Alkaloids indolizidine

Digressing, we noted above that the other 1988 application of inverse-detected 2D NMR was to indolizine alkaloids of the pumiliotoxin-A and allopumiliotoxin classes (Edwards et al. 1988). A total of ten alkaloids were 

In 2006, Jung et al. reported another synthesis of (—)-lentiginosine (209) starting from the D-xylose-derived olefin 211 [72]. Subjection to chlorosulfonyl isocyanate (CSI) provided the allylic amine 212 with a high diastereoselectivity (syn/anti = 

4-methylmorpholine W-oxide acetone, HjO 2. i HCI (10%), dioxane ii Dowex 1x2 (OH )-form 

A different approach leading to ent-lentiginosine (77) was adopted by Schmidt et al. [73] who prepared pyrrolidine 214 in three steps from r-tartrate. N-Acyliminium ion-mediated allylation provided 215 in quantitative yield as a 

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Dieckmann reaction, 4, 471 Indolizidine alkaloids mass spectra, 4, 444 Indolizidine immonium salts reactions, 4, 462 Indolizi dines basicity, 4, 461 circular dichroism, 4, 450 dipole moments, 4, 450 IR spectra, 4, 449 reactivity, 4, 461 reviews, 4, 444 stereochemistry, 4, 444 synthesis, 4, 471-476 Indolizine, 1-acetoxy-synthesis, 4, 466 Indolizine, 8-acetoxy-hydrolysis, 4, 452 synthesis, 4, 466 Indolizine, I-acetyl-2-methyI-iodination, 4, 457 Indolizine, 3-acyloxy-cyclazine synthesis from, 4, 460 Indolizine, alkyl-UV spectra, 4, 449 Indolizine, amino-instability, 4, 455 synthesis, 4, 121 tautomerism, 4, 200, 452 Indolizine, 1-amino-tautomerism, 4, 38 Indolizine, 3-amino-synthesis, 4, 461, 470... 

Among the many recent applications to natural products, syntheses of pyrrolizidine and indolizidine alkaloids that take advantage of the 1,3-dipolar cycloaddition methodology have been reviewed [8]. The regio- and stereochemistry [9] as well as synthetic appHcations [10] of nitrile oxide cycloadditions have also been discussed. 

Molyneux, R. J. and James, L. F. 1982. Loco intoxication indolizidine alkaloids of spotted loco-weed Astragalus lentiginosus). Science 216 190-191. 

The product of the reaction in Entry 8 was used in the synthesis of the alkaloid pseudotropine. The proper stereochemical orientation of the hydroxy group is determined by the structure of the oxazoline ring formed in the cycloaddition. Entry 9 portrays the early stages of synthesis of the biologically important molecule biotin. The reaction in Entry 10 was used to establish the carbocyclic skeleton and stereochemistry of a group of toxic indolizidine alkaloids found in dart poisons from frogs. Entry 11 involves generation of a nitrile oxide. Three other stereoisomers are possible. The observed isomer corresponds to approach from the less hindered convex face of the molecule. 

Another Rhn-catalyzed decomposition of a a-diazoester as described by Sabe and coworkers [198] was used for the synthesis of indolizidine alkaloids (Scheme 6/2.8). It can be assumed that, first, an ammonium ylide is formed which then undergoes a 1,2-shift with ring-expansion. Thus, reaction of 6/2-40 with Rh2(OAc)4 led to a 72 28 mixture of 6/2-41 and 6/2-42 in 85 % yield. Cu(acac)2 can also be used with even better yields, but lower selectivity (65 35). 

An intramolecular palladium-catalyzed tandem cyclization of dienamides 67 in which the amide nucleophile adds twice has been developed (equation 29)60. This reaction constitutes a formal [4+1] cycloaddition and provides a new route to pyrrolizidine and indolizidine alkaloids. Reaction of dienamides 67 in the presence of catalytic amounts of Pd(OAc)2 and CUCI2/O2 as the oxidant afforded bicyclic compounds 68 in good yields. The pyrrolizidine derivative 68 (R = Me, n = 1) was transformed to the alkaloid ( )-heliotridane. 

Table 1 Structure of indolizidine alkaloids (bicyclic gephyrotoxins) synthesized since 1995...

Novel synthetic procedures for indolizidine alkaloids were developed via a samarium diiodide-promoted carbon-nitrogen bond cleavage as a key step. Application of the procedure led to the total synthesis of (+)-(8R, 8aR)-perhydro-8-indolizidinol <2006H193>. 

Several fully saturated derivatives that can be viewed as aza analogues of polyhydroxylated indolizidine alkaloids have also been prepared for their biological evaluation <2000JOC136, 2000T1005>. 

Indolizidine alkaloids. The key step in a new stereocontrolled synthesis of these alkaloids, such as castanospermine (5), depends upon the diastereoselective reaction of an azagluco aldehyde with allylmetal reagents catalyzed by Lewis acids (12, 21-22). Thus reaction of allyltrimethylsilane with the aldehyde 1 and TiCL, (excess) in CH2C12 at - 85° results in the product 2, formed by selective chelation of the ot-amino aldehydo group with TiCl4. The product can be converted into 5... 

The venom of ants of the genus Myrmicaria is made up of indolizidine or pyrrole-indolizidine alkaloids [188,189]. The synthesis of some of these alkaloids has already been reported in the review of Leclercq et al. [114]. Thus, we will report here only on the syntheses published since 1999. 

The functionalization of proline has been used to synthesize natural products from the indolizidine alkaloid family [71]. To this end, Lhommet and coworkers utilized... 

Both pyrrolizidine and indolizidine alkaloids can be synthesized by taking advantage of the anodic a-alkoxylation of Ai-alkoxycarbonylpyrroKdines (e.g. (131) to (132), Scheme 31). The method has been utilized to synthesize isoretronecanol (137), trachelanthamidine (138), elaeoka-nine A (135), and elaeokanine C (136) [57]. 

Once the methoxy group has been installed and nucleophilic capture of the intermediate has occurred, the product (132) can be treated with an enol ether (e.g. 133) and titanium tetrachloride to affect C-C bond formation adjacent to nitrogen. This sequence served nicely in syntheses of both indolizidine alkaloids elaeokanine A (135) and C (136). 

Swainsonine is a trihydroxylated bicyclic indolizidine alkaloid with four chiral centres, whose relative stereochemistry was determined by X-ray crystallographic analysis and the absolute configuration was deduced on the basis of biosynthetic and asymmetric induction studies, and then confirmed by an enantiospecific synthesis from D-mannose [2a]. 

Figure 2.13 The indolizidine alkaloid toxin swainsonine (a potent inhibitor of a-mannosidase), responsible for locoweed toxicosis.

Somfai s group has demonstrated that the aza-[2,3]-Wittig rearrangement of the viny-laziridines 134 to 135 is useful for the stereoselective construction of the indolizidine alkaloids 136 . ... 

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