyclic or bicyclic aLkaloids of the pyrrolidine, piperidine, pyrrolizidine, indolizidine and tropane classes, bearing two or more hydroxyl groups. These structural features render the compounds highly water soluble and frequently quite insoluble in non-hydroxylic solvents, so that their isolation and analysis by chromatographic means are consequently difficult. This problem is further confounded by the lack of a chromophore which would permit their detection by UV absorption. This review presents chromatographic techniques that have been successfully applied to the problem of isolating, purifying, detecting and analyzing polyhydroxy alkaloids.     

Concise synthesis of pyrrolidine and indolizidine alkaloids by a highly convergent three-component reaction

The synthesis of pyrrolidine and indolizidine derivatives through radical carboazidation of alkenes with α-iodoketones, followed by reductive amination, is described. When properly substituted, further lactamization afforded pyrrolizidinones in good yield. This carboazidation/reductive amination sequence was efficiently applied to the total synthesis of three different simple alkaloids, including (±)-monomorine I.     

Grandisine A and B, novel indolizidine alkaloids with human delta-opioid receptor binding affinity from the leaves of the Australian rainforest tree Elaeocarpus grandis

Two novel indolizidine alkaloids, grandisine A (1) and B (2), and the known alkaloid (-) isoelaeocarpiline (3) were isolated from the leaves of Elaeocarpus grandis and their structures determined by 1D and 2D NMR spectroscopy. The compounds showed affinity for the human delta-opioid receptor. Grandisine A contains a unique tetracyclic skeleton, while grandisine B possesses the unique combination of isoquinuclidinone and indolizidine groups in one molecule.     

Annulation of pyrrole: application to the synthesis of indolizidine alkaloids

The nucleophilicity of pyrrole has been exploited to rapidly assemble the bicyclic skeleton of the indolizidine alkaloids. The key sequence is the annulation of a second ring onto pyrrole from a γ-lactone and has been exploited in the synthesis of the natural products (±)-monomorine and (±)-indolizidine 209D.     

抗癌天然产物苦马豆素的合成研究进展

在过去十多年中, 多羟基吲哚兹定生物碱因其结构和多样性的生物活性(抗病毒、抗肿瘤、免疫调节活性)而引起了极大的关注. 其中最著名的成员是苦马豆素, 一种从灰苦马豆等植物中提取出来的化合物, 被证明具有治疗恶性肿瘤的作用并因此进行了大量合成研究. 到目前为止文献报道的合成方法都是基于碳水化合物原料或非碳水化合物底物和不对称反应. 尽管有些合成路线有效并且有实用价值, 但进一步开发制备天然或非天然吲哚兹定生物碱的通用和实用方法仍然非常重要. 总结了苦马毒素的合成研究进展, 以便为它的规模化生产提供思路和方法.     

Synthesis of alkylated indolizidine alkaloids via Pummerer mediated cyclization: synthesis of (±)-indolizidine 167B, (±)-5-butylindolizidine and (±)-monomorine I

The syntheses of indolizidine alkaloids, i.e., (±)-coniceine, (±)-indolizidine 167B, (±)-5-butylindolizidine and (±)-monomorine I via Pummerer cyclization are described. The key step is the transformation of lactam sulfoxide to bicyclic lactam via the Pummerer cyclization.     

Regio- and stereoselective ring opening of vinyl epoxides with MgBr2

The regio- and stereoselective ring opening of vinyl epoxides has been achieved by the use of Lewis acid, MgBr₂, affording bromohydrins in excellent yield, which are readily transformed to azidoalcohol, a key intermediate of several classes of pyrrolizidine and indolizidine alkaloids. The scope and limitations of the reaction are discussed.     

Synthesis of Strained γ‐Lactams by Palladium(0)‐Catalyzed C(sp3)−H Alkenylation and Application to Alkaloid Synthesis

A variety of strained α‐alkylidene‐γ‐lactams were synthesized by palladium(0)‐catalyzed intramolecular C(sp³)?H alkenylation from easily accessible acyclic and monocyclic bromoalkene precursors. These lactams are valuable intermediates for accessing various classes of mono‐ and bicylic alkaloids containing a pyrrolidine ring, as illustrated with the synthesis of an advanced model of the marine natural product plakoridine A and of the indolizidine alkaloid δ‐coniceine.